Design,synthesis, biological evaluations,molecular docking,and in vivo studies of novel phthalimide analogs |
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| Authors: | Magdy A. H. Zahran Bishoy El‐Aarag Ahmed B. M. Mehany Amany Belal Ali S. Younes |
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| Affiliation: | 1. Faculty of Science, Department of Chemistry, Menoufia University, Shebin El‐Koom, Egypt;2. Biochemistry Division, Faculty of Science, Department of Chemistry, Menoufia University, Shebin El‐Koom, Egypt;3. Faculty of Science, Department of Zoology, Al‐Azhar University, Cairo, Egypt;4. Faculty of Pharmacy, Department of Medicinal Chemistry, Beni‐Suef University, Beni‐Suef, Egypt |
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| Abstract: | 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. |
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| Keywords: | caspase‐3 gyrase binding mode indole derivatives liver fibrosis phthalimide analogs thalidomide |
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