MULTI-TARGETED EFFECTS OF NOVEL MELATONIN ANALOGUES: AROMATASE INHIBITION, ER ANTAGONISM AND CYP1 INHIBITORY ACTIVITY YENİ MELATONİN ANALOGLARININ ÇOKLU HEDEFLİ ETKİLERİ: AROMATAZ İNHİBİSYONU, ER ANTAGONİZMASI VE CYP1 İNHİBİTÖR AKTİVİTESİ
Ankara Universitesi Eczacilik Fakultesi Dergisi, cilt.50, sa.3, ss.705-716, 2026 (Scopus, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 50 Sayı: 3
- Basım Tarihi: 2026
- Doi Numarası: 10.33483/jfpau.1770524
- Dergi Adı: Ankara Universitesi Eczacilik Fakultesi Dergisi
- Derginin Tarandığı İndeksler: Scopus, Central & Eastern European Academic Source (CEEAS), TR DİZİN (ULAKBİM)
- Sayfa Sayıları: ss.705-716
- Anahtar Kelimeler: Aromatase inhibition, breast cancer, CYP1 inhibition, estrogen receptor antagonism, melatonin analogues
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Ankara Üniversitesi Adresli: Evet
Özet
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.