Design and synthesis of 4-morpholino-6-(1, 2, 3, 6-tetrahydropyridin-4-yl)-N-(3, 4, 5-trimethoxyphenyl)-1, 3, 5-triazin-2-amine analogues as tubulin polymerization inhibitors. Issue 16 (15th August 2017)

• Record Type: Journal Article
• Authors: Narva, Suresh; Chitti, Surendar; Amaroju, Suresh; Bhattacharjee, Debanjan; Rao, Bala Bhaskara; Jain, Nishant; Alvala, Mallika; Sekhar, Kondapalli Venkata Gowri Chandra
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 16(2017)
• Page Start: 3794
• Page End: 3801
• Publication Date: 2017-08-15
• Subjects: 1, 3, 5-Triazine -- Morpholine -- Antiproliferative activity -- Tubulin polymerization -- Molecular docking study; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.06.060
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: New 1, 3, 5-triazine analogues were synthesized and evaluated for anticancer activity. Cytotoxic evaluation carried against HeLa, HepG2, A549 and MCF-7 cell lines. 8j showed strong inhibitory effect (IC50 = 9.6 μM) against HepG2 cell line. 8j was found to arrest the cells in the G2/M phase and disrupt the microtubule. 8j binds to nocodazole binding site of tubulin with a binding affinity of −7.949. Abstract: A series of thirty-seven 1, 3, 5-triazine analogues have been synthesized, characterized and evaluated for their antiproliferative activity against a panel of four different human cancer cell lines such as HeLa, HepG2, A549 and MCF-7. Most of the 1, 3, 5-triazine analogues exhibited promising antiproliferative activity against tested cancer cell lines. Among all the synthesized compounds, 8j showed potent activity against the cancer cell lines such as HeLa, HepG2, A549 and MCF-7 with IC50 12.3 ± 0.8, 9.6 ± 0.4, 10.5 ± 1.0 and 11.7 ± 0.5 μM respectively.8j was taken up for elaborate biological studies and the cells in the cell cycle were arrested in G2/M phase. In addition, 8j was examined for its effect on the microtubule system with a tubulin polymerization assay, immunofluorescence.8j showed remarkable inhibition of tubulin polymerization. Molecular docking studies were also carried out to understand the binding pattern. The studies suggested that8j has a good binding affinity of −7.949 towards nocodazole binding site of tubulin while nocodazole has −7.462.