Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
1
12
10.29228/jrp.97
981
Synthesis of some novel hydrazide-hydrazones derived from etodolac as potential anti-prostate cancer agents
Hande Cevher KOÇ
İrem ATLIHAN
Pınar MEGA-TİBER
Oya ORUN
Ş. Güniz KÜÇÜKGÜZEL
(R,S)-Etodolac [1,8-diethyl-1,3,4,9-tetrahydrapyrano(3,4-b)indole-1-acetic acid] is a nonsteroidal anti-inflammatory drug that contains carboxylic acid group with the structure of pyrano[3,4-b]indole. In this study, a series of novel (R,S)-Etodolac derivatives (3a-l) bearing hydrazide-hydrazone moiety were synthesized. The structures of these compounds were characterized by spectral (1H-NMR and FT-IR analyses) methods. All synthesized compounds were screened for anticancer activity against androgen-independent prostate adenocarcinoma (PC-3, DU-145) and androgen-dependent prostate adenocarcinoma (LNCaP) cell lines by using WST-8 colorimetric method. This method was used for cell viability and cytotoxicity analysis. Compound 3b (SGK-720) [2-(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetic acid[(2,6-dichlorophenyl)methylene]hydrazides] showed 10.36, 5.24, 15.53 μM anticancer activity against PC3, DU145, LNCaP cancer cell lines, respectively. According to JC-1 mitochondrial membrane potential test and Annexin V/PI staining, 3b was found to have apoptotic effect on these cancer cells. It is concluded that compound 3b containing 2,6-dichloro substituents may be one of the candidate molecules to cope with prostate cancer.
https://jrespharm.com/abstract.php?id=981
Etodolachydrazide-hydrazoneanticancer activityapoptosisWST-8 colorimetric method
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
13
19
10.29228/jrp.98
975
Synthesis and anticancer activity of new carbohydrazide derivatives bearing furan moiety
Fatih TOK
Elif KAYA TİLKİ
Miriş DİKMEN
Bedia KOÇYİĞİT-KAYMAKÇIOĞLU
In this study, some new carbohydrazide derivatives bearing furan moiety were synthesized. All carbohydrazide structures have been characterized by IR, 1H-NMR and elemental analysis. Anticancer activity of compounds were investigated on A549 human lung cancer and BJ normal fibroblast cells. According to the MTT assay results, all compounds demonstrated the cytotoxic activity on A549 cells with IC50 values of 43.38-342.63 μM except compound 3g. Only the IC50 values of compound 3c was below 400 μM on BJ cells. Especially, compound 3e showed significant anticancer effects on A549 cells with IC50 value of 43.38 μM and also didn’t show cytotoxic effects on normal BJ cells.
https://jrespharm.com/abstract.php?id=975
Amidefurananticancercarbohydrazide
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
20
27
10.29228/jrp.99
984
Novel substituted oxadiazole - piperazine derivatives as potential mao inhibitors: design, synthesis, in vitro and in silico studies
Harun USLU
Begüm Nurpelin SAĞLIK
Derya OSMANİYE
Kadriye BENKLİ
Recent studies have shown that there are many piperazine and oxadiazole derivatives with MAO-A and/or MAO-B inhibitory activity. For this reason in our recent study, a new compound series of oxadiazole - piperazine derivatives (4a-e) were designed, synthesized, characterized and screened their hMAOs inhibitory activities. When the in silico studies were examined, it was seen that the pharmacokinetic properties and interactions with the receptor of synthesized compounds were suitable. Compound 4e, with a NO2 group on the 4-position of the phenyl ring, found showing significant MAO-A inhibitory activity. Compound 4e, was the most effective agent against MAO-A enzyme with IC50 value of 0.116 ± 0.004 μM. The newly synthesized oxadiazole - piperazine derivatives appears to be supported studies to design MAO inhibitors to obtain more suitable drugs, against diseases such as depression and anxiety due to MAO-A.
https://jrespharm.com/abstract.php?id=984
hMAOs inhibitionoxadiazolepiperazineADMEmolecular docking
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
28
34
10.29228/jrp.100
980
Synthesis and antimicrobial activity of [1,2,4]triazіno[2,3-c]quinazoline – pyrazoline hybrids
Inna NOSULENKO
Galyna BEREST
Dmytro SKORYNA
Oleksii VOSKOBOINIK
Serhii KOVALENKO
Present manuscript describes the design, synthesis and antimicrobial activity of novel [1,2,4]triazіno[2,3-c]quinazoline – pyrazoline hybrids. The combination of pyrazoline cycle with [1,2,4]triazіno[2,3-c]quinazoline heterocyclic fragment was substantiated as promising approach for development of novel antibacterial and antifungal agents. The simple and effective synthetic procedure for target heterocyclic hybrids was proposed. The structures of obtained compounds were verified by appropriate physicochemical methods, the features of 1H NMR-spectral characteristics were described as well. It was shown that synthesized compounds reveal significant growth inhibitory activity against Candida albicans strain.
