Karumanchi Srikanth Kumar, Atmakuri Lakshmana Rao, Mandava V Basaveswara Rao, Rajala Srikala
V. V. Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, Gudlavalleru, Andhra Pradesh, India.
Krishna University, Department of Chemistry, Machilipatnam, Andhra Pradesh, India.
Turk J Pharm Sci. 2019 Dec;16(4):380-391. doi: 10.4274/tjps.galenos.2018.82612. Epub 2019 Nov 11.
The aim was the synthesis of novel substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones and screening for their hypoglycemic activity and anti-inflammatory activity, as well as molecular docking studies to find out active potential lead molecules.
Substituted aromatic aldehydes, thiazolidine-2,4-dione, and morpholine on Mannich reaction gave the title compounds. They were characterized by physical and spectral methods. hypoglycemic activity was examined in alloxan induced Wistar albino rats by tail tipping method. anti-inflammatory activity was tested by human red blood cell (HRBC) membrane stabilization and protein denaturation. Using AutoDock, molecular docking studies were carried out to find out the best fit ligands.
Series of substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones were synthesized and chemically they were confirmed by spectral techniques. Acute toxic studies of hypoglycemic activity results revealed that compounds 4c, 4h, and 4n exhibited good activity at 35 mg/kg body weight. Chronic toxic study results indicated that compounds 4h and 4n exhibited good activity at 70 mg/kg body weight. Anti-inflammatory activity results indicated the highest inhibition was shown by compounds 4k and 4f at 500 μg/mL in HRBC membrane stabilization. In protein denaturation, the highest inhibition was shown by compound 4k at 500 μg/mL. In molecular docking studies, compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX-1 and COX-2 actives sites.
Microwave irradiation produced high yield in short reaction times. The presence of electron releasing groups at the para position of the phenyl ring may give the ability to produce hypoglycemic activity and the presence of electron withdrawing groups at the para position of the phenyl ring causes anti-inflammatory activity. The results showed that some compounds exhibited good hypoglycemic and anti-inflammatory activities. Compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX isoenzymes' active sites in molecular docking studies.
合成新型取代的5-[吗啉基（苯基）甲基]-噻唑烷-2,4-二酮，并筛选其降血糖活性和抗炎活性，以及进行分子对接研究以找出具有活性潜力的先导分子。
取代的芳香醛、噻唑烷-2,4-二酮和吗啉通过曼尼希反应得到目标化合物。通过物理和光谱方法对其进行表征。采用断尾法在四氧嘧啶诱导的Wistar白化大鼠中检测降血糖活性。通过人红细胞（HRBC）膜稳定化和蛋白质变性试验检测抗炎活性。使用AutoDock进行分子对接研究以找出最佳匹配配体。
合成了一系列取代的5-[吗啉基（苯基）甲基]-噻唑烷-2,4-二酮，并通过光谱技术对其进行了化学确认。降血糖活性的急性毒性研究结果表明，化合物4c、4h和4n在体重35 mg/kg时表现出良好活性。慢性毒性研究结果表明，化合物4h和4n在体重70 mg/kg时表现出良好活性。抗炎活性结果表明，在HRBC膜稳定化试验中，化合物4k和4f在500 μg/mL时表现出最高抑制率。在蛋白质变性试验中，化合物4k在500 μg/mL时表现出最高抑制率。在分子对接研究中，化合物4h和4n在PPARγ受体蛋白上表现出更高的结合亲和力，化合物4k在COX-1和COX-2活性位点表现出更高的结合亲和力。
微波辐射在短反应时间内产生了高产率。苯环对位存在供电子基团可能赋予产生降血糖活性的能力，而苯环对位存在吸电子基团则导致抗炎活性。结果表明，一些化合物表现出良好的降血糖和抗炎活性。在分子对接研究中，化合物4h和4n在PPARγ受体蛋白上表现出更高的结合亲和力，化合物4k在COX同工酶活性位点表现出更高的结合亲和力。
