Prospecção tecnológica do tratamento de leishmaniose visceral e potencial leishmanicida in vitro dos compostos sintéticos derivados da purpurogalina

Abstract

Leishmaniasis is an endemic parasitic disease in approximately 102 countries and continues to be a serious public health problem. Currently, the available drugs have everal pharmacotherapeutic limitations, and the search for new prototypes is urgent. In this context, the study aims to conduct a patent review of pharmacological innovations for the treatment of visceral leishmaniasis in the Americas over the past six years (2017- 2023), as well as to investigate the cytotoxic and leishmanicidal activity in vitro of synthetic derivatives of purpurogallin in L. amazonensis and L. infantum chagasi species. In the patent review, the descriptors were inserted into platforms such as The Lens, World Intellectual Property Organization (WIPO), European Patent Office (EPO), United States Patent and Trademark Office (USPTO) and Brazilian Patent and Trademark Office (INPI), finding patents for subsequent analysis of publication year parameters, IPC, country of origin, authors, pharmacological assays, and bioactive assays. In the experimental study, the MTT colorimetric assay (3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide) was performed to determine the cytotoxicity of the derivatives in macrophages, followed by anti-Leishmania evaluation in promastigotes of the mentioned species and determination of the selectivity index. The results obtained showed eleven patents describing synthetic and natural pharmacological innovations against L. infantum chagasi in vitro and in vivo over the last seven years. Regarding the experimental assays, low cytotoxicity was observed in the J774.A1 lineage (macrophages) up to the highest tested concentration (100 pM), with a maximum effect of less than 50%, except for compounds 19a and 18e, which had cytotoxicity greater than 80%. Substances 19a, 18b, 18d, and 18e were cytotoxic against promastigotes of both species, with a maximum effect greater than 80%. It was found that derivative 18 demonstrated significant selectivity against strains of L. infantum chagasi with a selectivity index greater than 10,06. Therefore, patent studies indicate pharmacological innovations with leishmanicidal activity against the causative agent of visceral leishmaniasis in the Americas, as well as the potential anti-Leishmania of purpurogallin derivatives in both tested species of Leishmania and low cytotoxicity against host cells.