Nosocomial infections are an important cause of morbi-mortality worldwide. The increase in the rate of resistance to conventional drugs in these microorganisms has stimulated the search for new therapeutic options. The nitro moiety (NO2) is an important pharmacophore of molecules with high anti-infective activity. We aimed to synthesize new nitro-derivates and to evaluate their antibacterial and anti-Candida potential in vitro. Five compounds [3-nitro-2-phenylchroman-4-ol (3); 3-nitro-2-phenyl-2H-chromene (4a); 3-nitro-2-(4-chlorophenyl)-2H-chromene (4b); 3-nitro-2-(4-fluorophenyl)-2H-chromene (4c), and 3-Nitro-2-(2,3-dichlorophenyl)-2H-chromene (4d)] were efficiently synthesized by Michael-aldol reaction of 2-hydroxybenzaldehyde with nitrostyrene, resulting in one β-nitro-alcohol (3) and four nitro-olefins (4a-4d). The antibacterial and anti-Candida potentials were evaluated by assaying minimal inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC). Mono-halogenated nitro-compounds (4b and 4c) showed anti-staphylococcal activity with MIC values of 15.6-62.5 μg/mL and MBC of 62.5 μg/mL. However, the activity against Gram-negative strains was showed to be considerably lower and our data suggests that this effect was associated with the outer membrane. Furthermore, nitro-compounds 4c and 4d presented activity against Candida spp. with MIC values ranging from 7.8-31.25 μg/mL and MFC of 15.6-500 μg/mL. In addition, these compounds were able to induce damage in fungal cells increasing the release of intracellular material, which was associated with actions on the cell wall independent of quantitative changes in chitin and β-glucan. Together, these findings show that nitro-compounds can be exploited as anti-staphylococcal and anti-Candida prototypes.

中文翻译：

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新的硝基化合物作为针对医院病原体的抗菌剂的药理潜力：设计，合成和体外有效性。

医院感染是世界范围内致死率的重要原因。这些微生物对常规药物的耐药率增加，促使人们寻求新的治疗选择。硝基部分（NO2）是具有高抗感染活性的分子的重要药效团。我们旨在合成新的硝基衍生物，并在体外评估其抗菌和抗念珠菌的潜力。五种化合物[3-硝基-2-苯基苯并吡喃-4-醇（3）; 3-硝基-2-苯基-2H-亚甲基（4a）; 3-硝基-2-（4-氯苯基）-2H-亚甲基（4b）; 3-硝基-2-（4-氟苯基）-2H-色烯（4c）和3-硝基-2-（2,3-二氯苯基）-2H-色烯（4d）]是由2-羟基苯甲醛与硝基苯乙烯，生成一种β-硝基醇（3）和四种硝基烯烃（4a-4d）。通过测定最小抑菌浓度（MIC），最小杀真菌浓度（MFC）和最小杀菌浓度（MBC）来评估抗菌和抗念珠菌的潜力。单卤化硝基化合物（4b和4c）显示抗葡萄球菌活性，MIC值为15.6-62.5μg/ mL，MBC为62.5μg/ mL。然而，对革兰氏阴性菌株的活性显示相当低，我们的数据表明这种作用与外膜有关。此外，硝基化合物4c和4d表现出针对念珠菌的活性。MIC值为7.8-31.25μg/ mL，MFC值为15.6-500μg/ mL。此外，这些化合物能够诱导真菌细胞中的损伤，从而增加细胞内物质的释放，其与细胞壁上的作用无关，而与几丁质和β-葡聚糖的定量变化无关。总之，这些发现表明，硝基化合物可以用作抗葡萄球菌和抗念珠菌的原型。