title: Synthesis and anti-yeast evaluation of novel 2-alkylthio-4-chloro-5-methyl-N-[imino-(1-oxo-(1H)-phthalazin-2-yl)methyl]benzenesulfonamide derivatives.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, Poland. jaroslaw@gumed.edu.pl.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Sławiński
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, Poland. anetapogorzelska@gumed.edu.pl.
authors.forename: Aneta
authors.initials: A
authors.lastname: Pogorzelska
authors.affiliation: Department of Organic Chemistry, Medical University of Gdańsk, Al. Gen. J. Hallera 107, Gdańsk 80-416, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Zołnowska
authors.affiliation: Department of Oral Microbiology, Medical University of Gdańsk, ul. Do Studzienki 38, Gdańsk 80-227, Poland. anak@gumed.edu.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Kędzia
authors.affiliation: Department of Oral Microbiology, Medical University of Gdańsk, ul. Do Studzienki 38, Gdańsk 80-227, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Ziółkowska-Klinkosz
authors.affiliation: Department of Oral Microbiology, Medical University of Gdańsk, ul. Do Studzienki 38, Gdańsk 80-227, Poland. kwapisz@gumed.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kwapisz
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009055:Mouth / Q000382:microbiology; D012137:Respiratory System / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D013449:Sulfonamides; D015725:Fluconazole