AUTHOR=Malik M. Shaheer , Alsantali Reem I. , Jamal Qazi Mohammad Sajid , Seddigi Zaki S. , Morad Moataz , Alsharif Meshari A. , Hussein Essam M. , Jassas Rabab S. , Al-Rooqi Munirah M. , Abduljaleel Zainularifeen , Babalgith Ahmed O. , Altass Hatem M. , Moussa Ziad , Ahmed Saleh A. 

TITLE=New Imidazole-Based N-Phenylbenzamide Derivatives as Potential Anticancer Agents: Key Computational Insights

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.808556

DOI=10.3389/fchem.2021.808556

ISSN=2296-2646

ABSTRACT=<p>An efficient atom-economical synthetic protocol to access new imidazole-based <italic>N</italic>-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of <italic>N-phenylbenzamide</italic> derivatives in a short reaction time (2–4 h) with an 80–85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC<sub>50</sub> values between 7.5 and 11.1 μM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents.</p>