https://jrespharm.com/abstract.php?id=980
quinazolinepyrazolineheterocyclic hybridsantimicrobial activityCandida albicans
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
35
43
10.29228/jrp.101
982
Role of nitrogen containing heterocyclic compounds in acyl co-a carboxylase carboxyltransferase: docking with dynamic simulation studies
Manjiri D. BHOSALE
Asha B. THOMAS
Kiran Bharat LOKHANDE
Kakumani Venkateswara SWAMY
Sohan S. CHITLANGE
Acyl Co-A carboxylase carboxyltransferase (AccD5) is essential for cell wall lipid biosynthesis and its disruption leads to mycobacterial death. Acyl CoA is the key regulation point for fatty acid synthesis and therefore AccD5 has become a good target for mycobacterial disease. Herein, docking and Molecular dynamic simulations with other computational techniques and softwares has been used to select the best compound. The heterocyclic compounds were indole, n-methylpiperazine, piperidine, and pyrrolidine derivatives. Among which, the docking results showed Ib5, an indole containing heterocyclic compound, as a potent inhibitor with good binding affinity with -20.23 kcal/mol of energy as compared with the standard NCI-65828 (8-amino-5-(4’-hydroxybiphenyl-4ylazo)naphthalene-2-sulfonate molecule with -19.24 kcal/mol of binding energy. Additionally, MD simulations showed less fluctuations with depiction of root means square deviation and root mean square fluctuation graphs in 2A7S-Ib5 complex. Wherein, this molecular modeling of AccD5 with Ib5 provided an insight to use it as an anti-tubercular drug. Therefore, this method has helped to prove the nitrogen containing heterocyclic compounds can be used against Mycobacterium tuberculosis.
https://jrespharm.com/abstract.php?id=982
Anti-tubercularAccD5Acyl Co-A carboxylasecarboxyltranferasemolecular dockingmolecular dynamic simulation
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
44
51
10.29228/jrp.102
1006
Protective effect of mangiferin on doxorubicin-induced liver damage in animal model
Fauzul HUSNA
Wawaimuli AROZAL
Hanifah YUSUF
Safarianti SAFARIANTI
Mangiferin is a bioactive compound which has antioxidant effect, but its effect on liver protection during chemotherapy with doxorubicin is understudied. The objective of this study was to assess the protective effect of mangiferin on liver injury induced by doxorubicin. The doxorubicin was injected intraperitoneally at a total dose of 15 mg/kg b.w, and then the animals were orally supplemented with mangiferin (either 50 and 100 mg/kg b.w) for five weeks. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), the level of malondialdehyde (MDA) and glutathione, and liver histopathology were examined to evaluate the liver damage. The results showed that doxorubicin could cause liver cell damage to the rats. In addition, the study revealed that the supplementation of mangiferin (50 and 100 mg/kg b.w) decreased ALT and AST activities, as well as lipid peroxidation. It also increased SOD and GSH levels of liver cells (p <0.05). Our study proved that the improvement in liver function and oxidative stress parameters caused by doxorubicin, indicates that the mangiferin has a protective effect against liver damage induced by doxorubicin.
https://jrespharm.com/abstract.php?id=1006
Antioxidantdoxorubicinhepatotoxicitymangiferinoxidative stress
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
52
62
10.29228/jrp.103
952
Protective effect of edaravone on rat testis after valproic acid treatment
Cagri CELIK
Bertan Boran BAYRAK
Neziha HACIHASANOGLU CAKMAK
Refiye YANARDAG
Valproic acid (n-dipropyl-acetic acid, VPA) is a medication used as anticonvulsant in the treatment of bipolar disorder, and for migraine prophylaxis. Long-term use of VPA is known to trigger reproductive impairment, which is mediated by elevation of testicular oxidative stress. Edaravone is used in the treatment of cerebrovascular diseases. It can diffuse into many disease-affected organs, thus shows protective effects in numerous tissues including the heart, lung, and testis. The main goal of the present study was to determine the possible protective role of edaravone against VPA-induced oxidative testicular injury. Male Sprague Dawley rats were assigned into four groups. Control rats; rats given only edaravone (30 mg/kg/day); rats given only VPA (500 mg/kg/day); rats given VPA+edaravone for seven days. Edaravone and VPA were applied intraperitoneally. After eight days, testicular tissues were taken from rats. There was a statistically significant increase in the levels of reduced glutathione, lipid peroxidation, reactive oxygen species, total oxidant status, oxidative stress index, and DNA contents as well as catalase, superoxide dismutase, glutathione-related enzymes, gamma-glutamyl transferase, acid and alkaline phosphatases, lactate dehydrogenase, myeloperoxidase and sorbitol dehydrogenase activities in VPA group. More so, advanced oxidized protein products, protein carbonyl, and nitric oxide levels were also significantly increased in VPA group. Activities of glucose-6-phosphate dehydrogenase and sodium/potassium ATPase and total antioxidant status levels remarkably decreased in VPA given group. Treatment with edaravone to VPA group significantly reverted these alterations. These findings demonstrate that administration of edaravone has a beneficial effect against testicular injury in VPA-induced oxidative stress.
