2. Academic Validation
  3. Nonpungent N-AVAM Capsaicin Analogues and Cancer Therapy

Nonpungent N-AVAM Capsaicin Analogues and Cancer Therapy

  • J Med Chem. 2021 Feb 11;64(3):1346-1361. doi: 10.1021/acs.jmedchem.0c01679.
Stephen D Richbart 1,  Jamie R Friedman 2,  Kathleen C Brown 1,  Rama S Gadepalli 3,  Sarah L Miles 1,  John M Rimoldi 3,  Gary O Rankin 1,  Monica A Valentovic 1,  Maria T Tirona 4,  Paul T Finch 5,  Joshua A Hess 5,  Piyali Dasgupta 1
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, Toxicology Research Cluster, Joan C. Edwards School of Medicine, Marshall University, 1700 Third Avenue, Huntington, West Virginia 25755, United States.
  • 2 BioAgilytix Inc., 2300 Englert Drive, Durham, North Carolina 27713, United States.
  • 3 Department of Biomolecular Sciences, School of Pharmacy, Thad Cochran Research Center, University of Mississippi, University Avenue, University, Mississippi 38677, United States.
  • 4 Department of Hematology-Oncology, Edwards Cancer Center, Joan C. Edwards School of Medicine, Marshall University, 1400 Hal Greer Boulevard, Huntington, West Virginia 25755, United States.
  • 5 Department of Oncology, Edwards Cancer Center, Joan C. Edwards School of Medicine, Marshall University, 1400 Hal Greer Boulevard, Huntington, West Virginia 25755, United States.
PMID: 33508189 DOI: 10.1021/acs.jmedchem.0c01679
Abstract

Capsaicin displays robust growth-inhibitory activity in multiple human cancers. However, the feasibility of capsaicin as a clinically relevant Anticancer drug is hampered by its adverse side effects. This concern has led to extensive research focused on the isolation and synthesis of second-generation nonpungent capsaicin analogues with potent antineoplastic activity. A major class of nonpungent capsaicin-like compounds belongs to the N-acyl-vanillylamide (N-AVAM) derivatives of capsaicin (hereafter referred as N-AVAM capsaicin analogues). This perspective discusses the isolation of N-AVAM capsaicin analogues from natural sources as well as their synthesis by chemical and enzymatic methods. The perspective describes the pharmacokinetic properties and Anticancer activity of N-AVAM capsaicin analogues. The signaling pathways underlying the growth-inhibitory effects of N-AVAM capsaicin analogues have also been highlighted. It is hoped that the insights obtained in this perspective will facilitate the synthesis of a second generation of N-AVAM capsaicin analogues with improved stability and growth-suppressive activity in human Cancer.

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