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2‐Propyl‐3‐Aminoquinazoline‐4(3H)‐one Derivatives as Potential Androgen Receptor Inhibitors: Synthesis and Cytotoxicity Against PC3 Cell Line via In Vitro and In Silico Studies     
Yazarlar (7)
Halil Şenol
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye
Furkan Çakır
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye
Şeyma Ateşoğlu
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye
Pelin Tokalı
Ayşe Merve Şenol
Sağlık Bilimleri Üniversitesi, Türkiye
Fahri Akbaş
Bezm-İ Âlem Vakıf Üniversitesi, Türkiye
Doç. Dr. Feyzi Sinan TOKALI Doç. Dr. Feyzi Sinan TOKALI
Kafkas Üniversitesi, Türkiye
Devamını Göster
Özet
Twenty-one novel quinazolin-4(3H)-one derivatives were synthesized and evaluated for their cytotoxic effects against the PC3 prostate cancer cell line. Structural characterization was performed using FTIR, NMR, and HRMS spectroscopy. Cytotoxicity assays revealed that compound 1 exhibited the highest potency (IC = 4.29 ± 0.32 µM) and selectivity (SI = 20.1) against PC3 cells, surpassing the reference drug sorafenib. Compounds 10 and 11 also demonstrated significant selectivity (SI = 12.7 and 12.4, respectively), making them promising candidates for further investigation. Molecular docking studies confirmed strong binding affinities to the androgen receptor (AR), with compound 1 displaying the most favorable interaction (IFD Glide Score = -15.137 kcal/mol, MM-GBSA = -72.11 kcal/mol). MD simulations further supported the stability of compound 1 within the receptor binding site, highlighting key hydrogen bonding and π-π stacking interactions. ADME predictions indicated favorable pharmacokinetic properties, with all active compounds complying with drug-likeness criteria and exhibiting high oral absorption. Overall, these findings suggest that quinazolinone derivatives, particularly compound 1, hold significant potential as selective anticancer agents targeting prostate cancer.
Anahtar Kelimeler
ADME | androgen receptor | molecular docking | prostate cancer | quinazolin-4(3H)-one
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Archiv der Pharmazie
Dergi ISSN 0365-6233 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q2
Makale Dili İngilizce
Basım Tarihi 07-2025
Cilt No 358
Sayı 7
Doi Numarası 10.1002/ardp.70048
Makale Linki https://doi.org/10.1002/ardp.70048