https://jrespharm.com/abstract.php?id=952
Edaravonetestis injuryvalproic acidoxidative stress parametersantioxidant enzymes
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
63
74
10.29228/jrp.104
968
Evaluation of anti-inflammatory, immunomodulatory effects and celiac-like side effect of olmesartan medoxomil as a vitamin d receptor agonist and angiotensin ii receptor blocker
Yelda KOMESLİ
Ercument KARASULU
Prodrug Olmesartan Medoxomil (OM) is an angiotensin II receptor blocker (ARB) and a vitamin D Receptor (VDR) agonist. Reducing the inflammation and improving the immune system OM prevents organ damage. Angiotensin II receptor blockers (ARBs) can raise serum and tissue levels of the membrane-bound form of monocarboxypeptidase angiotensin converting enzyme 2 (ACE2). Increased ACE2 activity causes the balance in the RAAS to shift towards the positive ACE2-Ang-(1-7). Therefore It can be useful with anti-inflammatory, anti-fibrotic and anti-oxidative stress signals in the treatment of immune system diseases. OM is also known to have adverse effects, such as celiac-like enteropathy which was accepted by the FDA. The mechanism of OM's intestinal injury is thought to be the excessive consumption of the enzymes POX1 and carboxymethylenebutenolidase, which are also responsible for the the digestion of gliadin during the hydrolysis of the drug. Cell-mediated immune response and genetic predisposition are the other factors. Our histopathological findings of olmesartan-induced celiac-like enteropathy in rat intestines were increased mononuclear cell infiltration and villous atrophy. In this study these various action mechanisms of OM and its possible immun system booster effects were discussed. The findings of our rat intestines after exposure to OM-Suspension supported and correlated clinical findings of OM. In conclusion, by making extensive evaluations, OM can be a promising immunomodulator agent in immune system diseases.
https://jrespharm.com/abstract.php?id=968
ARBvitamin-DVDR-agonistACE2Ang-(1-7)PON1celiac-like-enteropathyimmunotherapeutic
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
75
87
10.29228/jrp.105
979
Formulation, characterization, and in vitro release studies of modified release multiple unit particulate system (mups) of venlafaxine hydrochloride
Isaiah BOYAPATI
Rajendra AWASTHI
Giriraj T. KULKARNI
Multiple unit particulate system (MUPS) is more recent, challenging, effective and attractive option for the pharmaceutical industries that gives an efficient way to deliver drugs in modified pattern. This study aimed to improve the release profile of venlafaxine hydrochloride by developing modified release MUPS using polyvinyl pyrrolidone K-30, ethyl cellulose 20 cps and Hypromellose E 5LV. Preliminary trials were carried out to select the inert carrier, binder, and viscosity grade of rate controlling polymers. Further, optimization of binder concentration and extended-release coating was carried out. The formulation development of MUPS was divided into two categories as (i) drug layering on inert carrier, i.e., sugar spheres and (ii) extended-release coating. Comparative multimedia dissolution study of venlafaxine hydrochloride extended-release capsules was carried out and compared with the marketed formulation to ascertain the in vitro drug release behavior. XRD study indicated conversion of monohydrate form of venlafaxine hydrochloride and remained unaffected during storage. SEM images confirmed smooth surface of MUPS without any pores. The coated spheres had more dense surface compared to the uncoated pellets. Hypromellose E 5 LV showed better binding properties. Ethyl cellulose (20 cps) showed sustained release profile. The blend containing ER – I spheres (10% coating) and ER – II spheres (11% coating) at 60: 40 ratio showed dissolution profile similar to that of the innovator product. The formulated venlafaxine hydrochloride loaded MUPS filled in hard gelatin capsule can open a new avenue for the delivery of therapeutics with improved potential.
https://jrespharm.com/abstract.php?id=979
Extended releasemultiple unit particulate systemmultimedia dissolutionpolymorphismsugar spheres
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
88
101
10.29228/jrp.106
974
Development and radiolabeling of lipid nanoparticles with [<sup>99m</sup>tc]tc-hmpao: characterization, stability, cytotoxicity and cell binding studies
Evren ATLIHAN-GÜNDOĞDU
Meliha EKİNCİ
Emre ÖZGENÇ
Emine Selin DEMİR
Derya İLEM-ÖZDEMİR
In this study, we aimed to develop new lipid based nanoparticles (LPNs) and radiolabeled LPNs with [<sup>99m</sup>Tc]Tc-HMPAO to investigate its cell binding capacity comparatively with [sup>99m</sup>Tc]Tc-HMPAO on different cancer cells. According to obtained results, LPNs with zeta potential of -27.4 ± 0.95 mV, particle size of 93.5 ± 1.17 nm, and polydispersity index of 0.35 ± 0.04 were successfully developed. The optimum radiolabeling efficiency was found to be above 90% at 15-min of incubation time. The cell binding capacity of [<sup>99m</sup>Tc]Tc-HMPAO-LPNs was found to be higher than [<sup>99m</sup>Tc]Tc-HMPAO in cancer cell lines. The results demonstrated that [<sup>99m</sup>Tc]Tc-HMPAO-LPNs may be a promising agent for cancer diagnosis alternatively to [<sup>99m</sup>Tc]Tc-HMPAO.
