Singh Anju, Beg Mirza Adil, Jamal Samra, Khan Arif, Rahman Abdur, Selvapandiyan Angamuthu, Shafi Syed, Hoda Nasimul
Department of Chemistry, Drug Design and Synthesis Lab., Jamia Millia Islamia Jamia Nagar New Delhi 110025 India
Department of Molecular Medicine, Jamia Hamdard New Delhi 110062 India.
RSC Adv. 2024 Jul 17;14(31):22587-22597. doi: 10.1039/d4ra01904k. eCollection 2024 Jul 12.
Amongst the neglected tropical diseases, leishmaniasis alone causes 30 000 deaths annually due to the protozoan parasite genus . Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost. Therefore, new safer and shorter treatments are an urgent need of the time. Herein, we report the synthesis of fifteen novel diphenyl triazine and diphenyl triazine pyrimidine derivatives and their antileishmanial properties against , that causes fatal visceral leishmaniasis. Most of the synthesized analogues exhibited more than 90% inhibition against the promastigote stage of the parasite. Moreover, compounds T4 and T7 showed potent activity against extracellular promastigote (IC = 1.074 μM and IC = 1.158 μM) as compared to miltefosine (IC = 1.477 μM) and is nontoxic towards the host THP-1 macrophage cell line. Interestingly, compound T4 exhibited significant activity against amastigotes (7.186 μM) and induced the macrophages to prevent the survival of the parasite. Our results indicate that T4 represents a new structural lead for this serious and neglected disease.
在被忽视的热带疾病中，仅利什曼病每年就因原生动物寄生虫属导致3万例死亡。现有疗法在安全性、耐药性、现场适应性应用和成本方面存在严重缺陷。因此，新的更安全、更短疗程的治疗方法是当下的迫切需求。在此，我们报告了十五种新型二苯基三嗪和二苯基三嗪嘧啶衍生物的合成及其对导致致命内脏利什曼病的杜氏利什曼原虫的抗利什曼活性。大多数合成类似物对寄生虫的前鞭毛体阶段表现出超过90%的抑制作用。此外，与米替福新（IC = 1.477 μM）相比，化合物T4和T7对细胞外前鞭毛体显示出强效活性（IC = 1.074 μM和IC = 1.158 μM），并且对宿主THP-1巨噬细胞系无毒。有趣的是，化合物T4对无鞭毛体表现出显著活性（7.186 μM），并诱导巨噬细胞阻止寄生虫存活。我们的结果表明，T4代表了这种严重且被忽视疾病的一种新的结构先导物。
