¹Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ege University, 35040 Izmir, Türkiye
²Republic of Türkiye, Ministry of Agriculture and Forestry, Izmir Food Control Laboratory Directorate, Izmir, Türkiye
³Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan-06100, Ankara, Türkiye DOI : 10.29228/jrp.373 Melatonin (MLT) is a hormone that is secreted from pineal gland and regulates the circadian rhythm. It is reported to have anticancer effects in hormone dependent breast cancer via endocrine modulation, namely by antagonising the estrogen receptor (ER) or by inhibiting aromatase enzyme. However, its use is restricted because of its short half-life and poor bioavailability. Therefore, indole derived MLT analogues were synthesized previously, and they were shown to have potential antioxidant and anticancer effects. The present research is aimed to investigate the potential of MLT and its two newly synthesized analogues (M6 and M20) on steroidogenesis pathway by using an OECD validated in vitro method, H295R steroidogenesis assay (TG-456 test guideline). The compounds were incubated with H295R, human adenocarcinoma cells, for 48 hours and the hormone levels (testosterone; T and estradiol; E2) were detected by LC-MS/MS. The partial validation of the method was performed by using reference compounds forskolin, prochloraz, letrozole and ketoconazole. MLT decreased both E2 and T levels and its effect on E2 levels were dose dependent. On the other hand, M6 and M20 showed biphasic effects on both hormone levels. None of the compounds decreased H295R cell viability. These results demonstrate that depending on the use and the dose of these melatonin analogues, their potential effects on hormone production can result either in a therapeutical effect (such as anticancer agent) or a non-targeted endocrine related adverse effect when used as a pharmaceutical. Keywords : Steroidogenesis; melatonin analogues; therapeutical effect; endocrine related adverse effect; LC-MS/MS