Sławiński Jarosław, Pogorzelska Aneta, Zołnowska Beata, Kędzia Anna, Ziółkowska-Klinkosz Marta, Kwapisz Ewa
Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, Poland.
Department of Oral Microbiology, Medical University of Gdańsk, ul. Do Studzienki 38, Gdańsk 80-227, Poland.
Molecules. 2014 Sep 2;19(9):13704-23. doi: 10.3390/molecules190913704.
Pathogenic fungi are one of the main causes of hospital-related infections. Since conventional antifungals have become less effective because of the increasing fungal resistance to the standard drugs, the need for new agents is becoming urgent. Herein we report a synthesis of a series of novel N-[imino-(1-oxo-(1H)-phthalazin-2-yl)methyl]-benzenesulfonamide derivatives with in vitro activity against yeast-like fungi isolated from the oral cavity and respiratory tract of patients with candidiasis. These compounds were synthesized by the one-step or two-step reactions of 1-(2-alkylthiobenzensulfonyl)-2-aminoguanidines with the appropriate ortho-carbonyl benzoic acids. The biological study revealed that new derivatives have shown significant growth-inhibitory activity, superior or comparable, than those of the reference drug fluconazole. The most promising activities were observed against Candida albicans, with inhibition at least 1-3 (12.5%-37.5%) of the eight tested strains at the low MIC level of ≤6.2-25 µg/mL.
致病性真菌是医院相关感染的主要原因之一。由于真菌对标准药物的耐药性增加，传统抗真菌药物的效果越来越差，因此对新型药物的需求变得迫切。在此，我们报告了一系列新型N-[亚氨基-(1-氧代-(1H)-酞嗪-2-基)甲基]-苯磺酰胺衍生物的合成，这些衍生物对从念珠菌病患者口腔和呼吸道分离出的酵母样真菌具有体外活性。这些化合物是通过1-(2-烷硫基苯磺酰基)-2-氨基胍与适当的邻羰基苯甲酸的一步或两步反应合成的。生物学研究表明，新衍生物显示出显著的生长抑制活性，优于或与参考药物氟康唑相当。在≤6.2-25 µg/mL的低MIC水平下，对白色念珠菌观察到最有前景的活性，对八个测试菌株中的至少1-3个（12.5%-37.5%）有抑制作用。
