Suryawanshi Ravikiran Maheshrao, Shimpi Rupali Bhalchandra, Muralidharan V, Nemade Lalita Shashikant, Gurugubelli Simhachalam, Baig Shahajan, Vikhe Sunayana Rahul, Dhawale Sachin A, Mortuza Mohammad Rakib, Sweilam Sherouk Hussein, Siddiqui Falak A, Khan Sharuk L, Tutone Marco, Ahmad Irfan, Begh Md Zamshed Alam
Department of Industrial Pharmacy and Quality Assurance, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.
Department of Pharmacognosy, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.
Chem Biodivers. 2025 May;22(5):e202402738. doi: 10.1002/cbdv.202402738. Epub 2025 Jan 13.
Today the alarming situation of diabetes seeks innovative antidiabetic medications, especially those derived from natural sources, as natural substances are safer than manufactured pharmaceuticals. Therefore, this study investigated the inhibitory properties of mangiferin and friedelin against glucokinase (GK), dipeptidyl peptidase-IV (DPP-IV), α-amylase, and α-glucosidase using computational methods, in vitro enzyme assays, and in-depth ADMET analysis. The study utilized a computer-aided drug design approach to assess the potential therapeutic properties of mangiferin and friedelin as Type 2 diabetes mellitus (T2DM) therapeutic agents. Molecular docking studies' outcomes encouraged the evaluation of both compounds in in vitro enzymatic assays. The docking study results were validated with the help of molecular dynamics simulation. Mangiferin and friedelin showed that they activated GK 20% and 5% more than the basal activity of the enzyme, respectively. In the DPP-IV enzyme assay, mangiferin and friedelin demonstrated IC values (74.93 ± 0.71 and 110.64 ± 0.21 µg/mL, respectively) comparable with the reference compound sitagliptin. Moreover, mangiferin and friedelin showed IC comparable to acarbose against α-amylase (9.72 ± 0.15, 11.84 ± 0.06, and 10.19 ± 0.05 mg/mL, respectively). In the α-glucosidase enzyme assay, mangiferin, friedelin, and acarbose displayed 11.72 ± 0.10, 14.34 ± 0.02, and 9.14 ± 0.06 mg/mL of IC values, respectively. The compounds showed promising in silico ADMET and drug-likeness properties, with potential binding affinities with all enzymes. In vitro enzymatic assays showed mangiferin and friedelin activated GK 20% and 5% more than basal activity, with IC values comparable to acarbose.
如今，糖尿病的严峻形势促使人们寻求创新的抗糖尿病药物，尤其是那些源自天然来源的药物，因为天然物质比人工合成药物更安全。因此，本研究采用计算方法、体外酶分析和深入的ADMET分析，研究了芒果苷和蛇麻脂醇对葡萄糖激酶（GK）、二肽基肽酶-IV（DPP-IV）、α-淀粉酶和α-葡萄糖苷酶的抑制特性。该研究利用计算机辅助药物设计方法评估芒果苷和蛇麻脂醇作为2型糖尿病（T2DM）治疗剂 的潜在治疗特性。分子对接研究的结果促使对这两种化合物进行体外酶分析评估。对接研究结果借助分子动力学模拟得到了验证。芒果苷和蛇麻脂醇分别比该酶的基础活性多激活20%和5%的GK。在DPP-IV酶分析中，芒果苷和蛇麻脂醇的IC值（分别为74.93±0.71和110.64±0.21µg/mL）与参考化合物西他列汀相当。此外，芒果苷和蛇麻脂醇对α-淀粉酶的IC值与阿卡波糖相当（分别为9.72±0.15、11.84±0.06和10.19±0.05mg/mL）。在α-葡萄糖苷酶分析中，芒果苷、蛇麻脂醇和阿卡波糖的IC值分别为11.72±0.10、14.34±0.02和9.14±0.06mg/mL。这些化合物在计算机模拟的ADMET和类药性质方面表现出前景，与所有酶具有潜在的结合亲和力。体外酶分析表明，芒果苷和蛇麻脂醇比基础活性多激活20%和5%的GK，其IC值与阿卡波糖相当。
