23767-69-3Relevant academic research and scientific papers
Discovery of Potent Inhibitors of Streptococcus mutans Biofilm with Antivirulence Activity
Nijampatnam, Bhavitavya,Ahirwar, Parmanand,Pukkanasut, Piyasuda,Womack, Holly,Casals, Luke,Zhang, Hua,Cai, Xia,Michalek, Suzanne M.,Wu, Hui,Velu, Sadanandan E.
supporting information, p. 48 - 55 (2020/12/21)
Dental caries is a bacterial infectious disease characterized by demineralization of the tooth enamel. Treatment of this disease with conventional antibiotics is largely ineffective as the cariogenic bacteria form tenacious biofilms that are resistant to such treatments. The main etiological agent for dental caries is the bacterium Streptococcus mutans. S. mutans readily forms biofilms on the tooth surface and rapidly produces lactic acid from dietary sucrose. Glucosyl transferases (Gtfs) secreted by S. mutans are mainly responsible for the production of exopolysaccharides that are crucial for the biofilm architecture. Thus, inhibiting S. mutans' Gtfs is an effective approach to develop selective biofilm inhibitors that do not affect the growth of oral commensals. Herein, we report a library of 90 analogs of the previously identified lead compound, G43, and exploration of its structure activity relationships (SAR). All compounds were evaluated for the inhibition of S. mutans biofilms and bacterial growth. Selected compounds from this library were further evaluated for enzyme inhibition against Gtfs using a zymogram assay and for growth inhibition against oral commensal bacterial species such as Streptococcus gordonii and Streptococcus sanguinis. This study has led to the discovery of several new biofilm inhibitors with enhanced potency and selectivity. One of the leads, IIIF1, showed marked reduction in buccal, sulcal, and proximal caries scores in a rat model of dental caries.
Amide isosteres in structure-activity studies of antibacterial minor groove binders
Khalaf, Abedawn I.,Anthony, Nahoum,Breen, David,Donoghue, Gavin,MacKay, Simon P.,Scott, Fraser J.,Suckling, Colin J.
experimental part, p. 5343 - 5355 (2012/01/06)
Antibacterial minor groove binders related to the natural product, distamycin, are development candidates for novel antibiotics. Alkenes have been found to be effective substitutes for the isosteric amide links in some positions and alkyl groups larger th
Antimicrobial lexitropsins containing amide, amidine, and alkene linking groups
Anthony, Nahoum G.,Breen, David,Clarke, Joanna,Donoghue, Gavin,Drummond, Allan J.,Ellis, Elizabeth M.,Gemmell, Curtis G.,Helesbeux, Jean-Jacques,Hunter, Iain S.,Khalaf, Abedawn I.,Mackay, Simon P.,Parkinson, John A.,Suckling, Colin J.,Waigh, Roger D.
, p. 6116 - 6125 (2008/09/16)
The synthesis and properties of 80 short minor groove binders related to distamycin and the thiazotropsins are described. The design of the compounds was principally predicated upon increased affinity arising from hydrophobic interactions between minor groove binders and DNA. The introduction of hydrophobic aromatic head groups, including quinolyl and benzoyl derivatives, and of alkenes as linkers led to several strongly active antibacterial compounds with MIC for Staphylococcus aureus, both methicillin-sensitive and -resistant strains, in the range of 0.1-5 μg mL-1, which is comparable to many established antibacterial agents. Antifungal activity was also found in the range of 20-50 μg mL-1 MIC against Aspergillus niger and Candida albicans, again comparable with established antifungal drugs. A quinoline derivative was found to protect mice against S. aureus infection for a period of up to six days after a single intraperitoneal dose of 40 mg kg-1.
