The development of anticancer agents targeting EGFR represents a promising strategy in the field of medicinal chemistry. Consequently, a novel series of 1,2,3-triazole – [1,2,4]triazolo[3,4-][1,3,4]thiadiazine hybrids ( &) were designed, synthesized, and screened for their anticancer activity against three human breast cancer cell lines, MCF-7, MDA-MB-231, and MDA-MB-415. Notably, hybrids and , featuring 4-fluorophenyl and 3,5-dichlorophenyl substitutions, respectively, exhibited superior activity against MCF-7 and MDA-MB-231 cell lines, and comparable activity against MDA-MB-415 cell line, compared to the standard drug Erlotinib. Toxicity studies on the noncancerous breast cell line MCF-10A indicate that these compounds are selective for cancer cell lines. Furthermore, these compounds demonstrated high efficacy in the EGFR inhibition assay, with IC values of 0.419 ± 0.05 μM and 0.312 ± 0.02 μM, respectively, in comparison to Erlotinib (IC: 0.421 ± 0.03 μM). experiments, including molecular docking studies to elucidate the interaction mode with the EGFR active site and ADMET analysis to verify drug-likeness properties, were also conducted for the potent compounds. Both experimental and investigations suggest that compounds and hold promise as lead compounds for further drug design and development endeavors.

中文翻译：

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1,2,3-三唑 – [1,2,4]三唑并[3,4-b][1,3,4]噻二嗪杂合体：改善靶向表皮生长因子受体的抗乳腺癌活性的开关


针对 EGFR 的抗癌药物的开发代表了药物化学领域的一个有前途的策略。因此，设计、合成并筛选了一系列新型 1,2,3-三唑 - [1,2,4]三唑并[3,4-][1,3,4]噻二嗪杂化物 (&)，以用于抗癌对三种人乳腺癌细胞系 MCF-7、MDA-MB-231 和 MDA-MB-415 具有活性。值得注意的是，与 4-氟苯基和 3,5-二氯苯基取代相比，杂种 和 分别对 MCF-7 和 MDA-MB-231 细胞系表现出优异的活性，并且对 MDA-MB-415 细胞系具有相当的活性。标准药物厄洛替尼。对非癌性乳腺细胞系 MCF-10A 的毒性研究表明，这些化合物对癌细胞系具有选择性。此外，这些化合物在 EGFR 抑制测定中表现出高效能，与厄洛替尼（IC50：0.421 ± 0.03 μM）相比，IC 值分别为 0.419 ± 0.05 μM 和 0.312 ± 0.02 μM。还对有效化合物进行了实验，包括阐明与 EGFR 活性位点相互作用模式的分子对接研究和验证药物相似性的 ADMET 分析。实验和研究都表明，这些化合物有望成为进一步药物设计和开发工作的先导化合物。