RESUMO
The discovery and development of antimicrobial agents that do not give rise to resistance remains an ongoing challenge. Our efforts in this regard continue to reveal new potential therapeutic agents with differing physicochemical properties while retaining the effective N,N-dichloroamine pharmacophore as the key antimicrobial warhead. In this Letter, we disclose agents containing polyol units as a water solubilizing group. These sulfonyl-polyol agents show broad spectrum bactericidal and virucidal activity. These compounds show 1 h MBC's of 16-512 µg/mL against Escherichia coli and 4-256 µg/mL against Staphylococcus aureus at neutral pH, and 1-h IC50's of 4.5-32 µM against Adenovirus 5 and 0.7-3.0 µM against Herpes simplex virus 1. The lead compounds were tested in a tissue culture irritancy assay and showed only minimal irritation at the highest concentrations tested.
Assuntos
Aminas/química , Anti-Infecciosos/química , Polímeros/química , Adenoviridae/metabolismo , Aminas/síntese química , Aminas/farmacologia , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Efeito Citopatogênico Viral/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Herpesvirus Humano 1/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Células VeroRESUMO
Antimicrobial compounds with broad-spectrum activity and minimal potential for antibiotic resistance are urgently needed. Toward this end, we prepared and investigated a novel series of N-chloroheterocycles. Of the compounds examined, the N-chloroamine series were found superior over N-chloroamide series in regards to exhibiting high antimicrobial activity, low cytotoxicity, and long-term aqueous stability.
Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Anti-Infecciosos/síntese química , Cloro/química , Compostos Heterocíclicos/síntese química , Testes de Sensibilidade Microbiana , Estrutura MolecularRESUMO
Antimicrobial resistance against many known therapeutics is on the rise. We examined derivatives of 3-chlorooxazolidin-2-one 1a (X=H) as antibacterial and antifungal agents. The key findings were that the activity and apparent in vitro cytotoxicity could be controlled by the substitution of charged solubilizers at the 4- and 5- positions. These changes both significantly increase the antifungal potency and decrease cytotoxicity. Particularly effective were trialkylammonium groups which led to 400- to 600-fold increases in the antifungal therapeutic index when compared to their unsubstituted counterparts.