Anti-Diabetic Natural Chalcones: Protein Tyrosine Phosphatase-1B (PTP-1B) Inhibitors

Abstract

Diabetes Mellitus is exclusively characterized by enhanced plasma sugar levels along with several groups of heterogeneous disorders such as alteration in the metabolism of proteins, carbohydrates, and lipids. Present-day studies have indicated that PTP1B-knockout animals demonstrated improved glucose tolerance, reduction in diet-induced obesity, and enhanced sensitivity of cells towards insulin. For meeting the need for better PTP-1B inhibitors in the current scenario, natural chalcones have been recently been identified in the management of major diabetic complications with better selectivity and also without any pharmacokinetic compromise. The natural product chalcone-based inhibitors are not under clinical use and they are not explored clinically in terms of toxicological profiles to develop a suitable formulation. The review article has comprehensively focused on some very unknown natural chalcone compounds (kuwanon J, kuwanon R, kuwanon V, isoliquiritigenin, xanthoangelol, xanthoangelol D, xanthoangelol E, xanthoangelol F, xanthoangelol K, 4-hydroxyderricin, 5,4’-dihydroxy-6,7-furanbavachalcone, licochalcone A, licochalcone B, licochalcone C, licochalcone D, licochalcone E, echinatin, laxichalcone, broussochalcone, macdentichalcone, (2E)-1-(5,7-dihydroxy-2,2-dimethyl-2H-benzopyran-8-yl)-3-phenyl-2-propen-1-one, (2E)-1-(5,7-dihydroxy-2,2,6-trimethyl-2H-benzopyran-8-yl)-3-(4-methoxyphenyl)-2-propen-1-one, and abyssinone-VI-4-O-methyl ether) having tremendous potential to exhibit anti-diabetic activity by selectively modulating the promising therapeutic target protein tyrosine phosphatase 1B (PTP-1B) that will prevent the degradation of insulin. In modern days, these natural product chalcone-based PTP-1B inhibitors are not under clinical use and they have not received any such attention in modern-day medicine as they are not explored clinically in terms of toxicological profiles to develop a suitable formulation. In the near future, it is expected that these chalcone based PTP-1B inhibitors will open new avenues of diabetotherapeutics.