https://jrespharm.com/abstract.php?id=974
Lipid nanoparticlesradiopharmaceuticalsHMPAOcell bindingcancer diagnosis
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
102
111
10.29228/jrp.107
1004
The microencapsulation of oregano extract by using different techniques: spray-drying and freeze-drying techniques and their in vitro characterization
Juste BARANAUSKAITE-ORTASÖZ
Burcu ÜNER
Gülengül DUMAN
Çetin TAŞ
The potential antimicrobial and antioxidant benefit of high levels of ursolic, rosmarinic acids and carvacrol in oregano extract has been limited until now by poor bioavailability arising from the low aqueous-phase solubility and slow dissolution behavior of the freeze-dried extract. To address this issue, microencapsulation technique had been used to solve above mentioned problems and to protect active substances from deteriorating due to environmental conditions, such as moisture, oxidation. The experimental settings were performed by statistical mixture experimental design. Moreover, microcapsules and freeze-dried extract were compared to ascertain the merit of microcapsules as a carriers for these poorly aqueous-soluble compounds. When the wall material solution contained 1.43 g of maltodextrin, 4.17 g of gum arabic, 14.39 g of modified starch, and 20 g of ethanol oregano extract, the yield of oregano’s active compounds, ursolic, rosmarinic acids and carvacrol, were 0.98 mg/g, 3.38 mg/g and 3.38 mg/g respectively. In particular, the release profile of ursolic, rosmarinic acids and carvacrol had levelled off after 15 minutes, depicting an impressive 2.7- 3.0 fold increase compared to the freeze-dried control extract. The results imply that all actives can be conveniently delivered via oral and mucosal routes by first internalizing oregano extracts into appropriately engineered microcapsules.
https://jrespharm.com/abstract.php?id=1004
Microencapsulationspray-dryingfreeze-dryingOreganoin vitro dissolution data
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
112
122
10.29228/jrp.108
957
Development and validation of an hplc method for the determination of hyaluronic acid active substance in pharmaceutical formulations
Emre Şefik ÇAĞLAR
Neslihan ÜSTÜNDAĞ OKUR
Hatice Yeşim KARASULU
It is an analytical requirement to identify and determine high molecular weight APIs in pharmaceutical forms. For this reason, it is aimed to develop and validate an analytical method for the determination of hyaluronic acid in pharmaceutical form in this study. 0.1 M Na2SO4 was prepared as mobile phase. The separation of compound was performed with a OHpak Shodex SB-806M HQ (13 μm, 8,0 x 300mm, Japan) analytical column. Guard column which is OHpak SB-G, (8 μm, 100 Å, 6.0 x 50 mm, Japan) was integrated to the system before the analytical column. UV detection at 198 nm was used to monitor the eluent and flow rate of the mobile phase was set to 1 mL/min. The method has been validated in terms of system suitability, linearity, limits of detection (LOD) and quantity (LOQ), precision, accuracy, specificity, selectivity, and stability. The obtained findings showed that the analytical method has linearity higher than 0.99, accuracy, precision, selectivity and stability. The method was found to be precise, accurate and specific during the study.
https://jrespharm.com/abstract.php?id=957
Hyaluronic acidHPLC-UVmicroemulsionanalytical methodvalidation
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
123
135
10.29228/jrp.109
998
A new reliable and rapid hplc method for the simultaneous determination of amoxicillin and sulbactam pivoxil in pharmaceuticals. application to both assay and dissolution samples
Mariela Fernanda RAZUC
Fernanda Anabel CABRERA
Mariano Enrique GARRIDO
María Verónica RAMIREZ-RIGO
A fast, efficient and simple high performance liquid chromatographic method was developed and validated for the simultaneous determination of amoxicillin trihydrate (AMO) and sulbactam pivoxil (SP) in oral pharmaceutical dosage forms and, eventually, for their dissolution tests. The difference in molar absorptivities of these compounds constituted an analytical challenge, especially in formulations where AMO was in a higher proportion than SP. A reverse phase C18 column was used with a mobile phase consisting of acetonitrile and water (80:20 v/v) in isocratic mode. The retention times were found to be 2.26 min and 1.34 min for SP and AMO, respectively. The linearity range was evaluated over the concentration range of 2.5 and 250.0 μg mL<sup>-1</sup> (correlation coefficients higher than 0.9998). The method was validated according to the International Conference on Harmonization ICH guidelines regarding selectivity, linearity, accuracy, precision, limit of detection, limit of quantification, system suitability and robustness. The validated method was applied for the quantification of AMO and SP in commercial tablets and oral suspensions (AMO/SP ratio between 1:1 and 7:1), being the first method in the open literature that enables the correct quantification of both active ingredients in formulations with an AMO/SP ratio higher than 1:1. Also, the new method was successfully applied for the dissolution study of AMO/SP formulations, which was reported for the first time in the open literature. According to the obtained results, the proposed method can be applied in the quality control of pharmaceuticals containing a combination of amoxicillin and sulbactam pivoxil.
