Synthesis of a stable and orally bioavailable englerin analogue

  • Bioorg Med Chem Lett. 2016 Jun 1;26(11):2641-4. doi: 10.1016/j.bmcl.2016.04.016.
David M Fash  1 ,  Cody J Peer  2 ,  Zhenwu Li  1 ,  Ian J Talisman  1 ,  Sima Hayavi  3 ,  Florian J Sulzmaier  4 ,  Joe W Ramos  4 ,  Carole Sourbier  5 ,  Leonard Neckers  5 ,  W Douglas Figg  2 ,  John A Beutler  6 ,  William J Chain  7
Affiliations
  • 1. Department of Chemistry, University of Hawaii at Manoa, 2545 McCarthy Mall, Honolulu, HI 96822, United States.
  • 2. Genitourinary Malignancies Branch, National Cancer Institute, Frederick, MD 21702, United States.
  • 3. Developmental Therapeutics Program, National Cancer Institute, Frederick, MD 21702, United States.
  • 4. The University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, United States.
  • 5. Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, United States.
  • 6. Molecular Targets Laboratory, National Cancer Institute, Frederick, MD 21702, United States. Electronic address: [email protected].
  • 7. Department of Chemistry, University of Hawaii at Manoa, 2545 McCarthy Mall, Honolulu, HI 96822, United States; The University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, United States. Electronic address: [email protected].
PMID: 27107948 DOI: 10.1016/j.bmcl.2016.04.016
Abstract

Synthesis of analogues of englerin A with a reduced propensity for hydrolysis of the glycolate moiety led to a compound which possessed the renal Cancer cell selectivity of the parent and was orally bioavailable in mice.

Keywords
Bioavailability; Cancer; Englerins; Sesquiterpenes.