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Oxoaporphine-Metformin Rhodium(III) Mixed Complex Achieving Dual Antidiabetes and Anticancer Effects by Interfering
Kun Yang1, Qi-Yuan Yang1, Kai-Jie Yang1
1Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
None:
The clinical convergence of type 2 diabetes mellitus (T2DM) and bladder cancer presents a unique therapeutic challenge. We developed a metal-based approach through rational integration of glucose-modulating metformin (Met) with a bioactive oxoaporphine alkaloid in the form of novel rhodium(III) complexes (Rh-Met). This first-reported hybrid metallodrug achieved dual therapeutic efficacy by simultaneously suppressing PI3K/AKT/mTOR signaling to reprogram glucose metabolism in cancer cells and restoring glycemic balance. In a clinically relevant T2DM-tumor model, Rh-Met exhibited a coordination synergistic effect and suppressed tumor progression while reducing hyperglycemia through disruption of energy homeostasis. Our findings demonstrated a paradigm-shifting strategy for concurrent management of diabetes and cancer via precision design of metallodrugs, highlighting the translational potential of metal complexes in comorbid disease therapy.
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