Synthesis of 3-aryl-4-(N-aryl)aminocoumarins via photoredox arylation and the evaluation of their biological activity.

A new series of 3-aryl-4-(N-aryl)aminocoumarins was synthesized in two steps starting from the natural product 4-hydroxycoumarin using the photoredox catalysis for the key step. These conditions reactions allowed to make CC bonds is up to 95% yields in mild conditions, easy operation, in an environmentally benign way, and are compatible with several patterns of substitution. The biological activity of the new compounds was tested in vitro against MCF-7, MDA-MB-231, and CCD-1072Sk cancer cell lines, as soon as to promastigotes and intracellular amastigotes of Leishmania amazonensis. Compounds 17d, 17s and 17x showed activity against promastigote forms (IC50 = 5.96 ± 3.210, 9.05 ± 2.855 and 5.65 ± 2.078 µM respectively), and compound 17x presented the best activity against L. amazonensis amastigote intracellular form (IC50 = 9.6 ± 1.148 µM), no BALB/c peritoneal macrophage cytotoxicity at assayed concentrations (CC50 > 600 µM), and high selectivity to parasites over the mammalian cells (Selectivity Index > 62.2). There was no expressive activity for the cancer cell lines. Single crystal X-ray diffraction analysis was employed for structural elucidation of compounds 17a and 17s. In silico analyses of physicochemical, pharmacokinetic, and toxicological properties suggest that compound 17x is a potential candidate for anti-leishmaniasis drugs.

[Seroprevalence, clinical and biochemical data of dogs naturally infected by Leishmania and phlebotominae sandfly fauna in an endemic area in São Luis Island, Maranhão State, Brazil]. / Soroprevalência, aspectos clínicos e bioquímicos da infecção por Leishmania em cães naturalmente infectados e fauna de flebotomíneos em uma área endêmica na Ilha de São Luís, Maranhão, Brasil.

The aim of this study was to determine the seroprevalence, clinical and biochemical profile of Leishmania chagasi infection in dogs naturally infected and identify the phlebotominae fauna in an endemic area of São Luis Island. In this present study, 62 household mongrel dogs were sampled for antibodies anti-Leishmania. The seroprevalence was 51.61%. In the clinical evaluation, 36.68% dogs were symptomatic, 38.41% were oligosymptomatic and 26.13% were asymptomatic. The most frequent signs were onychogryphosis and lymphadenomegaly. In 29.41% animals were observed anemia. In the biochemical analysis hepatic function showed changes in relation to alaninoaminotransferase (ALT) and aspartato aminotransferase (AST). Urea values were higher than the references ones for canine specie. The following phlebotominae sandflies were identified: Lutzomyia longipalpis (86.9%), L. evandroi (9.6%), L. choti (2.1%), L. umbratilis (0.7%) e L. whitmani (0.7%).