title: Amino acid amides of piperic acid (PA) and 4-ethylpiperic acid (EPA) as NorA efflux pump inhibitors of Staphylococcus aureus.
abstract: A total of eighteen piperic acid (PA) and 4-ethylpiperic acid (EPA) amides (C1-C18) with α-, β- and γ-amino acids were synthesized, characterized and evaluated for their efflux pump inhibitory activity against ciprofloxacin resistant Staphylococcus aureus. The amides were screened against NorA overexpressing S. aureus SA-1199B and wild type S. aureus SA-1199 using ethidium bromide as NorA efflux pump substrate. EPI C6 was found to be most potent and reduced the MIC of ciprofloxacin by 16 fold followed by C18 which showed 4 fold reduction of MIC. Ethidium bromide efflux inhibition and accumulation assay proved these compounds as NorA inhibitors.
authors: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Naiem Ahmad
authors: NA
authors: Wani
authors: Clinical Microbiology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research, CSIR-IIIM, Canal Road, Jammu 180 001, India.
authors: Samsher
authors: S
authors: Singh
authors: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Saleem
authors: S
authors: Farooq
authors: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research, CSIR-IIIM, Canal Road, Jammu 180 001, India.
authors: Sudha
authors: S
authors: Shankar
authors: Bioorganic Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Surrinder
authors: S
authors: Koul
authors: Clinical Microbiology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research, CSIR-IIIM, Canal Road, Jammu 180 001, India. Electronic address: iakhan@iiim.ac.in.
authors: Inshad Ali
authors: IA
authors: Khan
authors: Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; Academy of Scientific and Innovative Research, CSIR-IIIM, Canal Road, Jammu 180 001, India. Electronic address: raj@iiim.ac.in.
authors: Rajkishor
authors: R
authors: Rai
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000596:Amino Acids; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002939:Ciprofloxacin; D005231:Fatty Acids, Unsaturated; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus; C017637:piperic acid
keywords: NorA efflux pump; Piperic acid; Staphylococcus aureus; β-Amino acid; γ-Amino acid