TY - JOUR
T1 - Design, Synthesis, and Molecular Modeling Studies of a Novel Benzimidazole as an Aromatase Inhibitor
AU - Çevik, Ulviye Acar
AU - Celik, Ismail
AU - Mella, Jaime
AU - Mellado, Marco
AU - Özkay, Yusuf
AU - Kaplanclkll, Zafer Aslm
N1 - Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022
Y1 - 2022
N2 - In this study, a series of novel 1,3,4-oxadiazole-benzimidazole derivatives were designed and synthesized. Their cytotoxic activities against five cancer cell lines, including A549, MCF-7, C6, HepG2, and HeLa, were evaluated by the MTT assay. The compounds 5b,c showed satisfactory potencies with much higher anticancer activity in comparison to the reference drug doxorubicin against the studied cancer cell lines. In vitro, enzymatic inhibition assays of aromatase (ARO) enzymes were performed. Molecular docking, molecular dynamics simulations, and binding free energy analyses were used to better understand the structure-activity connections and mechanism of action of the aromatase inhibitors. Two types of satisfactory 3D-QSAR (CoMFA and CoMSIA) models were generated, to predict the inhibitory activities of the novel inhibitors. Molecular docking studies were also carried out to find their binding sites and types of their interactions with the aromatase enzyme. Additionally, molecular dynamics simulations were performed to explore the most likely binding modes of compounds 5b,c with CYP19A1.
AB - In this study, a series of novel 1,3,4-oxadiazole-benzimidazole derivatives were designed and synthesized. Their cytotoxic activities against five cancer cell lines, including A549, MCF-7, C6, HepG2, and HeLa, were evaluated by the MTT assay. The compounds 5b,c showed satisfactory potencies with much higher anticancer activity in comparison to the reference drug doxorubicin against the studied cancer cell lines. In vitro, enzymatic inhibition assays of aromatase (ARO) enzymes were performed. Molecular docking, molecular dynamics simulations, and binding free energy analyses were used to better understand the structure-activity connections and mechanism of action of the aromatase inhibitors. Two types of satisfactory 3D-QSAR (CoMFA and CoMSIA) models were generated, to predict the inhibitory activities of the novel inhibitors. Molecular docking studies were also carried out to find their binding sites and types of their interactions with the aromatase enzyme. Additionally, molecular dynamics simulations were performed to explore the most likely binding modes of compounds 5b,c with CYP19A1.
UR - http://www.scopus.com/inward/record.url?scp=85130410744&partnerID=8YFLogxK
U2 - 10.1021/acsomega.2c01497
DO - 10.1021/acsomega.2c01497
M3 - Article
AN - SCOPUS:85130410744
SN - 2470-1343
JO - ACS Omega
JF - ACS Omega
ER -