The Effects of N

Leishmaniasis is a disease that affects millions of people worldwide. The drugs that are available for the treatment of this infection exhibit high toxicity and various side effects. Several studies have focused on the development of new chemotherapeutic agents that are less toxic and more effective against trypanosomatids. We investigated the effects of N-butyl-1-(4-dimethylamino)phenyl-1,2,3,4-tetrahydro-β-carboline-3-carboxamide (C4) and its possible targets against L. amazonensis. The results showed morphological and ultrastructural alterations, depolarization of the mitochondrial membrane, the loss of cell membrane integrity, and an increase in the formation of mitochondrial superoxide anions in L. amazonensis treated with C4. Our results indicate that C4 is a selective antileishmanial agent, and its effects appear to be mediated by mitochondrial dysfunction

New 3-tetrazolyl-beta-carbolines and beta-carboline-3-carboxylates with anti-cancer activity

The synthesis and in vitro anticancer activity of novel beta-carbolines is reported. New tryptamines have been prepared via hetero-Diels-Alder reaction of nitrosoalkenes with indoles and used to prepare functionalized beta-carbolines by the Pictet-Spengler approach. These included 6-substituted-beta-carboline-3-carboxylates and 3-(1H-tetrazol-5-yl)-beta-carbolines, whose synthesis is reported for the first time. Carboline-3-carboxylates derived from L-tryptophan methyl ester were also prepared. The structural diversity that was achieved allowed the discovery of impressive activities against a range cancer cell lines with the selectivity depending on the type of substitution pattern of the beta-carboline core. We have identified at least one beta-carboline derivative with GI(50) < 1 mu M for each of the following human tumor cell lines: glioblastoma (U251), melanona (UACC-61), breast (MCF-7), ovarian expressing multiple-drug-resistance phenotype 4 (NCI-ADR/RES), renal (786-0), lung (NCI-H460), ovarian cancer (OVCAR-3), leukemia (K-562) and colon (HT29). These results demonstrated that the new 3-carboline derivatives are very promising anticancer agents179123132CNPQ - Conselho Nacional de Desenvolvimento Científico e Tecnológico201583/2014-