Work

Multi-targeted Effects of Novel Melatonin Analogues: Aromatase Inhibition, Er Antagonism and Cyp1 Inhibitory Activity

Year: 2026

Type: article

Abstract: Objective: This study aimed to synthesize and evaluate novel chlorophenyl-substituted melatonin analogues for their potential multi-target effects in hormone-dependent breast cancer. Their inhibitory activity on aromatase (CYP19A1), antagonistic potential on estrogen receptor (ER), inhibition of CYP1 enzymes, and selective cytotoxicity on cancer cells were investigated.Material and Method: Two groups of novel indole-based melatonin analogues (non-benzylated and benzylated) were synthesized and structurally characterized. Aromatase inhibition was assessed using a cell-free fluorescence-based assay. ER antagonism was evaluated in MCF-7 BUS cells using the E-Screen assay. CYP1 enzyme inhibition was determined via EROD assay using rat liver microsomes. Cytotoxicity was evaluated in MCF-7 BUS and MCF-10A cells using the MTT assay.Result and Discussion: Non-benzylated new compounds (2a–2f) showed higher aromatase and CYP1 inhibition compared to benzylated derivatives (4a–4e). Compound 2f exhibited the highest aromatase (78.5%) and CYP1 (79%) inhibition, and significant ER antagonism. New benzylated compounds displayed stronger cytotoxicity in MCF-7 BUS cells but less enzymatic inhibition. Compound 2f showed a favorable multi-target profile with selective cytotoxicity.

Source: Ankara Universitesi Eczacilik Fakultesi Dergisi

DOI: 10.33483/jfpau.1770524

Authors: Elif İnce Erguc, Hanif Şirinzade, Nil Bita Entezari Ökeer, Sibel Süzen, Hande Gürer-orhan

Institutions: Izmir Kâtip Çelebi University, Selçuk University, Ege University, Ankara University

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: Ege Üniversitesi, Türkiye Bilimsel ve Teknolojik Araştırma Kurumu