Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia.
Molecules. 2022 Mar 30;27(7):2246. doi: 10.3390/molecules27072246.
Nitrogen-containing atoms in their core structures have been exclusive building blocks in drug discovery and development. One of the most significant and well-known heterocycles is the 1,3,4-thidiazole nucleus, which is found in a wide range of natural products and therapeutic agents. In the present work, certain -1,3,4-thiadiazole derivatives (, ) were synthesized through a multi-step synthesis approach. All synthesized compounds were characterized using different spectroscopic tools. Previously, thiadiazole compounds as anti- agents have been conducted and reported in vitro. However, this is the first study to test the anti- activity of manufactured molecular hybrids thiadiazole in an infected mouse model with the acute RH strain of . All the observed results demonstrated compound ()'s powerful activity, with a considerable reduction in the parasite count reaching 82.6% in brain tissues, followed by liver and spleen tissues (65.35 and 64.81%, respectively). Inflammatory and anti-inflammatory cytokines assessments proved that Compound 7 possesses potent antiparasitic effect. Furthermore, docking tests against CDPK1 and ROP18 kinase (two major enzymes involved in parasite invasion and egression) demonstrated compound 's higher potency compared to compound and megazol. According to the mentioned results, -1,3,4-thiadiazole derivatives under test can be employed as potent antiparasitic agents against the acute RH strain of .
含氮原子的核心结构一直是药物发现和开发的独特构建模块。最显著和著名的杂环之一是 1,3,4-噻二唑核,它存在于广泛的天然产物和治疗剂中。在本工作中,通过多步合成方法合成了某些 -1,3,4-噻二唑衍生物(, )。所有合成的化合物均使用不同的光谱工具进行了表征。先前,噻二唑类化合物作为抗疟药物已在体外进行了研究和报道。然而,这是首次在感染急性 RH 株的小鼠模型中测试制造的分子杂合噻二唑的抗疟活性。所有观察到的结果表明化合物()具有强大的活性,寄生虫数量减少了 82.6%,在脑组织中,其次是肝组织和脾组织(分别为 65.35%和 64.81%)。炎症和抗炎细胞因子评估证明,化合物 7 具有很强的抗寄生虫作用。此外,针对 CDPK1 和 ROP18 激酶(两种主要参与寄生虫入侵和逸出的酶)的对接测试表明,与化合物和甲硝唑相比,化合物具有更高的活性。根据所述结果,测试的 -1,3,4-噻二唑衍生物可用作针对急性 RH 株的有效抗疟药物。