NIH COBRE Center for Structural and Functional Neuroscience, Department of Biomedical and Pharmaceutical Sciences, The University of Montana, Missoula, MT 59812, USA.
Chem Biol Drug Des. 2010 Dec;76(6):546-51. doi: 10.1111/j.1747-0285.2010.01035.x. Epub 2010 Oct 11.
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 Staphylococcus 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.
吡啶翁类肟化合物已被广泛应用于抗胆碱酯酶药物中毒的解毒剂。在化学和生物联合事件的情况下，了解解毒剂对生物威胁提供额外保护的能力是至关重要的。本文报告了一系列季铵吡啶翁类化合物对一些低致病性的生物安全等级 1 和 2 病原体的体外抗菌和抗寄生虫活性的结果。总的来说，除了噻吩和苯并噻吩取代的单季铵吡啶化合物 21 和 24 对金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌具有中等的抗菌活性，IC50 值范围为 12.2 至 17.7μg/mL 外，我们的化合物组基本没有抗菌作用。化合物 21 和 24 对利什曼原虫也表现出抗利什曼病活性，IC50 值分别为 19 和 18μg/mL。另一种具有溴丁基侧链的单季铵吡啶化合物 17 对氯喹敏感和耐药的恶性疟原虫都表现出抗疟活性，IC50 值分别为 3.7 和 4.0μg/mL。没有任何双季铵吡啶化合物表现出抗菌或抗寄生虫活性。这些化合物对哺乳动物肾成纤维细胞均无细胞毒性作用。本研究结果表明，这些吡啶类化合物，其中一些已被用作解毒剂，没有显著的抗菌和抗寄生虫活性，在发生化学-生物联合事件时，不能依赖它们提供额外的保护。
