Synthesis and Antiproliferative Activity of Novel Heterocyclic Glycyrrhetinic Acid Derivatives

Abstract

A new series of glycyrrhetinic acid derivatives has been synthesized via the introduction of different heterocyclic rings conjugated with an α,β-unsaturated ketone in its ring A. These new compounds were screened for their antiproliferative activity in a panel of nine human cancer cell lines. Compound 10 was the most active derivative, with an IC50 of 1.1 µM on Jurkat cells, which is 96-fold more potent than that of glycyrrhetinic acid, and was 4-fold more selective toward that cancer cell line. Further biological studies performed in Jurkat cells showed that compound 10 is a potent inducer of apoptosis that activates both the intrinsic and extrinsic pathways.

Biotransformation of Oleanane and Ursane Triterpenic Acids

“…Molecules 2020, 25, x FOR PEER REVIEW 2 of 34 [8][9][10][11]. An alternative way to obtain valuable derivatives is by biotransformation under normal and environmentally friendly conditions employing the catalytic activity of microorganisms with high regio-and stereoselectivity in one technological stage.…”

“…Henceforth, the interest in the topic discussed has been increasing and the Active Triterpenoid Biocatalysts List has been expanded every year, as is the number of various bioactive triterpenic derivatives formed via biotransformations [30][31][32]. Now, preparation of biologically active compounds based on pentacyclic triterpenoids is an actual research discussed in plenty of experimental and review publications [8,12,[32][33][34]. However, the reviews are overwhelmingly focused on chemical transformations or describe specific types of biological activities of triterpenoids.…”

“…At present, one of the most common ways to increase the effectiveness and bioavailability of triterpenoids is by chemical modification. This usually requires high temperature and pH, use of expensive reagents, and introduction of protective groups of molecule reactive centers [ 8 , 9 , 10 , 11 ]. An alternative way to obtain valuable derivatives is by biotransformation under normal and environmentally friendly conditions employing the catalytic activity of microorganisms with high regio- and stereoselectivity in one technological stage.…”

“…Now, preparation of biologically active compounds based on pentacyclic triterpenoids is an actual research discussed in plenty of experimental and review publications [ 8 , 12 , 32 , 33 , 34 ]. However, the reviews are overwhelmingly focused on chemical transformations or describe specific types of biological activities of triterpenoids.…”

Design, synthesis and biological evaluation of novel amide-linked 18β-glycyrrhetinic acid derivatives as novel ALK inhibitors

“…[4][5][6] The 18b-GA nucleus, a feasible structure for in-depth pharmaceutical exploration and for development of new potential antiproliferative drug candidates, has aroused extensive attention from medicinal chemists over the last decade. [7][8][9][10][11] The presence of polar functional groups (C3-OH and C30-COOH) in its structure could impact the biological activities of the mentioned analogues. 12 Inspired by the mentioned developments and facts, our previous work was continued in structural modication of 18b-GA. 7 In the present study, substituted piperazine amide fragments were introduced into the C30-COOH of 18b-GA, and a novel series of amide-linked derivatives was designed as potential antitumor inhibitors.…”