Banca de DEFESA: CAMILLA AMANDA DE OLIVEIRA GOMES

TECHNOLOGICAL PROSPECTION OF THE TREATMENT OF VISCERAL LEISHMANIASIS AND IN VITRO 

LEISHMANICIDAL POTENTIAL OF SYNTHETIC COMPOUNDS DERIVED FROM PURPUROGALINE

Technological prospecting; Leishmaniasis; Synthetic products; Purpurogallin derivatives.

Leishmaniasis is an endemic parasitic disease in approximately 102 countries and remains a serious public health problem. Currently, the available drugs have several pharmacotherapeutic limitations, and the search for new prototypes is urgent. In this context, a patent review of pharmacological innovations for the treatment of visceral leishmaniasis in the Americas over the last six years (2017-2023) was conducted. By inserting descriptors 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) patents were found for subsequent analysis of publication year parameters, IPC, country of origin, authors, pharmacological assays and bioactives. Eleven patents report leishmanicidal activity in the Leishmania infantum chagasi species in vitro and in vivo of synthetic or natural bioactives. Furthermore, this study aims to investigate the cytotoxic and leishmanicidal activity in vitro of synthetic derivatives of purpurogallin in the species Leishmania amazonensis and Leishmania infantum chagasi. 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 demonstrated low cytotoxicity in the J774.A1 lineage (macrophages) up to the highest tested concentration (100 μM) with a maximum effect <50%, except for 19a and 18e, which exhibited cytotoxicity >80%. Substances 19a, 18b, 18d and 18e were cytotoxic against promastigotes of both species, with a maximum effect >80%. It was found that derivative 18 showed significant selectivity against L. infantum chagasi strains with a selectivity index >10,06. Therefore, efficient pharmacological innovations were observed in inhibiting the parasite causing visceral leishmaniasis in the Americas, as well as the leishmanicidal activity of purpurogallin derivatives in both tested Leishmania species and low cytotoxicity against host cells.