Department of Biomedical Sciences, Toxicology Research Cluster, Joan C. Edwards School of Medicine, Marshall University, 1700 Third Avenue, Huntington, West Virginia 25755, United States.
BioAgilytix Inc., 2300 Englert Drive, Durham, North Carolina 27713, United States.
J Med Chem. 2021 Feb 11;64(3):1346-1361. doi: 10.1021/acs.jmedchem.0c01679. Epub 2021 Jan 28.
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 -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.
辣椒素在多种人类癌症中表现出强大的生长抑制活性。然而，由于其不良反应，辣椒素作为一种临床相关的抗癌药物的可行性受到阻碍。这一担忧促使人们进行了广泛的研究，专注于分离和合成具有强大抗肿瘤活性的第二代非刺激性辣椒素类似物。一类主要的非刺激性辣椒素类化合物属于辣椒素的 -酰基-香草基酰胺（N-AVAM）衍生物（以下简称 N-AVAM 辣椒素类似物）。本观点讨论了从天然来源中分离 N-AVAM 辣椒素类似物以及通过化学和酶法合成它们的方法。本观点描述了 N-AVAM 辣椒素类似物的药代动力学特性和抗癌活性。还强调了 N-AVAM 辣椒素类似物的生长抑制作用的信号通路。希望本观点中获得的见解将有助于合成第二代 N-AVAM 辣椒素类似物，提高其在人类癌症中的稳定性和生长抑制活性。
