There is an urgent global need to develop new antimicrobial and anti-cancer drugs. In the current study, the biological evaluation of some synthesized phenylsulfonyl of benzothiazole and benzimidazole moiety-containing pyrazolo [5, 1-c]-l, 2, 4-triazine derivative [6, 7, 11.12, 16 and 17], arylhydrazone derivatives and pyridazine derivative [20, 21, 25, 26, 29 and 29] was carried out for antimicrobial and anticancer activity. The synthesized compounds containing pyrazolo [5, 1-c]-l, 2, 4-triazine derivative [6, 7] exhibited higher activity against Staphylococcus aureus compared with control drug Chloramphenicol. While arylhydrazones 20 and 21 were found to be equal to the control drug. For antifungal activity, the compounds 6, 7, 20 and 21 were possessed the same potency as cycloheximide against Aspergillus fumigatus. The anticancer activity on Hepatocellular carcinoma (HEPG2) of the compounds 6, 7, 20 and 21 exhibited excellent activities, more potent than the reference drug. The findings of this study are worthwhile; however, further pharmaceutical and toxicological studies are recommended to be carried out.