审查新的 2,5-双 (2,2,2-三氟乙氧基) 苯基连接的 1,3-噻唑烷-4-酮衍生物作为 AURKA 和 VEGFR-2 抑制剂抗神经胶质瘤药物，协助体外和计算机研究,ACS Omega

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审查新的 2,5-双 (2,2,2-三氟乙氧基) 苯基连接的 1,3-噻唑烷-4-酮衍生物作为 AURKA 和 VEGFR-2 抑制剂抗神经胶质瘤药物，协助体外和计算机研究
ACS Omega ( IF 3.7 ) Pub Date : 2023-11-10 , DOI: 10.1021/acsomega.3c04662
Sathyanarayana D Shankara ₁ , Arun M Isloor ₁ , Pavan K Jayaswamy ₂ , Praveenkumar Shetty _{2,

3} , Debashree Chakraborty ₄ , Pushyaraga P Venugopal ₄

Affiliation

通过计算开发和评估了具有 2,5-双（2,2,2-三氟乙氧基）苯基部分的 1,3-噻唑烷-4-酮衍生物的生物活性。所有合成的噻唑烷-4-酮衍生物的化学结构均使用多种方法进行了表征，包括核磁共振（NMR）（¹ H 和¹³ C）、高分辨率质谱（HRMS）和傅里叶变换红外（ FTIR）辐射。使用人胶质母细胞瘤癌细胞系（LN229）来研究纯化衍生物的抗胶质瘤功效。分别通过MTT、集落形成和隧道试验，评估了这些化合物的体外细胞毒性和凋亡作用。发现噻唑烷-4-酮衍生物5b、5c和5e在所有这些化合物中对胶质母细胞瘤细胞具有最佳功效。测定衍生物5b、5c和5e各自的IC ₅₀值为9.48、12.16和6.43g/mL。计算结果表明化合物的生物活性评价显着。桥连-NH基团与合成衍生物5b、5c、5d、5e和5h的Glu 260形成氢键。绝大多数新开发的化合物遵循Lipinski五法则，这与ADMET模型预测的结果一致。此外，对合成的化合物进行了针对蛋白质 AURKA 和 VEGFR-2 的分子对接评估和分子动力学模拟研究，以纳入计算机和体外数据。结果表明，几乎所有化合物都与 AURKA 和 VEGFR-2 残基具有相当大的结合，结合亲和力范围为 -9.8 至 -7.9 kcal/mol。因此，生物学研究和对接分数的结果表明，含有4-氯苯基取代基的噻唑烷酮分子5e可被认为是胶质母细胞瘤癌症治疗的潜在部分。

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Vetting of New 2,5-Bis (2,2,2-trifluoroethoxy) Phenyl-Linked 1,3-Thiazolidine-4-one Derivatives as AURKA and VEGFR-2 Inhibitor Antiglioma Agents Assisted with In Vitro and In Silico Studies

The bioactivity of 1,3-thiazolidin-4-one derivatives with a 2,5-bis (2,2,2-trifluoroethoxy) phenyl moiety was computationally developed and evaluated. All of the synthesized thiazolidin-4-one derivatives have their chemical structures characterized using a variety of methods, including nuclear magnetic resonance (NMR) (¹H and ¹³C), high-resolution mass spectrometry (HRMS), and Fourier transform infrared (FTIR) radiation. A human glioblastoma cancer cell line (LN229) was used to investigate the purified derivatives’ antiglioma cancer efficacy. By using the MTT, colony formation, and tunnel tests, respectively, the in vitro cytotoxic and apoptotic effects of these compounds were assessed. Thiazolidin-4-one derivatives 5b, 5c, and 5e were discovered to have the best efficacy against glioblastoma cells out of all of these compounds. The derivatives 5b, 5c, and 5e were determined to have respective IC₅₀ values of 9.48, 12.16, and 6.43 g/mL. Computation results showed that the bioactivity evaluations of the compounds were quite significant. The bridging –NH group forms a hydrogen bond with Glu 260 of synthesized derivatives 5b, 5c, 5d, 5e, and 5h. The vast majority of freshly developed compounds obeyed Lipinski’s rule of five, which is in line with the results that the ADMET model predicted. Additionally, molecular docking evaluation and molecular dynamics simulation investigations against the proteins AURKA and VEGFR-2 were conducted for the synthesized compounds to incorporate both in silico and in vitro data. The findings revealed that almost all of the compounds had considerable binding to AURKA and VEGFR-2 residues, with binding affinities ranging from −9.8 to −7.9 kcal/mol. Consequently, the results of the biological investigations and the docking scores demonstrated that thiazolidinone molecule 5e containing 4-chlorophenyl substituent may be considered as a potential moiety for glioblastoma cancer treatments.

更新日期：2023-11-10

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