Design and Synthesis of Sulfanilamide Aminophosphonates as Novel Antibacterial Agents towards Escherichia coli

Abstract

The limit ability of traditional antibiotics to treat drug resistant bacteria calls for new therapeutic alternatives. A class of unique sulfanilamide aminophosphonates as new potential agents against microbes was synthesized by one-pot three-component reaction. Noticeably, fluorobenzyl derivative 5d (MIC = 2 μg/mL) was active against drug resistant E. coli infection and exerted no obvious toxicity towards human mammalian cells. Compound 5d also displayed good anti-biofilm activity and low possibility to induce drug resistance. Mechanism investigation elucidated that molecule 5d could disrupt E. coli membrane through generation of reactive oxygen (ROS) and then intercalate into deoxyribonucleic acid (DNA) to form a steady 5d-DNA complex, which led to bacterial death. These results indicated that sulfanilamide aminophosphonates would shed light on developing novel potential antibacterial agents.

Unique Carbazole-Oxadiazole Derivatives as New Potential Antibiotics for Combating Gram-Positive and -Negative Bacteria

“…Human blood hemolysis assay was conducted according to the previously published methods with slight modifications. , Fresh blood (10 mL) was centrifuged at 4000 rpm for 10 min, and the supernatant was discarded. The RBCs were laved three times with physiological saline until the supernatant did not show red.…”

Natural Berberine-derived Azolyl Ethanols as New Structural Antibacterial Agents against Drug-Resistant Escherichia coli

“…Alcohol is often used for disinfection and sterilization in daily life that can penetrate the surface of the membrane and denature the protein. , Particularly, amino alcohols have proved to possess significant antibacterial capacity . Azoles as crucial members in the antimicrobial arsenal have achieved considerable success in the treatment of infectious diseases and remain relatively low in resistant incidents. , Structurally simple metronidazole as the assembly of nitroimidazole and ethanol displays potent activity against obligate anaerobes in the clinic, and this prominent success has stimulated continuous efforts to develop diverse clinical hydroxyethyl azoles such as secnidazole, ornidazole, fluconazole, and voriconazole in treating pathogenic infections . To combat drug-resistance infections, recent numerous researches strived to incorporate hydroxyethyl azoles with antibacterial skeletons like sulfanilamide, quinolone, and coumarin for discovering new antimicrobials, some of which effectively hinder the vital biological functions of bacteria. − Therefore, the hybridization of hydroxyethyl azole fragments with berberine might be a promising strategy to construct new antibacterial molecules with potentially good bioavailability and favorable bioactivity.…”

“…17 Azoles as crucial members in the antimicrobial arsenal have achieved considerable success in the treatment of infectious diseases and remain relatively low in resistant incidents. 18,19 Structurally simple metronidazole as the assembly of nitroimidazole and ethanol displays potent activity against obligate anaerobes in the clinic, 20 and this prominent success has stimulated continuous efforts to develop diverse clinical hydroxyethyl azoles such as secnidazole, ornidazole, fluconazole, and voriconazole in treating pathogenic infections. 21 To combat drug-resistance infections, recent numerous researches strived to incorporate hydroxyethyl azoles with antibacterial skeletons like sulfanilamide, quinolone, and coumarin for discovering new antimicrobials, some of which effectively hinder the vital biological functions of bacteria.…”

Natural Berberine-Hybridized Benzimidazoles as Novel Unique Bactericides against Staphylococcus aureus

“…The successful applications of antibacterial azoles greatly hindered the invasion of bacteria in humans, terrestrial and aquatic animals, as well as plants. − In particular, benzimidazoles have attracted considerable attention because of the purine-like structure in benzimidazole ring that enabled benzimidazole derivatives to block the biosynthesis of proteins and nucleic acids. , A variety of bactericides containing benzimidazole fragment have been launched into the market, such as carbendazim and thiabendazole, demonstrating the enormous potentiality in the antibacterial aspect.…”