Synthesis, and antiprotozoal and antibacterial activities of S-substituted 4,6-dibromo- and 4,6-dichloro-2-mercaptobenzimidazoles.
The synthesis and some germicidal activities in vitro of two congener series of S-substituted 4,6-dihalogeno-2-mercapto-1H-benzimidazoles are reported. There was no substantial difference between antibacterial activities of corresponding 4,6-dichloro- and 4,6-dibromo-derivatives. The present results confirm lower susceptibility to substituted benzimidazoles of Gram-negative compared to Gram-positive bacteria. Minimum inhibitory concentrations (MICs) of a majority of the novel derivatives ranged between 25 and 100microg/ml for Gram-positive bacteria. The most active compounds (MICs for Gram-positive bacteria: 0.78-50microg/ml) were 4,6-dichloro-2-(4-nitrobenzylthio)-1H-benzimidazole and 4,6-dibromo-2-(4-nitrobenzylthio)-1H-benzimidazole that were 4-32 times more potent than nitrofurantoin against all Gram-positive bacteria utilized but Escherichia faecalis, against which they were, respectively, 2 and 4 times less potent than nitrofurantoin. Among Gram-negative bacteria used, Stenotrophomonas maltophilia and Bordetella bronchiseptica were most sensitive (as evidenced by a number of MICs </=100microg/ml), whereas Pseudomonas aeruginosa was most resistant to the new benzimidazole derivatives (all MICs >400microg/ml). All the new compounds were at least several times more active against Giardia intestinalis (IC(50): 0.006-0.053microg/ml), and a half of them were at least several times more active against Trichomonas vaginalis (IC(50): 0.0015-0.182microg/ml) than metronidazole (IC(50): 0.210 and 0.037microg/ml, respectively), the drug of choice in the treatment of G. intestinalis and T. vaginalis infections.
Andrzejewska
Mariola
M
Institute of Chemistry, Agricultural University, 159C Nowoursynowska Street, 02-787, Warsaw, Poland. kazimierczuk@delta.sggw.waw.pl
Yepez-Mulia
Lilian
L
Tapia
Amparo
A
Cedillo-Rivera
Roberto
R
Laudy
Agnieszka E
AE
Starościak
Bohdan J
BJ
Kazimierczuk
Zygmunt
Z
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D016829:Giardia lamblia / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009152:Mutagenicity Tests; D014246:Trichomonas vaginalis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D001562:Benzimidazoles