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

  • Bioorg Med Chem Lett. 2017 Sep 15;27(18):4314-4318. doi: 10.1016/j.bmcl.2017.08.033.
Srinivas Burra  1 ,  Vani Voora  2 ,  Ch Prasad Rao  1 ,  P Vijay Kumar  1 ,  Rama Krishna Kancha  2 ,  G L David Krupadanam  3
Affiliations
  • 1. Natural Products Lab, Dept. of Chemistry, Osmania University, Hyderabad 500007, India.
  • 2. Molecular Medicine and Therapeutics Laboratory, CPMB, Osmania University, Hyderabad 500007, India.
  • 3. Natural Products Lab, Dept. of Chemistry, Osmania University, Hyderabad 500007, India. Electronic address: [email protected].
PMID: 28838692 DOI: 10.1016/j.bmcl.2017.08.033
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.

Keywords
1,3-Dipolar cycloadditions; Breast cancer; Forskolin; Isoxazoles; Regioselectivity.