Infectious Disease Laboratory, Campus Ministro Reis Velloso, Federal University of Parnaíba Delta, 64202-020 Parnaíba, PI, Brasil.
Microscopy and Microanalysis Laboratory, Department of Cell Biology, Institute of Biological Sciences, University of Brasília, Brasília, Brazil.
Int Immunopharmacol. 2023 Oct;123:110750. doi: 10.1016/j.intimp.2023.110750. Epub 2023 Aug 1.
Leishmaniasis, presenting the highest number of cases worldwide is one of the most serious Neglected Tropical Diseases (NTDs). Clinical manifestations are intrinsically related to the host's immune response making immunomodulatory substances the target of numerous studies on antileishmanial activity. The currently available drugs used for treatment present various problems including high toxicity, low efficacy, and associated drug resistance. The search for therapeutic alternatives is urgent, and in this context, thiophene derivatives appear to be a promising therapeutic alternative (many have shown promising anti-leishmanial activity). The objective of this study was to investigate the antileishmanial activity of the 2-amino-thiophenic derivative SB-200. The thiophenic derivative was effective in inhibiting the growth of Leishmania braziliensis, Leishmania major, and Leishmania infantum promastigotes, obtaining respective IC values of 4.25 μM, 4.65 μM, and 3.96 μM. For L. infantum, it was demonstrated that the antipromastigote effect of SB-200 is associated with cell membrane integrity losses, and with morphological changes observed during scanning and transmission electron microscopy. Cytotoxicity was performed for J774.A1 macrophages and VERO cells, to obtain a CC of 42.52 μM and a SI of 10.74 for macrophages and a CC of 39.2 μM and an SI of 9.89 for VERO cells. The anti-amastigote activity of SB-200 revealed an IC of 2.85 μM and an SI of 14.97 against macrophages and SI of 13.8 for VERO cells. The anti-amastigote activity of SB-200 is associated with in vitro immunomodulation. For acute toxicity, SB-200 against Zophobas morio larvae permitted 100% survival. We conclude that the 2-amino-thiophenic derivative SB-200 is a promising candidate for in vivo anti-leishmania drug tests to evaluate its activity, efficacy, and safety.
利什曼病是全球病例数最多的疾病之一，也是最严重的被忽视热带病之一。临床表现与宿主的免疫反应密切相关，这使得免疫调节物质成为抗利什曼活性的众多研究的目标。目前用于治疗的药物存在各种问题，包括毒性高、疗效低和耐药性相关。寻找治疗替代方法迫在眉睫，在这种情况下，噻吩衍生物似乎是一种很有前途的治疗选择（许多噻吩衍生物已显示出有希望的抗利什曼活性）。本研究旨在研究 2-氨基噻吩衍生物 SB-200 的抗利什曼活性。噻吩衍生物有效抑制巴西利什曼原虫、大滋养体和婴儿利什曼原虫前鞭毛体的生长，获得相应的 IC 值分别为 4.25 μM、4.65 μM 和 3.96 μM。对于婴儿利什曼原虫，证明 SB-200 的抗前鞭毛体作用与细胞膜完整性的丧失以及扫描和透射电子显微镜观察到的形态变化有关。对 J774.A1 巨噬细胞和 VERO 细胞进行细胞毒性试验，获得巨噬细胞的 CC 为 42.52 μM 和 SI 为 10.74，以及 VERO 细胞的 CC 为 39.2 μM 和 SI 为 9.89。SB-200 的抗无鞭毛体活性显示对巨噬细胞的 IC 为 2.85 μM 和 SI 为 14.97，对 VERO 细胞的 SI 为 13.8。SB-200 的抗无鞭毛体活性与体外免疫调节有关。急性毒性试验中，SB-200 对黄粉虫幼虫的致死率为 100%。我们得出结论，2-氨基噻吩衍生物 SB-200 是一种很有前途的体内抗利什曼药物候选物，可用于评估其活性、疗效和安全性。
