title: In vitro antibacterial activities of p-toluenesulfonyl-hydrazinothiazoles and hydrazinoselenazoles against multi-drug resistant Gram-negative phenotypes.
abstract: BACKGROUND
  Bacterial multidrug resistance (MDR) constitutes a major hurdle in the treatment of infectious diseases worldwide. The present study was designed to evaluate the antibacterial activities of synthetic p-toluenesulfonyl-hydrazinothiazoles against multidrug resistant Gram-negative bacteria.
  
  
  METHODS
  The broth microdilution method was used to determine the minimal inhibitory concentrations (MIC).
  
  
  RESULTS
  The results demonstrated that the best activities were obtained with hydrazinoselenazoles. p-Chloro-benzyliden-selenosemicarbazide, 4-methyl-2-[(4-chloro-benzyliden)-hydrazinyl]-1,3-selenazole, p-chloro-benzoyl-selenosemicarbazide and 4-chloromethyl-2-[(4-chlorobenziliden)-N-acetyl-hydrazinyl]-1,3-selenazole were more active than the choramphenicol on Klebsiella pneumoniae KP63. Tested alone, the lowest MIC value of 16 mg/L was obtained with p-methoxy-benzyliden-selenosemicarbazide against Enterobacter aerogenes ATCC13048, K. pneumoniae ATCC112296 and KP55. Tested in the presence of an efflux pump inhibitor, phenylalanine arginine β-naphthylamide (PAβN), the activity of p-chloro-benzyliden-selenosemicarbazide, 4-methyl-2-[(4-chloro-benzyliden)-hydrazinyl]-1,3-selenazole, p-chloro-benzoyl-selenosemicarbazide and p-methoxy-benzyliden-selenosemicarbazide significantly increased with MIC values below 10 mg/L obtained respectively on 43.8 %, 31.3 %, 62.5 % and 100 % of the 16 tested bacterial strains. The lowest MIC value of 0.5 mg/L in the presence of PAβN was recorded with p-chloro-benzoyl-selenosemicarbazide against Escherichia coli ATCC8739 and KP55 as well as p-methoxy-benzyliden-selenosemicarbazide against E. aerogenes KP55. p-Chloro-benzyliden-selenosemicarbazide and p-chloro-benzoyl-selenosemicarbazide contained the same pharmacophore as p-methoxy-benzyliden-selenosemicarbazide.
  
  
  CONCLUSIONS
  This study indicates that p-chloro-benzyliden-selenosemicarbazide, p-chloro-benzoyl-selenosemicarbazide and p-methoxy-benzyliden-selenosemicarbazide could be explored more to develop novel antimicrobial drugs to fight MDR bacterial infections.
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon. armkuete@yahoo.fr.
authors.forename: Armelle T
authors.initials: AT
authors.lastname: Mbaveng
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. a2rianaig@yahoo.com.
authors.forename: Adriana Grozav
authors.initials: AG
authors.lastname: Ignat
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Chemistry, Faculty of Medicine and Biomedical Sciences University of Yaoundé I, Yaoundé, Cameroon. bath_ngameni@yahoo.fr.
authors.forename: Bathélémy
authors.initials: B
authors.lastname: Ngameni
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. vzaharia@umfcluj.ro.
authors.forename: Valentin
authors.initials: V
authors.lastname: Zaharia
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon. btngadjui@yahoo.fr.
authors.forename: Bonaventure T
authors.initials: BT
authors.lastname: Ngadjui
authors.affiliation: Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon. kuetevictor@yahoo.fr.
authors.forename: Victor
authors.initials: V
authors.lastname: Kuete
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D021902:Enterobacter aerogenes / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D012663:Semicarbazides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D014105:Tosyl Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D006834:Hydrazines; D049990:Membrane Transport Modulators; D016566:Organoselenium Compounds; D012663:Semicarbazides; D013844:Thiazoles; D014105:Tosyl Compounds