TY - JOUR
T1 - Fungicidal effects of some derivatives of 2-ferrocenyl-benzimidazoles
T2 - A possible template for antifungal drug design
AU - Abu-Elteen, Khaled H.
AU - Abdel-Jalil, Raid J.
AU - Hamad, Mawieh A.
AU - Ghaleb, M.
AU - Khen, Khalid M.
AU - Voelter, W.
PY - 2008/12/15
Y1 - 2008/12/15
N2 - The minimum inhibitory concentration (MIC) and minimum, fungicidal concentration (MFC) for a group of newly synthesized derivatives of 2-ferrocenyl-5-fluoro-6-(4-substituted-1-pipera-zinyl) benzimidazoles were determined using a broth macrodilution method following clinical and laboratory standards institute (CLSI) recommendation for medically important Candida sp. The data demonstrate that compounds 4-fluoro-5-(4-methyl-1-piperazinyl)-2-nitroaniline(5a), 4-Fluoro-5-(4-phenyl-1-piperazinyl)-2-nitroaniline(5b), 2-ferrocenyl-5-fluoro-6-(4-methyl-1-piperazinyl) benzimidazole (7a), 2-ferrocenyl-5-fluoro-6-(4-phenyl-1-piperazinyl) benzimidazole (7b) and 2-ferrocenyl-5-fluoro-6-[4-(4-fluorophenyl)-1-piperazinyl] benzimidazole (7e) were found to have potent in vitro antiftingal activity with MICs at which 80% of the strains were inhibited (MIC80s) of 15-125 μg mL-1. The active compounds were further screened in order to establish their mode of action on the basis of inhibitory effects on growth, budding, germ-tube formation and leakage of cytoplasmic content release after treatment. In comparison to control drugs (e.g., nystatin, miconazole nitrate, and ketoconazole). Some derivatives of the 4-fluoro-5-(4-substituted-1-piperazinyl)-2-nitroanilines (series 5) and 2-ferrocenyl-5-fluoro-6-(4-substituted-1-piperazinyl)-[1H] benzi-midazoles (series 7) were found to be more potent in lower micro-molar concentrations (15-500 μg mL-1). It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and in vivo efficacies of these compounds are warranted to determine their clinical potential.
AB - The minimum inhibitory concentration (MIC) and minimum, fungicidal concentration (MFC) for a group of newly synthesized derivatives of 2-ferrocenyl-5-fluoro-6-(4-substituted-1-pipera-zinyl) benzimidazoles were determined using a broth macrodilution method following clinical and laboratory standards institute (CLSI) recommendation for medically important Candida sp. The data demonstrate that compounds 4-fluoro-5-(4-methyl-1-piperazinyl)-2-nitroaniline(5a), 4-Fluoro-5-(4-phenyl-1-piperazinyl)-2-nitroaniline(5b), 2-ferrocenyl-5-fluoro-6-(4-methyl-1-piperazinyl) benzimidazole (7a), 2-ferrocenyl-5-fluoro-6-(4-phenyl-1-piperazinyl) benzimidazole (7b) and 2-ferrocenyl-5-fluoro-6-[4-(4-fluorophenyl)-1-piperazinyl] benzimidazole (7e) were found to have potent in vitro antiftingal activity with MICs at which 80% of the strains were inhibited (MIC80s) of 15-125 μg mL-1. The active compounds were further screened in order to establish their mode of action on the basis of inhibitory effects on growth, budding, germ-tube formation and leakage of cytoplasmic content release after treatment. In comparison to control drugs (e.g., nystatin, miconazole nitrate, and ketoconazole). Some derivatives of the 4-fluoro-5-(4-substituted-1-piperazinyl)-2-nitroanilines (series 5) and 2-ferrocenyl-5-fluoro-6-(4-substituted-1-piperazinyl)-[1H] benzi-midazoles (series 7) were found to be more potent in lower micro-molar concentrations (15-500 μg mL-1). It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and in vivo efficacies of these compounds are warranted to determine their clinical potential.
KW - Antifungal susceptibility
KW - Benzimidazoles derivatives
KW - Candida sp
KW - Drug design
KW - Virulence factors
UR - http://www.scopus.com/inward/record.url?scp=67649543809&partnerID=8YFLogxK
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U2 - 10.3923/jms.2008.673.681
DO - 10.3923/jms.2008.673.681
M3 - Article
AN - SCOPUS:67649543809
SN - 1682-4474
VL - 8
SP - 673
EP - 681
JO - Journal of Medical Sciences
JF - Journal of Medical Sciences
IS - 8
ER -