ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis, in silico molecular modeling and in vitro pharmacological evaluations of biphenyl-4-carboxamide derivatives

Muhammad Salman Javed, Muhammad Zubair, Komal Rizwan, Muhammad Jamil, and Ataf Ali Altaf

Department of Chemistry, Government College University Faisalabad, Faisalabad, Pakistan

E-mail: zubairmkn@gcuf.edu.pk

Received: 15 February 2023  Accepted: 1 May 2024

Abstract:

We have synthesized library of biphenyl-4-carboxamide derivatives via one-pot strategy. The synthesized molecules were pharmacologically tested for their anticancer, antimicrobial activities and inhibition potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and urease enzymes. Molecular docking studies were performed against AChE, BChE and urease to further investigate the inhibition mechanism of the synthesized compounds. Compound 4h (at conc. 100 μg/mL) was found to be most active against human liver cancer cell lines (Hep2) (cell viability = 29.33%). Compound 4c demonstrated potent inhibitory activity against AChE (% inhibition 84.36) at 0.5 mM concentration and urease (% inhibition 31.42) enzymes at 0.25 mM concentration while 4b showed good activity against BChE (% inhibition 52.19) at 0.5 mM concentration. Synthesized molecules showed potent antibacterial and antifungal activities. To rationalize the observed pharmacological activities, we performed docking studies against AChE, BChE and enzymes. Compounds 4f, 4b and 4h showed high binding affinity with AChE, BChE and urease, respectively, with lowest bonding energies values (− 12.4, − 11.5 and − 8.9), respectively, so molecular docking study showed that all the synthesized compounds have good binding capability targeted to AChE, BChE and urease enzymes. Pharmaceutical activities and molecular docking studies suggest that synthesized compounds may play a great role as pharmaceutical agents.

Keywords: Biphenyl-4-carboxamide; Thiourea; Anticancer; BChE; AChE; Urease; Docking

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-024-03497-0

Chemical Papers 78 (10) 5865–5877 (2024)