Design, synthesis, anticancer evaluation, molecular docking, and in silico ADME analysis of novel chalcones incorporated indole-pyrimidine derivatives as promising anticancer agents

Abstract

A novel library of aryl rings attached chalcone derivatives of indole-pyrimidines ( 10a-j ) were designed, synthesized, and evaluated for anticancer activities against four human cancer cell lines such as PC3, DU-145 (prostate), A549 (lung), and (MCF-7 (breast) by employing MTT method. The results of the MTT assay showed that all the synthetic compounds had some tumor cell growth inhibitory activities with IC 50 values range from 0.01±0.005 µM to 14.6 ± 6.32 µM, and standard drug with values 1.97 ± 0.45 µM to 3.08 ± 0.135 µM, respectively. Among them, compounds ( 10a, 10b, 10c, 10d , and 10e ) displayed remarkable activities, and out of which compounds 10a and 10d were found to be the most promising with potential anti-cancer activity. Molecular docking studies of the compounds were carried out against SARM (PDB ID: 3V49) and the docking results exclusively proposed binding modes in the active site of SARM. Among all, 10a, 10b, 10d , 10 h and 10j showed comparable dock score, 10a and 10b (-142.89 and -145.13) displayed pronounced interactions when compared with co-crystal ligand (-143.40) . Finally, in silico predictions of ADME and pharmacokinetic parameters indicated that all these compounds could be considered as drug candidates with oral bioavailability.