Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Marmara Pharmaceutical Journal 2015 , Vol 19 , Issue 2
Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents
Esra TATAR1, Sukriye Guniz KUCUKGUZEL1, Sevgi KARAKUS1, Eric De CLERCQ2, Graciela ANDREI2, Robert SNOECK2, Christophe PANNECOUQUE2, Sinem OKTEM-OKULLU3, Nihal UNUBOL3, Tanıl KOCAGOZ3, Sadık KALAYCI4, Fikrettin SAHIN4, İlkay KUCUKGUZEL1
1Marmara University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Haydarpaşa 34668 İstanbul, Turkey
2Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
3Acıbadem University, School of Medicine, Department of Medical Microbiology, Maltepe 34848 İstanbul, Turkey
4Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 İstanbul, Turkey DOI : 10.12991/mpj.2015199639 Some novel 1,3,4-thiadiazole [5-8] and 1,2,4-triazole [9-12] derivatives carrying amino acid moiety were synthesized starting from L-methionine. 1,3,4-Thiadiazole and 1,2,4-triazole scaffolds were prepared by cyclocondensation of the corresponding thiosemicarbazide and finally converted to their thiourea derivatives. Structures of the synthesized compounds [4-12] were confirmed by IR, 1H-NMR and 13C-NMR spectral data and elemental analysis. Synthesized compounds were evaluated for their antiviral and antibacterial activity. Of the screened compounds, N-{3-(methylsulfanyl)- 1-[5-(phenylamino)-1,3,4-thiadiazole-2-yl]propyl}benzamide [5] was identified as the most potent inhibitor of Influenza A H3N2 virus with an EC50 value of 31.4 μM, which serves as a lead compound for prospective development. The antituberculosis activity screen of the synthesized compounds revealed

1-[4-(4-chloro-(3-trifluoromethyl)phenyl]-3-[3-(methylsulfanyl)- 1-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazole- 3-yl)propyl]thiourea [12] as the most active compound against M. tuberculosis H37Rv strain (MIC : 30.88 μM) but the compound proved not selective. Keywords : Thioureas; 1,3,4-thiadiazoles; 1,2,4-triazoles; antiviral activity; influenza; antituberculosis activity

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