Centre of Excellence for Pharmaceutical Sciences (Pharmacen), Faculty of Health Sciences, North-West University, 11 Hoffmann Street, Potchefstroom, 2520, South Africa.
School of Pharmacy, Faculty of Health Sciences, North-West University, 11 Hoffmann Street, Potchefstroom, 2520, South Africa.
ChemMedChem. 2022 May 18;17(10):e202200023. doi: 10.1002/cmdc.202200023. Epub 2022 May 2.
Leishmaniasis is a vector-borne neglected parasitic infection affecting thousands of individuals, mostly among populations in low- to moderate-income developing countries. In the absence of protective vaccines, the management of the disease banks solely on chemotherapy. However, the clinical usefulness of current antileishmanial drugs is threatened by their toxicity and the emergence of multidrug-resistant strains of the causative pathogens. This emphasizes the imperative for the development of new and effective antileishmanial agents. In this regard, we synthesized and evaluated in vitro the antileishmanial activity and cytotoxicity profile of a series of nitrofurantoin-triazole hybrids. The nitrofurantoin derivative 1 featuring propargyl moiety was distinctively the most active of all, was nontoxic to human cells and possessed submicromolar cellular activity selectively directed towards the pathogens of the life threatening visceral leishmaniasis. Hence it was identified as potential antileishmanial lead for further investigation into its prospective to act as alternative to therapies.
利什曼病是一种由媒介传播的被忽视的寄生虫感染，影响着成千上万的人，主要发生在中低收入发展中国家的人群中。在缺乏保护性疫苗的情况下，该病的治疗完全依赖于化疗。然而，由于现有抗利什曼病药物的毒性和病原体多药耐药株的出现，其临床应用受到了威胁。这强调了开发新的有效抗利什曼病药物的必要性。在这方面，我们合成并评估了一系列硝基呋喃妥因-三唑杂合体的抗利什曼病活性和细胞毒性特征。带有炔丙基部分的硝基呋喃妥因衍生物 1 是所有化合物中最具活性的，对人细胞无毒，并且具有亚微摩尔级的细胞活性，选择性地针对危及生命的内脏利什曼病的病原体。因此，它被确定为具有进一步研究潜力的潜在抗利什曼病先导化合物，有望替代现有疗法。
