Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, Poland.
Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, Instytucka 3, 05-110 Jabłonna, Poland.
Molecules. 2022 Oct 13;27(20):6865. doi: 10.3390/molecules27206865.
The impact of substituent at phenyl ring of diethyl benzylphosphonate derivatives on cytotoxic activity was studied. The organophosphonates were obtained based on developed palladium-catalyzed α, β-homodiarylation of vinyl esters protocol. The new synthetic pathway toward 1,2-bis(4-((diethoxyphosphoryl)methyl)phenyl)ethyl acetate was proposed which significantly improves the overall yield of the final product (from 1% to 38%). Several newly synthesized organophosphonates were tested as new potential antimicrobial drugs on model bacterial strains (K12 and R2-R3). All tested compounds show the highest selectivity and activity against K12 and R2 strains. Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that selected benzylphosphonate derivatives may have greater potential as antibacterial agents than typically used antibiotics such as ciprofloxacin, bleomycin and cloxacillin. These compounds are highly specific for pathogenic strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics, which is especially important due to the increasing resistance of bacteria to various drugs and antibiotics.
研究了二乙基苄基膦酸酯衍生物苯环取代基对细胞毒性活性的影响。这些有机膦酸酯是基于开发的钯催化的乙烯基酯的α，β-同二芳基化反应方案获得的。提出了一种新的合成 1,2-双（4-（（二乙氧基膦酰基）甲基）苯基）乙醋酸盐的新途径，该途径显著提高了最终产物的总收率（从 1%提高到 38%）。几种新合成的有机膦酸酯被用作新型潜在抗菌药物，对模型细菌菌株（K12 和 R2-R3）进行了测试。所有测试的化合物对 K12 和 R2 菌株表现出最高的选择性和活性。使用 MIC 和 MBC 测试和细菌 DNA 修饰后的 Fpg 消化进行的初步细胞研究表明，选择的苄基膦酸酯衍生物可能比通常使用的抗生素（如环丙沙星、博来霉素和氯唑西林）更有潜力作为抗菌剂。这些化合物基于使用的模型菌株对病原菌菌株具有高度特异性，将来可能作为常用抗生素的替代品，这在由于细菌对各种药物和抗生素的耐药性不断增加的情况下尤为重要。
