New (3-(1-benzo[]imidazol-2-yl))/(3-(3-imidazo[4,5-]pyridin-2-yl))-(1-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization inhibitors

A series of new (3-(1 H -benzo[ d ]imidazol-2-yl))/(3-(3 H -imidazo[4,5- b ]pyridin-2-yl))-(1 H -indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates 4-6(a-i) were synthesized and evaluated for their antiproliferative activity on selected human cancer cell lines such as prostate (DU-145), lung (A...

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Bibliographic Details
Published in:MedChemComm 2018-02, Vol.9 (2), p.275-281
Main Authors: Mullagiri, Kishore, Nayak, V. Lakshma, Sunkari, Satish, Mani, Geeta Sai, Guggilapu, Sravanthi Devi, Nagaraju, Burri, Alarifi, Abdullah, Kamal, Ahmed
Format: Article
Language:English
Subjects:
Annexin V
Apoptosis
Cancer
Cervix
Conjugates
Cytotoxicity
Immunofluorescence
Lungs
Membrane potential
Mitochondria
Polymerization
Prostate
Prostate cancer
Toxicity
Tubulin
Tumor cell lines
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Summary:A series of new (3-(1 H -benzo[ d ]imidazol-2-yl))/(3-(3 H -imidazo[4,5- b ]pyridin-2-yl))-(1 H -indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates 4-6(a-i) were synthesized and evaluated for their antiproliferative activity on selected human cancer cell lines such as prostate (DU-145), lung (A549), cervical (HeLa) and breast (MCF-7). Most of these conjugates showed considerable cytotoxicity with IC 50 values ranging from 0.54 to 31.86 μM. Among them, compounds 5g and 6f showed significant activity against human prostate cancer cell line DU-145 with IC 50 values of 0.68 μM and 0.54 μM, respectively. Tubulin polymerization assay and immunofluorescence analysis results suggest that these compounds effectively inhibit microtubule assembly formation in DU-145. Further, the apoptosis-inducing ability of these derivatives ( 5g and 6f ) was confirmed by Hoechst staining, measurement of mitochondrial membrane potential and ROS generation and annexin V-FITC assays. A series of new benzimidazole-indole linked phenstatin conjugates 4-6(a-i) were synthesized and evaluated for their anticancer activity.
ISSN:2040-2503
2040-2511
DOI:10.1039/c7md00450h