School of Pharmacy, Maharaja Agrasen University, Atal Shiksha Kunj, Kalujhanda, Dist. Solan, 174103, Himachal Pradesh, India.
Department of Pharmaceutical Chemistry, Shivalik College of Pharmacy, Nangal, Dist. Rupnagar, 140126, Punjab, India.
Med Chem. 2021;17(4):369-379. doi: 10.2174/1573406416666200512073640.
To develop novel compounds having potent anticancer and antibacterial activities.
Several studies have proved that benzylidene analogues of clinical 2,4-TZDs, such as troglitazone and ciglitazone, have more potent antiproliferative activity than their parent compounds. Literature studies also revealed that the attachment of more heterocyclic rings, containing nitrogen on 5th position of 2,4-TZD, can enhance the antimicrobial activity. Hence, attachment of various moieties on the benzylidene ring may produce safe and effective compounds in the future.
The objective of the present study was to synthesize a set of novel benzylidene ring containing 5- and 3-substituted-2,4-thiazolidinedione derivatives and evaluate them for their anticancer and antibacterial activity.
The synthesized compounds were characterized by IR, NMR, mass, and elemental studies. The in vitro cytotoxicity studies were performed for human breast cancer (MCF-7) and human lung cancer (A549) cells and HepG2 cell-line and compared to standard drug doxorubicin by MTT assay. Antimicrobial activity of the synthesized 2,4-thiazolidinediones derivatives was carried out using the cup plate method with slight modification.
The results obtained showed that TZ-5 and TZ-13 exhibited good antiproliferative activity against A549 cancer cell-line, whereas TZ-10 exhibited moderate antiproliferative activity against HepG2 cell-line when compared to standard drug doxorubicin. TZ-5 also exhibited reasonable activity against the MCF-7 cell-line with doxorubicin as standard. TZ-4, TZ-5, TZ-6, TZ-7, and TZ- 16 exhibited remarkable antibacterial activity against Gram positive and moderate activity against Gram negative bacteria with the standard drug ciprofloxacin.
Attachment of heterocyclic rings containing nitrogen as the hetero atom improves the anticancer and antimicrobial potential. Attachment of electronegative elements like halogens can also enhance the antimicrobial activity. Further structure modifications may lead to the development of more potent 2,4-TZD leads that can be evaluated for further advanced studies.
开发具有强效抗癌和抗菌活性的新型化合物。
多项研究证实，临床 2,4-TZDs 的苯亚甲基类似物，如曲格列酮和 ciglitazone，比其母体化合物具有更强的抗增殖活性。文献研究还表明，在 2,4-TZD 的第 5 位上连接更多含氮的杂环可以增强抗菌活性。因此，在苯亚甲基环上连接各种取代基可能会产生安全有效的化合物。
本研究的目的是合成一组新型含 5-和 3-取代的 2,4-噻唑烷二酮衍生物的苯亚甲基，并评估它们的抗癌和抗菌活性。
通过 IR、NMR、质谱和元素分析对合成的化合物进行了表征。通过 MTT 法对人乳腺癌（MCF-7）和人肺癌（A549）细胞和 HepG2 细胞系进行了体外细胞毒性研究，并与标准药物多柔比星进行了比较。采用稍加改进的杯盘法对合成的 2,4-噻唑烷二酮衍生物的抗菌活性进行了测定。
结果表明，与标准药物多柔比星相比，TZ-5 和 TZ-13 对 A549 癌细胞系表现出良好的抗增殖活性，而 TZ-10 对 HepG2 细胞系表现出中等的抗增殖活性。TZ-5 对 MCF-7 细胞系也表现出与多柔比星相当的活性。TZ-4、TZ-5、TZ-6、TZ-7 和 TZ-16 对革兰氏阳性菌表现出显著的抗菌活性，对革兰氏阴性菌也表现出中等的抗菌活性，与标准药物环丙沙星相当。
杂环中含氮的杂原子的连接提高了抗癌和抗菌的潜力。连接电负性元素，如卤素，也可以增强抗菌活性。进一步的结构修饰可能会导致开发出更有效的 2,4-TZD 先导化合物，这些先导化合物可以进一步进行深入研究。
