Exploring the Multitarget Therapeutic Potential of Mangostin Derivatives.

Abstract

Mangostins and their derivatives exhibit broad therapeutic potential, with structural modifications enhancing their efficacy against cancer, inflammation, neurodegenerative disorders, oxidative stress, and microbial infections. Modified derivatives have demonstrated improved effectiveness in cancer treatment. They exhibit potent anti- inflammatory effects for conditions like pulmonary fibrosis and Parkinson's disease and neuroprotective benefits through cholinesterase inhibition and protection against oxidative damage. For example, structural modifications of α-mangostin (1) significantly enhanced its cytotoxicity, with the 3,6-dibenzylated (4) derivative achieving three times greater efficacy against HL-60 cells and diacetyl (8) and benzoyl (9) derivatives and two- and four-fold improvements against HT-29 cells. The enhanced antioxidant properties of these derivatives improve radical scavenging, lipid protection, and metal ion binding. They possess antimicrobial properties against multidrug-resistant bacteria and fungi, with several derivatives exhibiting high membrane selectivity, low toxicity, and strong in vivo efficacy. Their antimalarial, antiparasitic, and antiviral activities further expand their therapeutic uses, including inhibition of viral proteases. Structural modifications of α-mangostin (1) show promising clinical applications, including enhanced cytotoxicity in cancer therapy with the 3,6-dibenzylated (4), diacetyl (8), and benzoyl (9) derivatives, potent anti-inflammatory activity with PDE4-targeting compound (43), and effective antimicrobial properties in derivatives (18 and 22) against multidrug-resistant infections.