TY - JOUR
T1 - New Imidazole-Based N-Phenylbenzamide Derivatives as Potential Anticancer Agents
T2 - Key Computational Insights
AU - Malik, M. Shaheer
AU - Alsantali, Reem I.
AU - Jamal, Qazi Mohammad Sajid
AU - Seddigi, Zaki S.
AU - Morad, Moataz
AU - Alsharif, Meshari A.
AU - Hussein, Essam M.
AU - Jassas, Rabab S.
AU - Al-Rooqi, Munirah M.
AU - Abduljaleel, Zainularifeen
AU - Babalgith, Ahmed O.
AU - Altass, Hatem M.
AU - Moussa, Ziad
AU - Ahmed, Saleh A.
N1 - Funding Information:
The authors would like to acknowledge the Deanship of Scientific Research at Umm Al-Qura University, for supporting this work by Grant code: 22UQU4320545DSR01. The authors would like to extend their sincere appreciation to Taif University researchers for supporting the project (number TURSP-2020/312), Taif University, Taif, Saudi Arabia. ZM is grateful to the United Arab Emirates University (UAEU) of Al-Ain and to the Research Office for supporting the research developed in his laboratory (Grant no. G00003291).
Publisher Copyright:
Copyright © 2022 Malik, Alsantali, Jamal, Seddigi, Morad, Alsharif, Hussein, Jassas, Al-Rooqi, Abduljaleel, Babalgith, Altass, Moussa and Ahmed.
PY - 2022/1/19
Y1 - 2022/1/19
N2 - An efficient atom-economical synthetic protocol to access new imidazole-based N-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide 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 IC50 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.
AB - An efficient atom-economical synthetic protocol to access new imidazole-based N-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide 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 IC50 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.
KW - ADME and drug-likeness
KW - N-phenylbenzamide
KW - anticancer activity
KW - computational studies
KW - imidazole
KW - molecular dynamic simulations
KW - multicomponent reaction
UR - http://www.scopus.com/inward/record.url?scp=85124520284&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85124520284&partnerID=8YFLogxK
U2 - 10.3389/fchem.2021.808556
DO - 10.3389/fchem.2021.808556
M3 - Article
AN - SCOPUS:85124520284
SN - 2296-2646
VL - 9
JO - Frontiers in Chemistry
JF - Frontiers in Chemistry
M1 - 808556
ER -