Furan-2-carboxamide derivative, a novel microtubule stabilizing agent induces mitotic arrest and potentiates apoptosis in cancer cells

• Published in: Bioorganic chemistry Vol. 108; p. 104586
• Main Authors: Shwetha, B, Sudhanva, M. Srinivasa, Jagadeesha, G.S, Thimmegowda, N.R, Hamse, Vivek K., Sridhar, B.T, Thimmaiah, K.N, Ananda Kumar, C.S, Shobith, Rangappa, Rangappa, K.S
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.03.2021; Elsevier
• Subjects: Anticancer agents; Apoptosis; Biochemistry & Molecular Biology; Chemistry; Chemistry, Organic; Furan-2-carboxamide; Life Sciences & Biomedicine; Microtubule stabilizing agents; Physical Sciences; Science & Technology; Furan-2-carboxamide; Anticancer agents; Microtubule stabilizing agents; Apoptosis
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104586

[Display omitted] •SH09, induces mitotic arrest and promotes apoptosis in various cancer cells.•SH09, decreases colony formation and mitigates invasion and migratory capabilities.•SH09, Stabilizes tubulins polymers and enhances polymerized form of tubulins.•Docking confirms efficient binding of SH09 to paclitaxel binding site of tubulin. The vital role played by microtubules in the cell division process, marks them as a potential druggable target to decimate cancer. A novel furan-2-carboxamide based small molecule, is a selective microtubule stabilizing agent (MSA) with IC50 ranging from 4 µM to 8 µM in different cancer cell lines. Inhibition of tubulin polymerization or stabilization of tubulin polymers abrogates chromosomal segregation during cell division, results in cell cycle arrest and leads to cell death due to the delayed repair mechanism. A novel furan-2-carboxamide based small molecule exhibited potent anti-proliferative and anti-metastatic property In-Vitro against the panel of cancer cells. Annexin V-FITC/PI, double staining reveals potent cytotoxic effect of SH09 against HeLa cells. FACS analysis displays induction of G2/M arrest and accumulation of subG1 population of cells upon treatment with SH09. Molecular docking study unveils SH09 binding affinity to the Taxol binding pocket of tubulin proteins and MM-GBSA also confirms strong binding energies of SH09 with tubulin proteins.