Investigation of novel imidazo[1,2-a]pyrazine derivatives as antiproliferative agents and their enzymatic inhibition effect against MMP-9

Ten N-(2/3/4-substituted phenyl)-2-(imidazo[1,2-a]pyrazin-2-carbonyl)hydrazin-1-carbothioamide derivatives (2a–2j) were synthesized, analyzed utilizing ¹H-NMR,¹³C-NMR, and HRMS. Their antiproliferative activity against the cancerous A549 cell line, and the healthy L929 cell line as well as their potential enzymatic inhibition effect against matrix metalloproteinase-9 (MMP-9) were evaluated. In terms of cytotoxicity, none of the compounds show similar activity against the A549 cell line compared to the reference cisplatin, however, derivatives 2h and 2i that contain 2-chlorophenyl and 3-chlorophenyl moieties, respectively had the highest potency compared to other derivatives, while none of the compounds were cytotoxic against the normal L929 cell line. In terms of MMP-9 inhibition activity, compounds 2f and 2g were the most potent inhibitors compared to other derivatives with % inhibitions of 46.54 and 26.81, respectively. The binding of compound 2f with the ion Zn301 and its bonding amino acids His 230 and His 226 are noticed to be the characteristic interactions that significantly affect the inhibition of MMP-9 enzyme according to the docking studies.