Costa Natalia C S, Dos Anjos Luana Ribeiro, de Souza João Victor Marcelino, Brasil Maria Carolina Oliveira de Arruda, Moreira Vitor Partite, Graminha Marcia A S, Lubec Gert, Gonzalez Eduardo Rene P, Cilli Eduardo Maffud
Department of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), 14800-060 Araraquara, São Paulo, Brazil.
Fine Organic Chemistry Lab, School of Sciences and Technology, São Paulo State University (UNESP), 19060-080 Presidente Prudente, Sao Paulo, Brazil.
ACS Omega. 2023 Sep 6;8(37):34008-34016. doi: 10.1021/acsomega.3c04878. eCollection 2023 Sep 19.
Leishmaniasis refers to a collection of diseases caused by protozoa from the genus. These diseases, along with other parasitic afflictions, pose a significant public health issue, particularly given the escalating number of at-risk patients. This group includes immunocompromised individuals and those residing in impoverished conditions. The treatment of leishmaniasis is crucial, particularly in light of the mortality rate associated with nontreatment, which stands at 20-30,000 deaths per year globally. However, the therapeutic options currently available are limited, often ineffective, and potentially toxic. Consequently, the pursuit of new therapeutic alternatives is warranted. This study aims to design, synthesize, and evaluate the leishmanicidal activity of antimicrobial peptides functionalized with guanidine compounds and identify those with enhanced potency and selectivity against the parasite. Accordingly, three bioconjugates were obtained by using the solid-phase peptide synthesis protocol. Each proved to be more potent against intracellular amastigotes than their respective peptide or guanidine compounds alone and demonstrated higher selectivity to the parasites than to the host cells. Thus, the conjugation strategy employed with these compounds effectively contributes to the development of new molecules with leishmanicidal activity.
利什曼病指的是由利什曼原虫属原生动物引起的一系列疾病。这些疾病与其他寄生虫病一起，构成了一个重大的公共卫生问题，尤其是考虑到高危患者数量不断增加。这一群体包括免疫功能低下者和生活在贫困条件下的人。利什曼病的治疗至关重要，特别是鉴于不治疗的死亡率，全球每年有2万至3万人死亡。然而，目前可用的治疗选择有限，往往无效且可能有毒。因此，有必要寻求新的治疗方法。本研究旨在设计、合成并评估用胍化合物功能化的抗菌肽的杀利什曼原虫活性，并鉴定出对该寄生虫具有增强效力和选择性的抗菌肽。据此，通过固相肽合成方案获得了三种生物共轭物。每种生物共轭物对细胞内无鞭毛体的活性均比其各自的肽或胍化合物单独使用时更强，并且对寄生虫的选择性高于对宿主细胞的选择性。因此，与这些化合物采用的共轭策略有效地促进了具有杀利什曼原虫活性的新分子的开发。
