IN VITRO LEISHMANICIDAL POTENTIAL OF SYNTHETIC COMPOUNDS DERIVED FROM PURPUROGALINE
Leishmaniasis; Synthetic products; Purpurogallin derivatives.
Leishmaniasis is an endemic parasitic disease in approximately 102 countries and continues to be a serious public health problem. Currently, the available drugs have several pharmacotherapeutic limitations, so the search for new prototypes is essential. 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 entering the chosen descriptors into The Lens, WIPO, EPO, USPTO and INPI platforms, patents were found and subsequently analyzed based on parameters such as year of publication, IPC, country of origin, authors, pharmacological and bioactive assays. After this investigation, 9 documents remained that describe the leishmanicidal activity against the species L. infantum chagasi in vitro and in vivo of synthetic or natural bioactives. Furthermore, this study aims to investigate the in vitro cytotoxic and leishmanicidal activity of synthetic derivatives of purpurogalin against the species L. amazonensis and L. infantum chagasi. In the experimental study, MTT reduction assays were performed to determine cytotoxicity in macrophages, followed by the evaluation of anti-Leishmania activity of synthetic derivatives on promastigotes of the mentioned species and the determination of the selectivity index. The results obtained showed low cytotoxicity in the J774.A1 cell line (macrophages) up to the highest tested concentration (100 μM), with a maximum effect <50%, except for IAS 5 and 8, which had cytotoxicity >80%. Compounds IAS 5, 6, 7, and 8 were cytotoxic against promastigotes of both species, with a maximum effect >80%. It was observed that IAS 2 demonstrated significant selectivity against L. infantum chagasi strains with an index of >10,06. Therefore, efficient pharmacological innovations in inhibiting the parasite responsible for visceral leishmaniasis in the Americas were observed, as well as leishmanicidal activity of purpurogalin derivatives in both tested Leishmania species and low cytotoxicity against host cells (macrophages).