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

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.

• Authors: Magdy A H Zahran, Bishoy El-Aarag, Ahmed B M Mehany, Amany Belal, Ali S Younes
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 351 Issue 5 Pg. e1700363 (May 2018) ISSN: 1521-4184 [Electronic] Germany
• PMID: 29611624 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2018 Deutsche Pharmazeutische Gesellschaft.

Chemical References

• Anti-Bacterial Agents
• Antifungal Agents
• Antineoplastic Agents
• Phthalimides

Topics

• A549 Cells
• Animals
• Anti-Bacterial Agents (chemical synthesis, chemistry, pharmacology)
• Antifungal Agents (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Caco-2 Cells
• Disease Models, Animal
• Hep G2 Cells
• Humans
• Liver Cirrhosis (drug therapy)
• MCF-7 Cells
• Male
• Mice
• Microbial Sensitivity Tests
• Molecular Docking Simulation
• Neoplasms (drug therapy, pathology)
• Phthalimides (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship