Imidazopyridine linked triazoles as tubulin inhibitors, effectively triggering apoptosis in lung cancer cell line

• Published in: Bioorganic chemistry Vol. 80; pp. 714 - 720
• Main Authors: Sayeed, Ibrahim Bin, Vishnuvardhan, M.V.P.S., Nagarajan, Apoorva, Kantevari, Srinivas, Kamal, Ahmed
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.10.2018; Elsevier
• Subjects: Apoptosis; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Imidazopyridine; Life Sciences & Biomedicine; Lung cancer; Physical Sciences; Science & Technology; Triazoles; Tubulin; Imidazopyridine; Tubulin; Triazoles; Lung cancer; Apoptosis; 1,2,3-TRIAZOLE; DEATH; MICROTUBULE DYNAMICS; DIVISION; MITOSIS; ARREST; POTENT; BIOLOGICAL EVALUATION; AGENTS
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2018.07.026

[Display omitted] •Imidazopyridine-triazole conjugates 8(a-r) were synthesized and evaluated for their anti-proliferative activity.•Conjugates 8 g and 8j showed IC50 values 0.51 & 0.63 µm respectively.•Conjugates arrest cell growth in G2/M phase indicating tubulin arrest.•Triggering of apoptosis was confirmed through Hoescht staining and annexin V assay. A library of new imidazopyridine linked triazole hybrid conjugates (8a-r) were designed, synthesized and evaluated for their cytotoxicity against four cancer cell lines namely, human lung (A549), human prostate (DU-145), human colon (HCT-116) and breast (MDA-MB 231) cancer. These conjugates exhibited good to moderate activity against the tested human cancer cell lines. Two of the conjugates (8g and 8j) showed significant antitumor activity against human lung cancer cell line (A549) with IC50 values of 0.51 µM and 0.63 µM respectively. Flow cytometry analysis revealed that these conjugates arrested the cell cycle at G2/M phase in human lung cancer cell line (A549). Immune-histochemistry and tubulin polymerization assay suggest inhibition of tubulin. Hoechst staining, annexin V and DNA fragmentation by tunnel assay suggested that these compounds induce cell death by apoptosis. Overall, the current study demonstrates that the synthesis of imidazopyridine linked triazole conjugates as promising anticancer agents causing G2/M arrest and apoptotic-inducing ability.