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.
Keywords: Antidiarrheal; Cytotoxic; Heteroarylamides; Peripheral analgesic; Synthesis.
© 2024 The Authors.