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.
Keywords: caspase-3; gyrase binding mode; indole derivatives; liver fibrosis; phthalimide analogs; thalidomide.
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