AIM This study aimed at screening and development of TG2 inhibitors as anti lung cancer agent. BACKGROUND Transglutaminase 2 (TG2) is multifunctional and ubiquitously expressed protein from the transglutaminase family. It takes part in various cellular processes and plays an important role in the pathogenesis of autoimmune, neurodegerative diseases, and also cancer. OBJECTIVE The proposed study focused on screening potent inhibitors of TG2 by in-silico method and synthesize their derivative as well as analyse its activity by utilizing an in-vitro approach. MATERIALS AND METHODS Molecular docking studies have been carried out on the different classes of TG2 inhibitors against the target protein. Nearly thirty TG2 inhibitors were selected from literature and docking was performed against transglutaminase 2. The computational ADME property screening was also carried out to check their pharmacokinetic properties. The compounds which exhibited positive ADME properties with good interaction while possessing the least binding energy were further validated for their anti-lung cancer inhibition property against A549 cell lines using cytotoxicity studies. RESULTS The results of the present study indicate that the docked complex formed by cystamine showed better binding affinity towards target protein, so this derivative of cystamine was formed using 2,5 dihydrobenzoic acid. Invitro results revealed that both molecules proved to be good cytotoxic agents against A549 lung cancer (875.10, 553.22 μg/ml), respectively. Further, their activity needs to be validated on TG2 expressing lung cancer. CONCLUSION Cystamine and its derivative can act as a potential therapeutic target for lung cancer but its activity should be further validated on TG2 expressing lung cancer.

中文翻译：

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通过计算机和体外方法筛选和开发转谷氨酰胺酶-2 抑制剂及其衍生物作为抗肺癌药物。

目的本研究旨在筛选和开发作为抗肺癌药物的TG2抑制剂。背景转谷氨酰胺酶2(TG2)是来自转谷氨酰胺酶家族的多功能且普遍表达的蛋白质。它参与各种细胞过程，并在自身免疫、神经退行性疾病和癌症的发病机制中发挥重要作用。目的 本研究的重点是通过计算机内方法筛选有效的 TG2 抑制剂，并利用体外方法合成它们的衍生物并分析其活性。材料和方法 对不同类别的 TG2 抑制剂针对靶蛋白进行了分子对接研究。从文献中筛选出近三十种 TG2 抑制剂，并针对转谷氨酰胺酶 2 进行对接。还进行了计算 ADME 特性筛选以检查它们的药代动力学特性。使用细胞毒性研究进一步验证了具有良好相互作用的积极 ADME 特性同时具有最低结合能的化合物对 A549 细胞系的抗肺癌抑制特性。结果本研究结果表明，胱胺形成的对接复合物对靶蛋白具有较好的结合亲和力，因此该胱胺衍生物是用2，5-二氢苯甲酸形成的。体外结果显示，这两种分子分别被证明是抗 A549 肺癌的良好细胞毒剂（875.10, 553.22 μg/ml）。此外，它们的活性需要在表达 TG2 的肺癌上进行验证。