Burra Srinivas, Voora Vani, Rao Ch Prasad, Vijay Kumar P, Kancha Rama Krishna, David Krupadanam G L
Natural Products Lab, Dept. of Chemistry, Osmania University, Hyderabad 500007, India.
Molecular Medicine and Therapeutics Laboratory, CPMB, Osmania University, Hyderabad 500007, India.
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4314-4318. doi: 10.1016/j.bmcl.2017.08.033. Epub 2017 Aug 16.
Forskolin C-isoxazole derivatives (3,5-regioisomers) (11a-e, 14, 15a-h and 15, 16a-g) were synthesized regioselectively by adopting 1,3-dipolar cycloadditions. These derivatives were tested using estrogen receptor positive breast cancer cell lines MCF-7 and BT-474. Majority of the compounds exhibited activity against the p53-positive MCF-7 breast cancer cells but not against the p53-negative BT-474 breast cancer cells. Among forskolin derivatives, compounds 11a, 11c, 14a, 14f, 14g, 14h, 15b, 16g and 17b exhibited higher anti-cancer activity against MCF-7 cell line with an IC≤1µM. The derivative 14f exhibited highest activity in both p53-positive (MCF-7) and p53-negative (BT-474) breast cancer cell lines with an IC of 0.5µM.
通过1,3 - 偶极环加成反应区域选择性地合成了福斯高林C - 异恶唑衍生物（3,5 - 区域异构体）（11a - e、14、15a - h和15、16a - g）。使用雌激素受体阳性乳腺癌细胞系MCF - 7和BT - 474对这些衍生物进行了测试。大多数化合物对p53阳性的MCF - 7乳腺癌细胞有活性，但对p53阴性的BT - 474乳腺癌细胞无活性。在福斯高林衍生物中，化合物11a、11c、14a、14f、14g、14h、15b、16g和17b对MCF - 7细胞系表现出更高的抗癌活性，IC≤1µM。衍生物14f在p53阳性（MCF - 7）和p53阴性（BT - 474）乳腺癌细胞系中均表现出最高活性，IC为0.5µM。
