Unlocking the Potential of Calophyllum Xanthones: A Review on Antileukemic Activity and Molecular Docking Insights

Source abstract

The genus Calophyllum, a member of the Calophyllaceae family, has garnered increasing scientific attention due to its pharmacologically active constituents, particularly xanthones. This review consolidates current findings on xanthones isolated from Malaysian Calophyllum species, emphasizing their antileukemic potential. A total of 72 xanthones have been reported across various species, with the majority derived from stem bark and roots. Several xanthones such as caloxanthone B, ananixanthone, and brasixanthone B exhibit remarkable cytotoxic activity against leukemia cell lines, notably K562. The review also evaluates molecular docking interactions of 41 structurally characterized xanthones with two critical leukemia-related protein targets: cyclin-dependent kinase 4 (CDK4) and matrix metalloproteinase-2 (MMP2). Docking simulations revealed that calozeyloxanthone, xanthochymone B, and caloxanthone J demonstrated strong binding affinities toward these targets, by surpassing standard inhibitors abemaciclib and batimastat in silico. These findings corroborate existing in vitro data and highlight the therapeutic potential of Calophyllum-derived xanthones as dual-target inhibitors. The review outlines key pharmacophores contributing to bioactivity and underscores the promise of Malaysian Calophyllum species as reservoirs for novel antileukemic agents. Further preclinical and clinical evaluations are warranted to validate their efficacy and develop structure-optimized derivatives for cancer therapy.