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Antimicrobial, Antimalarial, and Antileishmanial Activities of Mono‐ and Bis‐quaternary Pyridinium Compounds
Author(s) -
Bharate Sandip B.,
Thompson Charles M.
Publication year - 2010
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2010.01035.x
Subject(s) - antiprotozoal , pyridinium , antimicrobial , chemistry , pyridinium compounds , plasmodium falciparum , staphylococcus aureus , combinatorial chemistry , stereochemistry , pharmacology , in vitro , biochemistry , organic chemistry , biology , bacteria , malaria , immunology , genetics
Pyridinium‐based oxime compounds have been utilized worldwide as antidotes following exposure to anticholinesterase agents. In the event of combined chemical and biological incident, it is of vital importance to know the ability of antidotes to provide additional protection against biological threats. This paper reports results of in vitro antimicrobial and antiprotozoal activities of a series of quaternary pyridinium oximes against a number of lower pathogenicity BSL‐1 and 2 agents. In general, our compound panel had little to no antimicrobial action except for thiophene‐ and benzothiophene‐substituted monoquaternary pyridinium compounds 21 and 24 that showed moderate antibacterial activity against Staphylococus aureus and methicillin‐resistant S. aureus with IC 50 values ranging from 12.2 to 17.7 μg/mL. Compounds 21 and 24 also exhibited antileishmanial activity against Leishmania donovani with IC 50 values of 19 and 18 μg/mL, respectively. Another monoquaternary pyridinium compound with a bromobutyl side chain 17 showed antimalarial activity against both a chloroquine sensitive and resistant strains of Plasmodium falciparum with IC 50 values of 3.7 and 4.0 μg/mL, respectively. None of the bisquaternary pyridinium compounds showed antimicrobial or antiprotozoal activity. None of the compounds showed cytotoxic effects toward mammalian kidney fibroblasts. Results of this study indicate that the pyridinium compounds, some of which are already in use as antidotes, do not have significant antimicrobial and antiprotozoal activities and cannot be relied upon for additional protection in the event of combined chemical–biological incident.