Heterocyclic compounds with different moieties: synthesis and evaluation of biological activities assisted with the computational study

Abstract

In the present work, heterocyclic compounds containing different moieties, such as pyrazole and thiophene, were synthesized and screened for inhibitory potency against medicinal enzymes and bacterial and cancer (breast and cervical) cell lines. The synthesized compounds have exhibited inhibitory capability against the studied enzymes. Among substances, C3 compound showed AChE and BChE inhibitory potency with the lowest IC50 value of 3.72 ± 0.57 and 1.66 ± 0.22 µM, respectively, in comparison to the standard tacrine. These analogs indicated varying degrees of tyrosinase inhibitory potencies ranging from 1.12 ± 0.50 to 7.70 ± 0.88 µM, and substance C4 was more potent against the enzyme than the reference compound, kojic acid. All four compounds have IC50 values between 37.11 ± 1.56–124.8 ± 2.09 µM for α-glucosidase. It was found that compound C1 exhibited a better antiproliferative activity compared to other substances, with IC50 values at 5.068 and 6.460 µg mL−1 for MCF-7 and HeLa cells, respectively. C1 and C2 compounds had good inhibitory ability against E. faecalis with a MIC value (16 µg mLˉˡ). Molecular docking analysis showed that C3 has the lowest binding score against α-glucosidase (-8.617 kcal/mol). Communicated by Ramaswamy H. Sarma