Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9‐Epipolygodial against Drug‐Resistant Cancer Cells
Year: 2015
Type: article
Abstract: Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1-agonist and anticancer activities. These experiments led to the identification of 9-epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9-Epipolygodial was found to maintain potency against apoptosis-resistant cancer cells as well as those displaying the multidrug-resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal-Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.
Source: ChemMedChem
Authors: Ramesh Dasari, Annelise De Carvalho, Derek C. Medellin, Kelsey N. Middleton, Frédéric Hague, Marie N. M. Volmar, Liliya V. Frolova, Mateus F. Rossato, Jorge J. De La Chapa, Nicholas F. Dybdal‐Hargreaves, Akshita Pillai, Véronique Mathieu, Snezna Rogelj, Cara B. Gonzales, João B. Calixto, Antonio Evidente, Mathieu Gautier, Gnanasekar Munirathinam, Rainer Glass, Patricia Burth, Stephen C. Pelly, Willem A. L. van Otterlo, Robert Kiss, Alexander Kornienko
Institutions: Texas State University, Université Libre de Bruxelles, Laboratoire de physiologie cellulaire et moléculaire, Université de Picardie Jules Verne, Ludwig-Maximilians-Universität München, New Mexico Institute of Mining and Technology, Universidade Federal de Santa Catarina, The University of Texas at San Antonio Health Science Center, University of Illinois Chicago, Rockford campus, University of Naples Federico II, Universidade Federal Fluminense, Stellenbosch University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
Awards: Notch signaling and anticancer drug sensitivity in oral squamous cell carcinoma, Institute for Integration of Medicine & Science: A Partnership to Improve Health, G380793897, G4023307058, G4744606257, Mode of Action of the Amaryllidaceae Alkaloid Lycorine-Promising Anticancer Agent, G8759028581, Craniofacial Oral-biology Student Training in Academic Research (COSTAR), New Mexico IDeA Networks of Biomedical Research Excellence (INBRE)
OpenAlex ID: W2178197654