Synthesis of novel forskolin isoxazole derivatives with potent anti-cancer activity against breast cancer cell lines.

Abstract

Forskolin C1-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 IC50≤1µM. The derivative 14f exhibited highest activity in both p53-positive (MCF-7) and p53-negative (BT-474) breast cancer cell lines with an IC50 of 0.5µM.

• Authors: Srinivas Burra, Vani Voora, Ch Prasad Rao, P Vijay Kumar, Rama Krishna Kancha, G L David Krupadanam
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 27 Issue 18 Pg. 4314-4318 (09 15 2017) ISSN: 1464-3405 [Electronic] England
• PMID: 28838692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017. Published by Elsevier Ltd.

Chemical References

• Antineoplastic Agents
• Isoxazoles
• Colforsin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colforsin (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Isoxazoles (chemical synthesis, chemistry, pharmacology)
• MCF-7 Cells
• Molecular Structure
• Structure-Activity Relationship