Synthesis and Biological Activity of Triterpene–Coumarin Conjugates

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2021-05, Vol.84 (5), p.1587-1597
• Main Authors: Vega-Granados, Karina, Medina-O’Donnell, Marta, Rivas, Francisco, Reyes-Zurita, Fernando J, Martinez, Antonio, Alvarez de Cienfuegos, Luis, Lupiañez, Jose A, Parra, Andres
• Format: Article
• Language: English
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.1c00128

A set of 12 maslinic acid–coumarin conjugates was synthesized, with 9 being maslinic acid–diamine–coumarin conjugates at the C-28 carboxylic acid group of triterpene acid and the other three being maslinic acid–coumarin conjugates at C-2/C-3 and/or C-28 of the triterpene skeleton. The cytotoxic effects of these 12 triterpene conjugates were evaluated in three cancer cell lines (B16-F10, HT29, and Hep G2) and compared, respectively, with three nontumor cell lines from the same or similar tissue (HPF, IEC-18, and WRL68). The most potent cytotoxic results were achieved by a conjugate with two molecules of coumarin-3-carboxylic acid coupled through the C-2 and C-3 hydroxy groups of maslinic acid. This conjugate showed submicromolar IC50 values in two of the three cancer cell lines tested (0.6, 1.1, and 0.9 μM), being between 110- and 30-fold more effective than its corresponding precursor. Furthermore, this conjugate (10) showed percentages of cell viability for the three nontumor lines of 90%. Four maslinic acid–coumarin conjugates displayed apoptotic effects in the treated cells, with total apoptosis rates of between 40 and 85%, relative to the control. Almost all the compounds assayed caused cell-cycle arrest in all cancer cell lines, increasing the number of these cells in the G0/G1 phase.