New (3-(1H-benzo[d]imidazol-2-yl))/(3-(3H-imidazo[4,5-b]pyridin-2-yl))-(1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization inhibitorsElectronic supplementary information (ESI) available. See DOI: 10.1039/c7md00450h

• Main Authors: Mullagiri, Kishore, Nayak, V. Lakshma, Sunkari, Satish, Mani, Geeta Sai, Guggilapu, Sravanthi Devi, Nagaraju, Burri, Alarifi, Abdullah, Kamal, Ahmed
• Format: Journal Article
• Published: 21-02-2018
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c7md00450h

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.