Design, synthesis, biological evaluations, molecular docking, and in vivo studies of novel phthalimide analogs

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53–67% of erythromycin activity on the tested bacteria and 60–70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF‐7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad‐spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11, which showed good activity toward all the tested cell lines except for MCF‐7. The ability of the promising analogs 5, 8, and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase‐3 activation and Bcl‐2 assay of the best active derivatives 8, 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality. New phthalimide analogs with an indole or brominated indole moiety were synthesized and evaluated for their antimicrobial activity and their in vitro anticancer activity on HepG2, MCF‐7, A549, H1299, and Caco2 cells. The most promising analogs 5, 8, and 11 were tested for binding to topoisomerase II DNA gyrase. Histopathological studies in an in vivo model revealed that treatment with compound 8 improved fibrotic liver tissues to normality.