Alhadhrami Nahlah A, Riyadh Sayed M, Ahmed Mohamed S M, Abdallah Zeinab A, Farghaly Thoraya A, Hussein Shadia M
Chemistry Department, Faculty of Science, Taibah University, Al-Madinah, Almunawrah 30002, Saudi Arabia.
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
ACS Omega. 2025 Aug 12;10(33):38164-38174. doi: 10.1021/acsomega.5c05914. eCollection 2025 Aug 26.
Hydrazono-[1,3,4]-thiadiazoles have a prominent position among the heterocyclic compounds due to their broadening aspects of biological activities. In the current study, a neoteric series of [1,3,4]-thiadiazoles tethered to alkoxyaryl hydrazone has been formulated via the treatment of methyl 2-[3-(pentyloxy)-benzylidene]-hydrazine-1-carbodithioate and hydrazonoyl chlorides in ethanolic solution under thermal conditions. DABCO, as an environmentally nontoxic material, was utilized as a superior basic catalyst for the latter reaction. The structures of the isolated products were explicated by spectral (IR, NMR, and MS) and elemental analysis tools. The antitumor activity of the synthesized products was assessed against the breast cancer MCF-7 cell line. The results displayed that compounds and have highly selective inhibition profiles related to doxorubicin as a reference drug. The molecular docking analysis was performed using the Molecular Operating Environment (MOE) software through the interaction with the VEGFR-2 protein (PDB: 2OH4) and revealed that compounds and are linked with the same amino acid (GLU883), similar to the reference antibiotic doxorubicin. Also, these compounds exhibited higher binding affinities (-7.86 and -8.47 kcal/mol, respectively) than the reference compound (-6.68 kcal/mol), which supported their antitumor efficacy against the MCF-7 cell line. Moreover, confirmation of the drug-like properties and toxicity predictions of the newly synthesized compounds (-) was achieved via in silico ADME.
腙基-[1,3,4]-噻二唑因其广泛的生物活性，在杂环化合物中占据显著地位。在本研究中，通过在热条件下于乙醇溶液中处理2-[3-(戊氧基)-亚苄基]-肼-1-碳二硫代酸甲酯和腙酰氯，制备了一系列与烷氧基芳基腙相连的新型[1,3,4]-噻二唑。作为环境无毒材料的1,4-二氮杂二环[2.2.2]辛烷（DABCO）被用作后一反应的优良碱性催化剂。通过光谱（红外、核磁共振和质谱）和元素分析工具对分离产物的结构进行了阐释。评估了合成产物对乳腺癌MCF-7细胞系的抗肿瘤活性。结果显示，化合物[具体化合物编号未给出]和[具体化合物编号未给出]具有与作为参考药物的阿霉素相关的高选择性抑制谱。使用分子操作环境（MOE）软件通过与血管内皮生长因子受体-2蛋白（PDB：2OH4）的相互作用进行了分子对接分析，结果表明化合物[具体化合物编号未给出]和[具体化合物编号未给出]与相同的氨基酸（GLU883）相连，类似于参考抗生素阿霉素。此外，这些化合物表现出比参考化合物（-6.68千卡/摩尔）更高的结合亲和力（分别为-7.86和-8.47千卡/摩尔），这支持了它们对MCF-7细胞系的抗肿瘤功效。此外，通过计算机辅助药物代谢动力学（ADME）实现了对新合成化合物[具体化合物编号未给出]的类药物性质和毒性预测的确认。
