Synthesis and pharmacological evaluation of heteroarylamide derivatives as potential analgesic, anti-inflammatory, antidiarrheal and cytotoxic agents

Six heteroarylamide derivatives were synthesized in good yields and screened for several biological activities. Compounds 1–5 demonstrated analgesic activity with percentage inhibition of writhing between 77.10 and 95.79 %, comparable to that of the standard aceclofenac having 91.12 % writhing inhibition. Evaluation of anti-inflammatory activity unveiled that compound 4 exhibited 36.9 %, 64.17 %, 82.9 % and 93.9 % inhibition of paw edema as compared to aceclofenac's inhibition of 35.5 %, 78.6 %, 79.3 % and 91.2 % at the 1st, 2nd, 3rd and 4th hours, respectively. Compounds 5 and 6 exerted considerable antidiarrheal effects with 85.00 % and 71.67 % inhibition of defecation at 25 mg/kg dose, respectively, whereas, the standard loperamide showed 85.00 % inhibition. Compounds 4–6 manifested promising activity in brine shrimp lethality bioassay as well as in trypan blue dye exclusion assay, resulting in 10–20 % cell viability on HeLa cell line and compound 5 was found to have the lowest IC50 of 281.96 μM in the MTT assay. Molecular docking analysis suggested that certain macromolecular targets such as cyclooxygenase-2, muscarinic M3 receptor and matrix metalloproteinase 9 (MMP9) might be involved for the observed activities. As predicted by in silico ADME/T analysis, the compounds also possessed good pharmacokinetic properties. •Six heteroarylamide derivatives were synthesized in 68–85 % yields.•Some of the synthesized samples showed promising analgesic, anti-inflammatory and antidiarrheal activity.•MTT assay revealed moderate cytotoxic effects of several test samples.•Molecular docking analysis and in silico ADMET studies supplemented the above results.