Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives

Abstract

Xanthones represent a structurally diverse group of compounds with a broad range of biological and pharmacological activities, depending on the nature and position of various substituents in the dibenzo-γ-pyrone scaffold. Among the large number of natural and synthetic xanthone derivatives, carboxyxanthones are very interesting bioactive compounds as well as important chemical substrates for molecular modifications to obtain new derivatives. A remarkable example is 5,6-dimethylxanthone-4-acetic acid (DMXAA), a simple carboxyxanthone derivative, originally developed as an anti-tumor agent and the first of its class to enter phase III clinical trials. From DMXAA new bioactive analogues and derivatives were also described. In this review, a literature survey covering the report on carboxyxanthone derivatives is presented, emphasizing their biological activities as well as their application as suitable building blocks to obtain new bioactive derivatives. The data assembled in this review intends to highlight the therapeutic potential of carboxyxanthone derivatives and guide the design for new bioactive xanthone derivatives.

From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones

“…Considering that carboxyxanthone derivatives are appropriate chemical substrates to perform molecular modifications to obtain diverse derivatives and analogues [ 138 ], we selected different compounds, comprising one or more carboxylic groups, to perform the referred syntheses [ 68 , 135 , 136 , 137 ]. Both enantiomers of a variety of amino alcohols, amines, and amino esters were chosen as chiral building blocks, containing a primary amine as reactive group for amide formation ( Figure 17 ).…”

Study on Synthesis and Biological Evaluation of 3-Aryl Substituted Xanthone Derivatives as Novel and Potent Tyrosinase Inhibitors

“…Xanthones are a class of oxygen-containing heterocycles with γ-pyran moiety condensed with two benzene rings, which are widely distributed in nature. 18) In recent years, xanthone derivatives have been received considerable attention in the field of medicinal chemistry because of their diversely biological functions, 20,21) such as anti-oxidant, 22) anti-hypertensive, 23) anti-convulsant, 24) anti-cholinesterase, 25) anti-malarial, 26) antimicrobial, 27) anti-inflammatory, 28) and anti-cancer activities. 29) Besides, they also served as the effective inhibitors of several enzymes like α-glycosidase, 30,31) topoisomerase, 32) proteinkinase, 33) aromatase.…”

Synthesis of New Chiral Derivatives of Xanthones with Enantioselective Effect on Tumor Cell Growth and DNA Crosslinking

“…Carboxyxanthones have already proved to be suitable chemical substrates to obtain diverse derivatives and analogues . Carboxyxanthone 1 was chosen for the synthesis of new chiral xanthones since, in a previous study, afforded the more active derivatives in the growth inhibition of the tumor cell lines .…”