Background: Diabetes mellitus is a challengeable metabolic disorder that leads to a group of complications when the HbA1c level is not maintained. Most of the existing drugs available in the market in long-term use may lead to serious adverse effects. Hence, current research focuses on drug development for the management of diabetes by synthesizing natural mimicking flavonoid analogues.

Objective: This study focused on the synthesis of flavanone derivatives imitating natural flavonoid core and investigated for their antidiabetic and antioxidant activity, which can help in the development of drug discovery targeting diabetic management.

Materials and Methods: The novel 2-phenyl-2,3-dihydro-chromen-4-ones were synthesized from 1,3-diphenyl-prop-2-en-1-one derivatives and characterized using UV, IR, ¹HNMR, ¹³CNMR and mass spectroscopic techniques. Drug target site was determined using graph theoretical analysis and screened the characterized title compounds for their in-silico studies by analyzing their physiochemical properties, ADMET studies, and molecular docking analysis. Antidiabetic and free radical scavenging effects were investigated both by in-vitro (alpha-amylase inhibitory assay) and in-vivo models. Streptozotocin (STZ) induced rats were used as in-vivo models.

Results: The α-amylase inhibitory assay showed flavanones with hydroxyl substitution HFA1- HFA7 had significant IC50 values. The test compounds (HFA3-HFA7) were investigated for their antidiabetic activity on STZ induced rats at 40 mg/kg. The blood glucose level and antioxidant enzymes were significantly restored by title compounds (HFA5, HFA4, and HFA6) with an electron-donating group such as hydroxyl, methoxy and thiophenyl group on ring B compared to glibenclamide.

Conclusion: These results suggest that naturally mimicking synthesized flavanone have antidiabetic and antioxidant properties, which can aid in the development of drugs towards diabetes management.

背景：糖尿病是一种具有挑战性的代谢紊乱，当 HbA1c 水平无法维持时会导致一组并发症。市场上现有的大多数药物长期使用可能会导致严重的不良反应。因此，目前的研究重点是通过合成天然的类黄酮类似物来开发治疗糖尿病的药物。

目的：本研究的重点是合成仿天然黄酮核心的黄烷酮衍生物，并研究其抗糖尿病和抗氧化活性，这有助于开发针对糖尿病管理的药物发现。

材料和方法：新型 2-苯基-2,3-二氢-chromen-4-ones 由 1,3-二苯基-prop-2-en-1-one 衍生物合成，并使用 UV、IR、¹ HNMR、¹³ CNMR 和质谱技术。使用图论分析确定药物靶点，并通过分析其理化性质、ADMET 研究和分子对接分析筛选表征的标题化合物进行计算机内研究。通过体外（α-淀粉酶抑制试验）和体内模型研究了抗糖尿病和自由基清除作用。链脲佐菌素 (STZ) 诱导的大鼠被用作体内模型。

结果：α-淀粉酶抑制试验表明，羟基取代 HFA1-HFA7 的黄烷酮具有显着的 IC50 值。研究了测试化合物 (HFA3-HFA7) 在 40mg/kg 时对 STZ 诱导的大鼠的抗糖尿病活性。与格列本脲相比，在 B 环上具有供电子基团（如羟基、甲氧基和噻吩基）的标题化合物（HFA5、HFA4 和 HFA6）可显着恢复血糖水平和抗氧化酶。

结论：这些结果表明，天然模拟合成的黄烷酮具有抗糖尿病和抗氧化特性，有助于开发治疗糖尿病的药物。