RESUMO
A group of 28 N-benzylidene aniline derivatives structurally related to the natural stilbene resveratrol has been prepared through condensation of anilines with the corresponding aldehydes. The ability of these imines to inhibit proliferation of two tumor cell lines (HT-29 and MCF-7) and one non-tumor cell line (HEK- 293) was first determined. Subsequently, we determined the ability of some of the most cytotoxic compounds to inhibit the secretion of the VEGF-A factor in HT-29 cells and to downregulate the expression of the VEGF and hTERT genes, the latter one being involved in the activation of telomerase.
Assuntos
Iminas/síntese química , Iminas/farmacologia , Resveratrol/farmacologia , Telomerase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Estrutura Molecular , Resveratrol/química , Telomerase/genética , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7-9 and 17, were active against Leishmania parasites (EC50=9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25-27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.
Assuntos
Antiprotozoários/farmacologia , Chalconas/farmacologia , Cumarínicos/farmacologia , Leishmania/efeitos dos fármacos , Triclosan/análogos & derivados , Triclosan/farmacologia , Antiprotozoários/síntese química , Linhagem Celular Tumoral , Chalconas/síntese química , Cumarínicos/síntese química , Avaliação Pré-Clínica de Medicamentos , Humanos , Concentração Inibidora 50 , Leishmaniose/tratamento farmacológico , Triclosan/síntese químicaRESUMO
Stereoselective syntheses of five naturally occurring, pharmacologically active medium and large ring lactones are described. Key synthetic methods used were, depending on the cases, olefin metatheses, asymmetric allylations and C-glycosidations.
Assuntos
Alcanos/síntese química , Alcenos/síntese química , Compostos Heterocíclicos com 1 Anel/síntese química , Cetonas/síntese química , Macrolídeos/síntese química , EstereoisomerismoRESUMO
The delta-lactone boronolide (+)-1, a pharmacologically active, naturally occurring product, has been synthesized in enantiopure form with L-erythrulose as the chiral starting material. The key steps of the synthesis were a highly stereoselective aldol-reduction one-pot sequence, an indium-mediated diastereoselective aldehyde allylation, and a ring-closing metathesis.