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ID: ALA5226292

Journal: J Med Chem

Title: Nonpungent N-AVAM Capsaicin Analogues and Cancer Therapy.

Authors: Richbart SD, Friedman JR, Brown KC, Gadepalli RS, Miles SL, Rimoldi JM, Rankin GO, Valentovic MA, Tirona MT, Finch PT, Hess JA, Dasgupta P.

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.

CiteXplore: 33508189

DOI: 10.1021/acs.jmedchem.0c01679