Novel mangiferin derivatives attenuate adipogenesis in 3T3-L1 preadipocytes and ameliorate diet induced obesity in C57BL/6J mice†

Mangiferin with a xanthone scaffold exhibited potent anti-obesity activities and thus has attracted interest. However, some shortcomings, including limited solubility and moderate potency, restrict its application. To develop novel and efficient anti-obesity agents, a series of mangiferin (MGF) amino acid derivatives were synthesized, optimized and evaluated for anti-obesity activities in vitro and in vivo. Among these derivatives, G1 was identified to be a promising compound. G1 showed better liposolubility compared to MGF. In 3T3-L1 preadipocytes, G1 significantly inhibited cell differentiation and reduced fat accumulation by increasing inhibitory activity on fatty acid synthase, and triggering G0/G1 phase cell cycle arrest and production of intracellular reactive oxygen species. The intraperitoneal administration of G1 (30, 60 mg kg⁻¹/2 days) significantly inhibited body, liver and fat tissue weight gain, reduced lipid dysfunction, and ameliorated pathological characteristics in high-fat diet induced C57BL/6J obese mice. These results suggest that compound G1 may warrant further investigation as a promising anti-obesity agent for the treatment of human obesity.