A novel double active pharmaceutical ingredient (d-API), metforminium ibuprofenate (MtHIb) was synthesised by combining metformin hydrochloride (MtHCl) and sodium ibuprofen (NaIb). This formulation exhibits anti-diabetic and anti-inflammatory properties similar to its parent compounds, along with a remarkable antiproliferative effect on diverse cancer cells. The present study is aimed to analyse the anticancer potential of MtHIb by mouse tumour model and molecular docking. Solid tumour was induced by Dalton's Lymphoma Ascites (DLA) cells in Swiss albino mice, and d-API was administered orally. The tumour volume was measured using Vernier calliper and the activity of γ-glutamyl transferase (GGT) was assessed. The potential interactions of MtHIb with target proteins mTOR, HER2, EGFR, CDK4, CDK6, ERα/β, progesterone, COX2, BUB1, and KEAP2 were analyzed . A significant reduction in tumour size was observed in mice treated with MtHIb. On the 30 day, the tumour volume, which was 8.12 cm in untreated animals, decreased to 1.311 cm with the treatment of 5 mg/kg b.wt of MtHIb, representing an 83.8 % reduction. The activity of GGT, a marker enzyme of proliferative activity, was considerably reduced from 394.87 to 51.26 U/mg protein/L. Molecular docking studies indicated that MtHIb exhibited strong binding affinity towards all the screened target proteins, specifically HER2, EGFR, CDK4, and BUB1. The findings suggest that MtHIb has promising anti-tumour effect, as evidenced by its significant reduction in tumour size and GGT activity in mice. The strong binding affinity of MtHIb towards the key cancer related proteins further supports its potential as a therapeutic agent against cancer, particularly in targeting pathways involved in cell proliferation and survival. Further preclinical and clinical studies are required to validate these findings and to explore the full therapeutic potential of MtHIb in cancer treatment.

中文翻译：

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探索双活性药物成分布洛芬二甲双胍的抗癌潜力：整合体内和计算机研究


通过将盐酸二甲双胍 (MtHCl) 和布洛芬钠 (NaIb) 组合，合成了一种新型双活性药物成分 (d-API)——布洛芬二甲双胍 (MtHIb)。该配方表现出与其母体化合物类似的抗糖尿病和抗炎特性，并对多种癌细胞具有显着的抗增殖作用。本研究旨在通过小鼠肿瘤模型和分子对接分析MtHIb的抗癌潜力。在瑞士白化小鼠中通过道尔顿淋巴瘤腹水 (DLA) 细胞诱导实体瘤，并口服 d-API。使用游标卡尺测量肿瘤体积并评估γ-谷氨酰转移酶（GGT）的活性。分析了 MtHIb 与靶蛋白 mTOR、HER2、EGFR、CDK4、CDK6、ERα/β、孕酮、COX2、BUB1 和 KEAP2 的潜在相互作用。在接受 MtHIb 治疗的小鼠中观察到肿瘤大小显着减小。第 30 天，未治疗动物的肿瘤体积为 8.12 cm3，经过 5 mg/kg b.wt 的 MtHIb 治疗后，肿瘤体积减少至 1.311 cm3，减少了 83.8%。增殖活性标记酶 GGT 的活性从 394.87 U/mg 蛋白/L 大幅降低至 51.26 U/mg 蛋白/L。分子对接研究表明，MtHIb 对所有筛选的靶蛋白，特别是 HER2、EGFR、CDK4 和 BUB1 表现出很强的结合亲和力。研究结果表明，MtHIb 具有良好的抗肿瘤作用，其显着减小小鼠肿瘤大小和 GGT 活性就证明了这一点。 MtHIb 对关键癌症相关蛋白的强结合亲和力进一步支持了其作为癌症治疗剂的潜力，特别是在靶向细胞增殖和存活相关途径方面。 需要进一步的临床前和临床研究来验证这些发现并探索 MtHIb 在癌症治疗中的全部治疗潜力。