Design, synthesis and In Vitro evaluation on glucosamine-6P synthase of aromatic analogs of 2-Aminohexitols-6P

Abstract

A glicosamina-6-fosfato sintase (GlmS) catalisa a formação de glicosamina-6-fosfato a partir de frutose-6-fosfato. Esta é a primeira etapa da via biossintética de aminoaçúcares, componentes estruturais importantes da parede celular de fungos e bactérias. Este trabalho descreve o planejamento, a síntese e a avaliação da atividade inibitória da GlmS de dois novos compostos aromáticos enantioméricos, análogos de 2-amino-2-desoxi-D-glucitol-6-fosfato (ADGP) e de seu epímero 2-amino-2-desoxi-D-manitol-6-fosfato (ADMP), dois importantes inibidores da GlmS. Os análogos aromáticos apresentaram atividade inibitória modesta, na faixa de mmol L-1. The aminosugars are very important structural components of bacterial and fungi cell walls. Glucosamine-6-phosphate synthase (GlmS), which catalyses the first step of the aminosugar biosynthetic pathway i.e. the formation of D-glucosamine-6-phosphate from D-fructose-6phosphate, is therefore an interesting target in the fight against microorganisms. In this work is described the synthesis of aromatic analogs of 2-amino-2-deoxy-D-glucitol-6-phosphate (ADGP) and its epimer 2-amino-2-deoxy-D-manitol-6-phosphate (ADMP), two important inhibitors of GlmS. The aromatic analogs displayed modest inhibitory activity against GlmS, with IC 50 in the mmol L-1 range.

Synthesis of a novel series of 2,3,4-trisubstituted oxazolidines designed by isosteric replacement or rigidification of the structure and cytotoxic evaluation

“…Treatment of alcohol 15 with 4-nitrothiophenol under Mitsunobu conditions provided sulfur isostere in 31% yield. 32 The antiproliferative activity of compounds 1-7 was assessed on four human cancer cells lines, namely, HL60 promyelocytic leukemia, JURKAT T cell leukemia, MDA-MB-231 breast carcinoma cells and LNCaP prostate adenocarcinoma cells. Cytotoxic effects on normal cells were evaluated using VERO African green monkey kidney cells and PBMC peripheral blood mononuclear cells.…”

Efficient Synthesis and Anti-Fungal Activity of Oleanolic Acid Oxime Esters

“…Inhibitory activity of all the synthesized compounds towards Candida albicans GlcN-6-P synthase was evaluated using the further optimized Elson-Morgan method [25,26,27,29]. The absorption value of the solution was measured at 585 nm, and then the concentration was counted by the specification curve which was determined thanks to the relation between the absorption value and the concentration of glucosamine-6-phosphate.…”

Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate

“…Compounds 1 and 2 were prepared as described elsewhere (Dias et al, 2009). In the same vein, compounds 3 and 4 were prepared as follows.…”

“…The compounds 1 and 2, R and S tert-butyl 4-((3-hydroxyphenoxy) methyl)-2,2-dimethyloxazolidine-3-carboxylate -BHDC, were prepared as described elsewhere (Dias, et al, 2009). Using a similar strategy, compounds 3 and 4 (BNDC) were prepared, according to the synthetic route shown in Scheme 1.…”