https://jrespharm.com/abstract.php?id=998
Amoxicillin trihydratesulbactam pivoxilHPLCmethod validationdissolutionoral pharmaceutical dosage forms
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
136
144
10.29228/jrp.110
997
Analysis of 3-hydroxyisovaleric acid and 3-hydroxybutyric acid in plasma samples by lc-ms/ms
Tuba REÇBER
Ece ÖZKAN
Emirhan NEMUTLU
Mehmet Sinan BEKSAC
Sedef KIR
Down syndrome is a common genetic disorder that results from the presence of an extra chromosome in the 21<sup>st</sup> chromosome pair of humans. Metabolomics is an alternative method in discovery of new biomarkers for the screening and diagnosis of Down syndrome. In this study, quantitative analyzes of 3-hydroxybutyric acid and 3-hydroxyisovaleric acid, selected as possible markers for prenatal diagnosis of Down syndrome were performed. LC-MS/MS analyzes were performed on a Phenomenex Luna NH<sub>2</sub> (100 x 4.6 mm, 3 μm) column using a mobile phase mixture of 0.1% formic acid and acetonitrile containing 0.1% formic acid at a flow rate of 0.35 mL/minute. The MRM transitions were 103.0→59.0 for 3-hydroxybutyric acid and 117.1→59.0 for 3-hydroxyisovaleric acid. Under these conditions, the retention times of 3-hydroxyisovaleric acid 3-hydroxybutyric acid were 2.7 and 3.1 minute, respectively. The method was found linear from 0.1 to 10.0 μg/mL for both metabolites. The limit of detection (LOD) was 0.017 μg/mL for 3-hydroxybutyric acid and 0.003 μg/mL for 3-hydroxyisovaleric acid. The lower limit quantification (LLOQ) was 0.045 μg/mL for 3-hydroxybutyric acid and 0.008 μg/mL for 3-hydroxyisovaleric acid. The method has been proven to be selective, precise, accurate, sensitive, and robust based on the validation studies results. Finally, the method was applied to plasma samples of the pregnant women with healthy fetus (n = 30) and with Down syndrome fetus (n = 17). As a result of the analysis, a statistically significant increase (p <0.01) was observed in the 3-hydroxybutyric acid level of the group with Down syndrome compared to the healthy group. This result strengthens the use of 3-hydroxybutyric acid as an important biomarker in the prenatal screening/diagnosis of Down syndrome.
https://jrespharm.com/abstract.php?id=997
Down syndromeprenatal screeningmetabolomicsliquid chromatography-tandem mass spectrometry (LC-MS/MS)3-hydroxyisovaleric acid3-hydroxybutyric acid
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
145
153
10.29228/jrp.111
955
Antihyperglycemic and neuroprotective activity of adenanthera pavonina bark against streptozotocin induced diabetic rats
Alagiri ABARNADEVIKA
Kumarasamy KAVITHA
Kasiramar GOPALASATHEESKUMAR
Worldwide diabetes and diabetic neuropathy is the highly prevalent healthcare problem. Herbal based therapy is an alternative and safe management of this problem. Adenanthera pavonina is an important medicinal plant having many of the medicinal values. This research aimed to evaluate the antihyperglycemic and neuroprotective activity of bark of Adenanthera pavonina. Hydro alcohol (50% methanol) was used as the solvent for extraction. Streptozotocin (55 mg/kg, i.p) induced diabetic rats were used for the evaluation of antihyperglycemic and neuroprotective activity. Diabetic rats were treated with hydro alcoholic bark extract of Adenanthera pavonina (HABEA) for 21 days. After treatment period blood glucose levels, SGOT, SGPT, Glutamate and Lipid peroxidase levels were decreased significantly in HABEA (200 and 400 mg/kg, p.o) treated rats. However, body weight, Serotonin, GABA, total protein and reduced glutathione levels were increased. And also behavioral parameter such as pain behavior (Hot Plate Method and Tail Immersion Method) and locomotor behavior (actophotometer) were significantly improved in HABEA (200 and 400 mg/kg, p.o) treated rats. These are the findings confirms that, the HABEA has significant antihyperglycemic and neuroprotective activity. Alkaloids, glycosides, flavonoids, saponin, phenolics and phytosterol present in the bark of Adenanthera pavonina may be the reason for its antihyperglycemic and neuroprotective activity. Further, this research will useful for the isolation of active principles from HABEA and determining its molecular mechanisms.
