Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxypheny l)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors

作者：Narva Suresh; Chitti Surendar; Amaroju Suresh; Bhattacharjee Debanjan; Rao Bala Bhaskara; Jain Nishant; Alvala Mallika; Sekhar Kondapalli Venkata Gowri Chandra^*

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(16): 3794-3801.

DOI：10.1016/j.bmcl.2017.06.060

• 1,3,5-Triazine
• Morpholine
• Antiproliferative activity
• Tubulin polymerization
• Molecular docking study

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 mu M 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 micro tubule 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 that 8j has a good binding affinity of -7.949 towards nocodazole binding site of tubulin while nocodazole has -7.462.

• 出版日期2017-8-15