Design,synthesis and biological evaluation of amino organophosphorus imidazoles as a new type of potential antimicrobial agents

A series of amino organophosphorus imidazoles were designed and synthesized as a novel structural type of antimicrobial agents.Bioactive evaluation in vitro showed that compound 3f exhibited equipotent or superior anti-methicillin-resistant Staphylococcus aureus(anti-MRSA) and anti-S. cerevisiae efficiencies(minimal inhibitory concentration(MIC)=2 μg/mL) to clinical drugs,and the combinations with antibacterial or antifungal drugs enhanced the antimicrobial efficiency. Highly active molecule 3f showed low propensity for bacteria to develop resistance, and the preliminary action mechanism studies demonstrated that 3f was membrane-active, but had no significant intercalation towards MRSA DNA. The computational study on 3f reasonably explained its high antimicrobial activity. Experimental data revealed that ground-state 3f-HSA complexes were formed mainly through hydrophobic interactions and hydrogen bonds with a spontaneous process, and the non-radioactive energy transfer from HSA to 3f occurred beyond F鰎ster resonance energy transfer theory. The participation of metal ions in 3f-HSA supramolucular system could increase the concentration of free compound 3f, and shorten its storage time and half-life in the blood to improve the maximum antimicrobial efficacy.

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

The limit ability of traditional antibiotics to treat drug resistant bacteria calls for new therapeutic alter natives.A class of unique sul-fanilamide aminophosphonates as new potential agents against microbes was synthesized by one-pot three-component reaction.

A New Discovery towards Novel Skeleton of Benzimidazole-Conjugated Pyrimidinones as Unique Effective Antibacterial Agents

A class of new potential antibacterial agents with distinctive pyrimidinone benzimidazole skeleton was developed through nucleophilic substitution and Biginelli reaction starting from urea,ethyl 4-chloroacetoacetate and various aldehydes.Some target molecules exhibited strong antibacterial activities,especially pyrimidinone benzimidazole hybrid 9e possessed the strongest inhibitory effects on the growth of E.faecalis and P.aeruginosa with a lower MIC value of 1μg/mL than norfloxacin.Moreover,compound 9e displayed strong antibiofilm capacity,low drug resistance and excellent biosafety toward human red blood cells.Further research revealed that compound 9e could disrupt membrane integrity and cause leakage of cellular components such as proteins and nucleic acids.Meanwhile,compound 9e could decrease lactate dehydrogenase activity,block cell metabolism and interact with DNA in an intercalation manner.

Novel potentially antibacterial naphthalimide-derived metronidazoles:Design,synthesis,biological evaluation and supramolecular interactions with DNA,human serum albumin and topoisomeraseⅡ

A series of novel naphthalimide-derived metronidazoles as new type of antimicrobial agents were for the first time designed, synthesized and characterized by NMR, IR and HRMS spectra. Experimental results revealed that most of them displayed moderate to good antibacterial activity towards Gram-positive and negative bacteria. Especially, compound 7b was able to not only exhibit effective inhibition towards the growth of P. vulgaris(MIC = 0.002 mmol/m L) and S. dysenteriae(MIC = 0.01 mmol/m L), but also have rapidly killing effect and prevent the development of bacterial resistance. Further research revealed that the highly active molecule 7b could not only intercalate into calf thymus DNA to form a steady supramolecular complex and thus might block DNA replication to exert the powerful bioactivities, but also be effectively transported by human serum albumin(HSA) via the formation of the 1:1supramolecular complex, in which hydrogen bonds and hydrophobic effect played important roles in the association of compound 7b with HSA. Molecular docking indicated that the supramolecular interactions between 7b and topoisomerase II were driven by hydrogen bonds.