https://jrespharm.com/abstract.php?id=955
Diabetesglutamatebehavioralherbal medicinediabetic neuropathy
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
154
162
10.29228/jrp.112
958
Extracts of portulaca oleracea l. growing in kashmir valley exert apoptosis mediated antiproliferative effects and inhibit migration and invasion of oral cancer cells
Aadil KHURSHEED
Vikrant JAIN
The main aim of this research was to investigate the antiproliferative effects of P. oleracea L. extracts against oral cancer cells and the underlying mechanism of action. The effects of extracts on SCC-9 cell proliferation and colony generation were monitored by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and clonogenic assay, respectively. Morphological features were studied by phase-contrast microscopy. Apoptotic studies were carried out through AO/EB (Acridine Orange/Ethidium Bromide) staining and western blotting assay. Cell migration and invasion abilities of SCC-9 cells were studied by transwell assay. The results indicated that aqueous, ethanolic and hexane extracts all showed significant (P<0.05) proliferation inhibition against SCC-9 cells. However, a significant IC50 value was determined in case of ethanolic extract that is 52 μg/ml. The number of colonies reduced remarkably post extract treatment. Treated cells showed disturbed morphological features pointing towards apoptotic cell death. It was observed that ethanolic extract caused nuclear disintegration and membrane damage indicated apoptotic cell death, which was further supported by western blotting revealing increased expression of Bax and decreased Bcl-2 expression in treated SCC-9 cells. Furthermore, ethanolic extract significantly blocked the potency of SCC-9 cell to migrate and invade. In conclusion, the results showed that P. oleracea L. possess strong antiproliferative effects against oral cancer cells SCC-9 mediated via apoptosis induction. Moreover, migration and invasion of SCC-9 cells was also inhibited significantly. Therefore, our research could prove beneficial in oral cancer research and treatment and also could help in finding lead drug candidates from P. oleracea.
https://jrespharm.com/abstract.php?id=958
Oral cancerPortulaca oleraceaapoptosisproliferationcell migrationcell invasion
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
163
173
10.29228/jrp.113
967
In vitro antiproliferative, antioxidant, anti-inflammatory activities and phenolic profile of centaurea saligna (k.koch) wagenitz
Aybeniz YILDIRIM
Ali ŞEN
Fatih GÖĞER
Özlem BİNGÖL ÖZAKPINAR
Leyla BİTİŞ
In this study, methanol extract (CSM) and their hexane (CSH), chloroform (CSC), ethyl acetate (CSEA) and aqueous methanol fractions (CSAM) prepared from aerial parts of Centaurea saligna (K.Koch) Wagenitz were investigated for in vitro antiproliferative, anti-inflammatory and antioxidant activity. Anticancer, antioxidant, anti-inflammatory activities of these extracts were carried out by MTT, DPPH-ABTS, 5-lipoxygenase methods, respectively. Methanol extract and its fractions of C. saligna were evaluated for their cytotoxicity against MCF-7, A549, HeLa, HT-29, PC-3 cell lines at a concentration of 50 μg / ml. Total flavonoid and phenolic contents of extracts were detected by AlCI3 and Folin-Ciocalteu methods, respectively. Analysis of phytochemical of CSEA, showing a strong anti-inflammatory activity with good antioxidant activity, was performed by LC-MS/MS. CSC exhibited the best antiproliferative activity against HeLa, HT-29, MCF-7 cell lines with 50.18%, 46.88%, 45.42% mortality, respectively. CSEA showed the highest antioxidant activity with IC50 values of 82.05 μg/ml and 108.4 μg/ml against ABTS and DPPH radicals, respectively. The highest total phenolic amounts have been determined in CSEA with value of 379.2 mg GAE/g extract. In the same way, the highest total flavonoid amounts have been observed in CSEA with values of 170.3 mg QE/g extract. CSEA showed strong anti-inflammatory activity with IC50 value of 0.10 μg/ml when compared to indomethacine as standard (22.39 μg/ml). Analysis of CSEA by LC-MS/MS revealed that the major compounds were quinic acid, 5-caffeoylquinic acid, apigenin C-hexoside-C-pentoside, p-coumaroylquinic acid, quercetin glucoside, di-caffeoylquinic acid, isorhamnetine glucoside, isorhamnetin glucuronide and isorhamnetin derivative. These results proved that CSEA has significant anti-inflammatory and antioxidant activity and CSC has good antiproliferatif activity. Also, the results demostrate that CSEA and CSC are a good source for further bioactivity-guided isolation in discovering new active antioxidant, anti-inflammatory and antiproliferative compounds.
https://jrespharm.com/abstract.php?id=967
Centaurea salignaantioxidant activityantiproliferative activityanti-inflammatory activity
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
174
179
10.29228/jrp.114
951
Fatty acids and antioxidant capacities of three centaurea l. species
Pelin TAŞTAN
Burcu TÜZÜN
Bijen KIVÇAK
Tuğçe FAFAL
The aim of this study is to determine the fatty acid compositions and antioxidant activities of three Centaurea species as Centaurea iberica, C. urvillei ssp. hayekiana, and C. urvillei ssp. nimrodis and compare them with each other. As a result of fatty acid determination by GC MS method, oleic acid and linoleic acid were found as the main fatty acids in these Centaurea species. Polyunsaturated fatty acids (PUFAs) were determined at 58.66%, 46.98%, 62.22% in C. iberica, C. urvillei ssp. hayekiana and C. urvillei ssp. nimrodis, respectively. Antioxidant activities of methanolic extracts of three Centaurea species were evaluated by DPPH, ABTS and CUPRAC assays. The methanol extract of C. urvillei ssp hayekiana showed the highest antioxidant activity in direct proportion to the total amount of phenolic and flavonoid substances. The fact that the antioxidant activities of these three species and fatty acid analyzes have not been compared in previous studies is important in that this study is the first.
