NOVEL GUANIDINE COMPOUND AGAINST MULTIDRUG-RESISTANT CYSTIC FIBROSIS-ASSOCIATED BACTERIAL SPECIES

LAMBERTI, YANINA ANDREA; ERBEN, MAURICIO FEDERICO; SAEED, AAMER; BOSCH, MARÍA ALEJANDRA

Congreso; LXV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2017

Chronic pulmonary infection is a hallmark of lung disease in cystic fibrosis (CF). Infections dominated by non-fermentative Gram-negative bacilli are particularly difficult to treat and highlight an urgent need for develop new class of agents to treat these infections. In this work, a small library comprising 13 novel thiourea and guanidine derivatives with low molecular weight were synthetized and studied as antimicrobial agents. The identity of the products was confirmed by FTIR, 1H-NMR, 13C-NMR spectra and elemental analysis. All obtained compounds were tested in vitro for their minimum inhibitory concentration (MIC) and their minimum bactericidal concentration (MBC) against two standard Gram negative non-fermentative bacilli species, Pseudomamonas aeruginosa PAO1 and Burkholderia cenocepacia J2315, and a panel of drug-resistant non-fermentative Gram-negative bacilli clinical isolates recovered from patients with CF (n=37). One novel compound, a guanidine derivative bearing adamantane-1-carbonyl and 2-bromo-4,6-difluouro-phenyl substituents (H-BDF), showed a MIC value less than 2 g/ml against the standard strains and superior activity than the standard drugs tobramycin, ceftazimide and meropenem, pointing to its potential for further development as a novel antibacterial drug.