title: Antibacterial, antifungal and antileishmanial activities of indolone-N-oxide derivatives.
abstract: An alarming increase in microbial resistance to traditional drugs and classical pharmacophores has spurred the search for new antimicrobial compounds. Indolone-N-oxides (INODs) possess a redox pharmacophore with promising, recently established, antimalarial activities. In this study, the anti-infectious properties of a series of INODs were investigated. The antibacterial activity was evaluated against five bacterial strains Gram-positive (Staphylococcus aureus, Enterococcus hirae), Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and acid-fast (Mycobacterium tuberculosis). The antifungal activity was assessed using two fungal strains (Aspergillus niger, Candida albicans). The antileishmanial activity was tested against two leishmanial strains, axenically-cultured amastigote (Leishmania infantum, Leishmania amazonensis). The pharmacological activities are discussed as a function of structural and lipophilic characteristics. The Gram-positive bacterial strain E. hirae was found to be the most sensitive strain, whereas the Gram-negative E. coli was resistant to this family of compounds. One compound (64) was more potent than nalidixic acid against E. hirae, whereas another one (52) was equipotent as clotrimazole against C. albicans. INODs were microbe -cidal rather than -static. INODs showed good antitubercular activity in the low micromolar range (similar to ciprofloxacin). In addition, INOD-antiprotozoal potencies were confirmed against the leishmania parasite. INODs showed a broad spectrum of antimicrobial activity and offer a promising anti-infectious prototype worthy of being developed.
authors: Toulouse University III, UPS, UMR 152 (PHARMA-DEV), Toulouse, France. hanygamal85@hotmail.com
authors: Hany
authors: H
authors: Ibrahim
authors: Aurelie
authors: A
authors: Furiga
authors: Ennaji
authors: E
authors: Najahi
authors: Christel
authors: C
authors: Pigasse Hénocq
authors: Jean-Pierre
authors: JP
authors: Nallet
authors: Christine
authors: C
authors: Roques
authors: Agnes
authors: A
authors: Aubouy
authors: Michel
authors: M
authors: Sauvain
authors: Patricia
authors: P
authors: Constant
authors: Mamadou
authors: M
authors: Daffé
authors: Françoise
authors: F
authors: Nepveu
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D050296:Microbial Viability / Q000187:drug effects; D010087:Oxides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D007211:Indoles; D010087:Oxides