Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents

The current study was directed toward developing a new series of fused heterocycles incorporating indazolylthiazole moiety. The newly synthesized compounds were characterized through elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR, and Mass Spectrometry). The cytotoxic effect of the newly synthesized compounds was evaluated against normal human cells (HFB-4) and cancer cell lines (HepG-2 and Caco-2). Among the synthesized compounds, derivatives 4 , and 6 revealed a significant selective antitumor activity, in a dose-dependent manner, against both HepG-2 and Caco-2 cell lines, with lower risk toward HFB-4 cells (normal cells). Derivative 8 revealed the maximum antitumor activity toward both tumor cell lines, with an SI value of about 26 and IC50 value of about 5.9 μg/mL. The effect of these derivatives ( 8 , 4 , and 6 ) upon the expression of 5 tumor regulating genes was studied through quantitative real-time PCR, where its interaction with these genes was simulated through the molecular docking study. Furthermore, the antimicrobial activity results revealed that compounds 2 , 7 , 8 , and 9 have a potential antimicrobial activity, with maximum broad-spectrum activity through compound 3 against the three tested pathogens: Streptococcus mutans , Pseudomonas aeruginosa , and Candida albicans . The newly prepared compounds also revealed anti-biofilm formation activity with maximum activity against Streptococcus mutans , Pseudomonas aeruginosa , and Candida albicans , respectively.