Synthesis and study of benzothiazole conjugates in the control of cell proliferation by modulating Ras/MEK/ERK-dependent pathway in MCF-7 cells
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- 作者：Ahmed Kamal ; Shaikh Faazil ; M. Janaki Ramaiah ; Md. Ashraf ; M. Balakrishna ; S.N.C.V.L. Pushpavalli ; Nibedita Patel ; Manika Pal-Bhadra
- 关键词：Ras/MEK/ERK ; Cell cycle ; Caspase-9 ; Benzothiazole&ndash ; pyrrole hybrid
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：15 October, 2013
- 年：2013
- 卷：23
- 期：20
- 页码：5733-5739
- 全文大小：1463 K
文摘
By applying a methodology, a series of benzothiazole-pyrrole based conjugates (4a-r) were synthesized and evaluated for their antiproliferative activity. Compounds such as 4a, 4c, 4e, 4g-j, 4m, 4n, 4o and 4r exhibited significant cytotoxic effect in the MCF-7 cell line. Cell cycle effects were examined for these conjugates at 2 ¦ÌM as well as 4 ¦ÌM concentrations and FACS analysis show an increase of G2/M phase cells with concomitant decrease of G1 phase cells thereby indicating G2/M cell cycle arrest by them. Interestingly 4o and 4r are effective in causing apoptosis in MCF-7 cells. Moreover, 4o showed down regulation of oncogenic expression of Ras and its downstream effector molecules such as MEK1, ERK1/2, p38 MAPK and VEGF. The apoptotic aspect of this conjugate is further evidenced by increased expression of caspase-9 in MCF-7 cells. Hence these small molecules have the potential to control both the cell proliferation as well as the invasion process in the highly malignant breast cancers.