https://jrespharm.com/abstract.php?id=951
Fatty acidCentaurea ibericaC. urvillei ssp. hayekianaC. urvillei ssp. nimrodisantioxidant activity
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
180
188
10.29228/jrp.115
1005
Protective effect of enhydra fluctuans dc. aerial against insulitis in alloxan-induced diabetic rats
Rina DELFITA
Dahelmi DAHELMI
Djong Hon TJONG
Suhatri SUHATRI
This study aimed to assess the protective effect of the n-hexane fraction of Enhydra fluctuans aerial against insulitis in alloxan-induced diabetic rats. A total of 30 male rats (five normal rats and 25 diabetic rats) were assigned to one of six groups (n = 5/groups): group 1 is the normal rat group (GN) was without treatment, group 2 is diabetic rat was given 0.5% Na-CMC (G0), group 3 is diabetic rat was given glibenclamide 0.45 mg/kg body weight (G1), group 4, 5, and 6 are diabetic rats were given n-hexane fraction doses of 57.03, 114.06, and 171.09 mg/kg body weight respectively. The experiment was carried out over 21 days. Blood glucose was measured on the first and latest day of treatment. Furthermore, insulin levels, the number of pancreatic β-cell, and degrees of insulitis were evaluated. The n-hexane fraction reduced blood glucose, increased insulin levels, and increased the number of pancreatic β-cell significantly in alloxan-induced diabetic rats. The administration of the n-hexane fraction at a dose of 57.03 mg/kg body weight exerted the best protective effect against insulitis and promoted regeneration of the islet of Langerhans. The results of this study indicate that this herb could effectively reduce insulitis and promote the regeneration of pancreatic tissue under diabetes. Thus, E. fluctuans has the potential to be developed as a novel diabetes drug.
https://jrespharm.com/abstract.php?id=1005
AlloxanantidiabetesEnhydra fluctuanshyperglycemiainsulitis
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
189
197
10.29228/jrp.116
956
The study of the anti-inflammatory activity of a stomatological gel based on an extract of artemisia scoparia waldst. et kit
Dmitry POZDNYAKOV
Emma AYRAPETYAN
Dmitry KONOVALOV
The objectives of present investigation is to study of the pharmacology activity of a stomatological gel
based on an extract of Artemisia scoparia. Ethanol extract of Artemisia scoparia contains chlorogenic acid, scopoletin,
umbelliferone and scoparone which have anti-inflammatory activity. Kamistad gel was used as a comparison.
Researches show wormwood-based gel has a local anti-inflammatory effect, comparable to that of the reference drug -
Kamistad.
https://jrespharm.com/abstract.php?id=956
Artemisia scopariaanti-inflammatory activitystomatological gelanimalswormwood
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
198
209
10.29228/jrp.117
983
Characterization and evaluation of the antimicrobial properties of algal alginate; a potential natural protective for cosmetics
Selin SAYIN
Tolga DEPCI
Mehmet NAZ
Selda SEZER
Merve Gökşin KARAASLAN
Aycan ARAS
Sinem UĞUR
Zafer ÇETİN
Eyüp İlker SAYGILI
Burhan ATEŞ
Sargassum vulgare was sampled by free dives in Iskenderun Bay, Hatay, Turkey, in September 2018. Sargassum vulgare is a material with high economic value because it has compounds that can be used in medical applications such as alginic acid and at the same time it contains carbohydrates and vitamins. Alginates were extracted with a sequential extraction protocol from Sargassum vulgare. Structural characterization of alginate obtained from Sargassum vulgare was determined by FT-IR spectrum, phase structure by XRD diffractometer, and surface morphology by SEM image. Within the scope of the study, alginate obtained from Sargassum vulgare and herbal preservative 705 used in the field of cosmetics were compared. After pretreatment of Sargassum vulgare with ethanol, alginate extraction was performed. Microorganisms of Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, Escherichia coli, Aspergillus brasiliensis were used to examine the antimicrobial activity of the obtained alginate and showed that the contamination risk was tolerable for all microorganisms examined on the seventh day of incubation. Alginate obtained from Sargassum vulgare was found to be more effective than herbal preservative 705 at 0 hours. Pseudomonas aeruginosa, Staphylococcus aureus are microorganisms with the highest effect in the 0 hour. Since alginate obtained from Sargassum vulgare is more effective on microorganisms in a shorter time than herbal preservative 705, it is predicted that it can be a product that can be used in the field of cosmetics.
