Synthesis of a stable and orally bioavailable englerin analogue

David M Fash; Cody J Peer; Zhenwu Li; Ian J Talisman; Sima Hayavi; Florian J Sulzmaier; Joe W Ramos; Carole Sourbier; Leonard Neckers; W Douglas Figg; John A Beutler; William J Chain

doi:10.1016/j.bmcl.2016.04.016

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. Epub 2016 Apr 8.

Authors

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].

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.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Administration, Oral
Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Biological Availability
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Mice
Molecular Structure
Rats
Sesquiterpenes, Guaiane / administration & dosage
Sesquiterpenes, Guaiane / chemistry
Sesquiterpenes, Guaiane / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Sesquiterpenes, Guaiane
englerin A

Abstract

Publication types

MeSH terms

Substances

Grants and funding