Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884, Nasr City, Cairo, Egypt.
Pharmaceutical Organic Chemistry Department, College of Pharmacy, Misr University for Science and Technology (MUST), 6th October City, Egypt.
Mol Divers. 2021 Feb;25(1):291-306. doi: 10.1007/s11030-020-10070-w. Epub 2020 Mar 12.
Many shreds of evidence have recently correlated A2B receptor antagonism with anticancer activity. Hence, the search for an efficient A2B antagonist may help in the development of a new chemotherapeutic agent. In this article, 23 new derivatives of [1,2,4]triazolo[4,3-a]quinoxaline were designed and synthesized and its structures were confirmed by different spectral data and elemental analyses. The results of cytotoxic evaluation of these compounds showed six promising active derivatives with IC values ranging from 1.9 to 6.4 μM on MDA-MB 231 cell line. Additionally, molecular docking for all synthesized compounds was performed to predict their binding affinity toward the homology model of A2B receptor as a proposed mode of their cytotoxic activity. Results of molecular docking were strongly correlated with those of the cytotoxic study. Finally, structure activity relationship analyses of the new compounds were explored.
最近有许多证据表明 A2B 受体拮抗作用与抗癌活性有关。因此，寻找有效的 A2B 拮抗剂可能有助于开发新的化疗药物。在本文中，设计并合成了 23 种[1,2,4]三唑并[4,3-a]喹喔啉的新衍生物，并通过不同的光谱数据和元素分析确认了其结构。这些化合物的细胞毒性评价结果表明，有 6 种具有 promising active 的衍生物对 MDA-MB 231 细胞系的 IC 值在 1.9 到 6.4 μM 之间。此外，对所有合成的化合物进行了分子对接，以预测它们与 A2B 受体同源模型的结合亲和力，作为其细胞毒性活性的一种假设模式。分子对接的结果与细胞毒性研究结果密切相关。最后，对新化合物的构效关系进行了探讨。
