title: Small Antimicrobial Agents Based on Acylated Reduced Amide Scaffold.
abstract: Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resistant Gram-positive and Gram-negative bacterial strains. Meanwhile, they also effectively inhibit the biofilm formation. Mechanistic studies suggest that these compounds kill bacteria by compromising bacterial membranes, a mechanism analogous to that of host-defense peptides (HDPs). The mechanism is further supported by the fact that the lead compounds do not induce resistance in MRSA bacteria even after 14 passages. Lastly, we also demonstrate that these molecules have therapeutic potential by preventing inflammation caused by MRSA induced pneumonia in a rat model. This class of compounds could lead to an appealing class of antibiotic agents combating drug-resistant bacterial strains.
authors.affiliation: Department of Chemistry, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Teng
authors.affiliation: Department of Biomedical Engineering, College of Engineering and Applied Science, Nanjing University , 22 Hankou Road, Nanjing, Jiangsu 210093, P. R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Huo
authors.affiliation: Department of Chemistry, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Alekhya
authors.initials: A
authors.lastname: Nimmagadda
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health , 1415 Washington Heights, Ann Arbor, Michigan 48109, United States.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Chemistry, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Fengyu
authors.initials: F
authors.lastname: She
authors.affiliation: Department of Chemistry, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Ma
authors.initials: M
authors.lastname: Su
authors.affiliation: College of Pharmacy, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Lin
authors.affiliation: College of Pharmacy, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Chemistry, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Annie
authors.initials: A
authors.lastname: Cao
authors.affiliation: Department of Environmental Health Sciences, University of Michigan School of Public Health , 1415 Washington Heights, Ann Arbor, Michigan 48109, United States.
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Xi
authors.affiliation: Department of Biomedical Engineering, College of Engineering and Applied Science, Nanjing University , 22 Hankou Road, Nanjing, Jiangsu 210093, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Chemistry, University of South Florida , 4202 E. Fowler Avenue, Tampa, Florida 33620, United States.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
mesh_terms: D000215:Acylation; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010084:Oxidation-Reduction; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy / Q000382:microbiology; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D004151:Dipeptides