Tahlan Sumit, Verma Prabhakar Kumar
Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.
Chem Cent J. 2018 Dec 4;12(1):129. doi: 10.1186/s13065-018-0496-0.
Thiazolidinedione is a pentacyclic moiety having five membered unsaturated ring system composed with carbon, oxygen, nitrogen and sulfur molecules at 1 and 3 position of the thiazole ring and widely found throughout nature in various form. They favourably alter concentration of the hormones secreted by adipocytes, particularly adiponectin. They also increase total body fat and have mixed effects on circulating lipids. Thiazolidinedione nucleus is present in numerous biological moieties and has different pharmacological activities likes, e.g. antimalarial, antimicrobial, antimycobacterial, anticonvulsant, antiviral, anticancer, anti-inflammatory, antioxidant, anti-HIV (human immunodeficiency virus) and antituberculosis.
The synthesized compounds were screened for their in vitro antimicrobial potential against Gram (positive and negative) bacterial and fungal strains by tube dilution technique. In this series, compound 10 exhibited significant antimicrobial activity against B. subtilis and S. aureus with MIC = 4.2 × 10 µM/ml, compound 15 showed significant activity against K. pneumonia with MIC = 2.60 × 10 µM/ml and compound 4 displayed potent antibacterial activity against E. coli with MIC = 4.5 × 10 µM/ml. Compound 10 had most potent antifungal activity against C. albicans and A. niger with MIC = 4.2 × 10 µM/ml. Compounds 12 and 15 were found as most active antidiabetic agents having IC = 27.63 μg/ml and 22.35 μg/ml, respectively, using DPPH assay. Antioxidant activity results indicated that compounds 3 and 9 displayed good antioxidant agent with IC = 29.04 μg/ml and 27.66 μg/ml respectively, using α amylase assay.
All the synthesized derivatives exhibited good antimicrobial, antidiabetic and antioxidant activities using specific methods then compared with mentioned standard drugs. Especially, compounds 3, 4, 9, 10, 12 and 15 displayed highest activity. Structure activity relationship demonstrated that presence of electron withdrawing group (o-NO, p-Cl, p-Br) enhanced the antibacterial activity against E. coli as well as increased the antioxidant activity while the presence of electron releasing group (o/p-OCH, 3,4,5-trimethoxy) enhanced the antibacterial activity against S. aureus, B. subtilis, S. typhi, K. pneumonia, C. albicans and A. niger as well as the antidiabetic activity.
噻唑烷二酮是一种五环部分，具有由碳、氧、氮和硫分子组成的五元不饱和环系统，位于噻唑环的1位和3位，以各种形式广泛存在于自然界中。它们有利地改变脂肪细胞分泌的激素浓度，特别是脂联素。它们还会增加全身脂肪，并对循环脂质产生混合影响。噻唑烷二酮核存在于众多生物部分中，并具有不同的药理活性，如抗疟疾、抗菌、抗分枝杆菌、抗惊厥、抗病毒、抗癌、抗炎、抗氧化、抗HIV（人类免疫缺陷病毒）和抗结核。
通过试管稀释技术筛选合成化合物对革兰氏（阳性和阴性）细菌和真菌菌株的体外抗菌潜力。在该系列中，化合物10对枯草芽孢杆菌和金黄色葡萄球菌表现出显著的抗菌活性，MIC = 4.2×10 μM/ml，化合物15对肺炎克雷伯菌表现出显著活性，MIC = 2.60×10 μM/ml，化合物4对大肠杆菌表现出强效抗菌活性，MIC = 4.5×10 μM/ml。化合物10对白色念珠菌和黑曲霉具有最强的抗真菌活性，MIC = 4.2×10 μM/ml。使用DPPH测定法发现化合物12和15是最具活性的抗糖尿病药物，IC分别为27.63 μg/ml和22.35 μg/ml。抗氧化活性结果表明，使用α淀粉酶测定法，化合物3和9分别以IC = 29.04 μg/ml和27.66 μg/ml表现出良好的抗氧化剂活性。
与上述标准药物相比，所有合成衍生物使用特定方法均表现出良好的抗菌、抗糖尿病和抗氧化活性。特别是，化合物3、4、9、10、12和15表现出最高活性。构效关系表明，吸电子基团（邻硝基、对氯、对溴）的存在增强了对大肠杆菌的抗菌活性，并提高了抗氧化活性，而供电子基团（邻/对甲氧基, 3,4,5-三甲氧基）的存在增强了对金黄色葡萄球菌、枯草芽孢杆菌、伤寒沙门氏菌、肺炎克雷伯菌、白色念珠菌和黑曲霉的抗菌活性以及抗糖尿病活性。
