Division of Pharmaceutical Biology, Faculty of Pharmacy, P. O. Box 56 (Biocenter 1), FIN-00014 University of Helsinki, Finland.
Z Naturforsch C J Biosci. 2011 Nov-Dec;66(11-12):571-80. doi: 10.1515/znc-2011-11-1206.
Substituted salicylaldehydes are potent antibacterial and antifungal agents and may have chemotherapeutic potential. In the clinical setting, the minimal inhibitory concentration (MIC) as well as the minimal bactericidal and fungicidal concentrations (MBC and MFC, respectively) are of fundamental interest. Therefore, we have now, using a panel of five microbial species (Bacillus cereus, Candida albicans, Escherichia coli, Saccharomyces cerevisiae, and Staphylococcus aureus), determined the MIC and MBC/MFC values of a total of 22 aromatic aldehydes, including 19 substituted salicylaldehydes and the unsubstituted parent compounds benzaldehyde and salicylaldehyde (2-hydroxybenzaldehyde). The results clearly indicate that both of the yeasts studied are remarkably sensitive to various salicylaldehydes and, especially, to halogenated ones. Some congeners clearly merit consideration as potential therapeutic agents for Candida infections. The MIC values of the most potent congeners are of roughly the same magnitude as that of amphotericin B, and the results of the MFC measurements indicate that the compounds are fungicidal. All of the bacteria studied are also sensitive to at least some of the compounds tested but, clearly, this class of antimicrobials has superior activity against yeasts. Structure-activity relationships are discussed for each microbial species and compared with each other. The comparison of the results of MIC and MBC/MFC measurements with those of agar diffusion tests revealed aspects that are of interest concerning the methodology of antimicrobial activity screening. Unexpectedly, it was found that some compounds that are completely devoid of activity in agar diffusion tests had potent activity in MIC tests, indicating that if only agar diffusion methodology is used in drug discovery, some highly active compounds may be missed.
取代水杨醛是一种有效的抗菌和抗真菌试剂，并且可能具有化疗潜力。在临床环境中，最小抑菌浓度（MIC）以及最小杀菌和抑菌浓度（MBC 和 MFC）是基本的关注点。因此，我们现在使用五微生物种（蜡状芽孢杆菌、白色念珠菌、大肠杆菌、酿酒酵母和金黄色葡萄球菌）的检测方法，测定了总共 22 种芳香醛的 MIC 和 MBC/MFC 值，包括 19 种取代水杨醛和未取代的母体化合物苯甲醛和水杨醛（2-羟基苯甲醛）。结果清楚地表明，所研究的两种酵母对各种水杨醛，特别是卤代水杨醛非常敏感。一些同系物显然值得考虑作为治疗白色念珠菌感染的潜在治疗剂。最有效的同系物的 MIC 值与两性霉素 B 的大致相同，并且 MFC 测量结果表明这些化合物具有杀菌作用。所研究的所有细菌至少对测试的某些化合物敏感，但显然，这类抗菌剂对酵母具有更好的活性。讨论了每个微生物种的结构-活性关系，并相互进行了比较。MIC 和 MBC/MFC 测量结果与琼脂扩散测试结果的比较揭示了有关抗菌活性筛选方法学的方面的一些有趣问题。出乎意料的是，发现一些在琼脂扩散测试中完全没有活性的化合物在 MIC 测试中具有很强的活性，这表明如果仅在药物发现中使用琼脂扩散方法学，可能会错过一些具有高度活性的化合物。