https://jrespharm.com/abstract.php?id=983
Sargassum vulgarealgaeantimicrobial activityalginatesnatural cosmetics
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
210
218
10.29228/jrp.119
1007
Development and in-vitro characterization of l-cysteine loaded alginate beads for oral delivery
Kıvılcım ÖZTÜRK
The purpose of this work is to develop a biodegradable calcium alginate (Ca-alginate) bead formulation to provide controlled release of l-cysteine (Cys) amino acid for oral drug delivery. Ca-alginate bead formulations were prepared successfully and reproducibly using calcium chloride as a cross-linking agent. The beads were then evaluated in terms of morphology, particle size, swellability, thermal behaviors, encapsulation efficiency, and in-vitro drug release at pH 1.2 and pH 7.4. The size of the beads was measured between 2.230.11 and 2.410.12 mm. In terms of thermal analysis, differential scanning calorimetry was utilized to ensure the encapsulation of Cys into bead formulation. Cys encapsulation was determined as 79.49 %1.12. Swelling index of blank beads were found to be in a range of 0.31-0.35 in HCl solution at pH 1.2; 0.98-1.08 in PBS buffer at pH 7.4. Alginate beads exhibited controlled release, followed the Weibull model which is consistent with the swelling pattern. The physico-chemical properties of the developed formulation indicate that the formulation is suitable for oral Cys delivery.
https://jrespharm.com/abstract.php?id=1007
Ca-alginate bead, sodium alginateoral drug deliveryl-cysteinecontrolled release
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
219
230
10.29228/jrp.120
1009
A new perspective for biological activities of novel hexahydroquinoline derivatives
Gökalp ÇETİN
Busra ÇETİN
Betül ÇOLAK
Melih AŞAN
Gökcen BİRLİK DEMİREL
Demet CANSARAN-DUMAN
Nefise AKÇELİK
Rahime ŞİMŞEK
Cancer is a systemic disease that occurs by various molecular mechanisms and its certain treatment has not been achieved yet. Antimicrobial drugs are the only option for the treatment of infections cause by bacteria and fungi. However, most microorganisms might develop resistantance against these drugs. 1,4-Dihydropyridine (1,4-DHP) is a partially saturated form of pyridine ring which shows calcium channel modulator activity. In addition to this activity of 1,4-DHPs and analog compounds such as hexahydroquinoline (HHQ), other activities have also been investigated. In this study, two new HHQ derivatives were synthesized to obtain a lead compound which has anticancer and antimicrobial activity. The structures of the synthesized compounds were proved by spectral methods. These HHQ derivatives compounds were conjugated to magnetic nanoparticles to investigate the changes in their anticancer and antimicrobial activities. For this purpose, firstly, we synthesized silica-coated magnetic nanoparticles. The silica-coated magnetic nanoparticles were conjugated with HHQ to enhance anticancer and antimicrobial activities. Anticancer and antimicrobial activity studies were carried out for both compounds and magnetic nanoparticle (MNP) forms. In addition, the physicochemical and pharmacokinetic properties, lipophilicity, water solubility and druglikeness of the compounds were determined in silico. Altogether, our data indicate that the new hexahydroquinoline derivatives have anticancer activity and the magnetic nanoparticle form led to increasing to this activity.
https://jrespharm.com/abstract.php?id=1009
Hexahydroquinolinemagnetic nanoparticle (MNP)anticancerantibacterialantifungalsynthesisspectraHantzsch reaction
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
1
231
242
10.29228/jrp.121
1012
Design, synthesis and bioactivity studies of novel triazolopyrimidinone compounds
Huseyin ISTANBULLU
Gulsah BAYRAKTAR
Ismail OZTURK
Gunes COBAN
Merve SAYLAM
This study was aimed to develop novel compounds to combat antimicrobial resistance, which is one of the biggest threats to global health. For this purpose, compounds bearing triazolopyrimidinone ring and N-(methylnaphthalene)piperazine (NMP) hybrids were designed and synthesized. Ten new compounds were synthesized and after proving their chemical structures were tested for antimicrobial activity using disk diffusion and microdilution method against Gram-negative bacterial strains (Escherichia coli and Pseudomonas aeruginosa), Gram-positive bacterial strains (Staphylococcus aureus and Enterococcus faecalis) and fungal strains (Candida albicans and Candida parapsilosis). Anti-biofilm activity and ethidium bromide accumulation assay results were also determined for the selected compounds. Among the tested compounds, hybrid compound H5 showed promising activity against E. faecalis with 16-fold potency compared to its precursor, TP5. Additionally, it has statistically significant inhibition of biofilm production at 10 μg/ml dose against E. coli and P. aeruginosa and a decreasing effect on the relative accumulation of ethidium bromide in P. aeruginosa at 100 μg/ml dose (85.07%) after 30 min. 2,5-disubstitued[1,2,4]triazolo[1,5-a]pyrimidinone heterocyclic core structure and its antimicrobial activity are reported to the literature for the first time in this study.
https://jrespharm.com/abstract.php?id=1012
Antimicrobial resistancetriazolopyrimidinoneN-(methylnaphthalene)piperazinemicrowave-assisted synthesisethidium bromide accumulationanti-biofilm activity