In vitro screening of pentamidine analogs against bacterial and fungal strains.
A series of linear pentamidine analogs exhibiting low cytotoxicity, active against Pneumocystis carinii, were evaluated for in vitro activities against bacterial and fungal strains. The majority of the tested bis-amidines exhibited marked activities against Gram-positive strains. In view of the fact that the highest potency was found for 1,5-bis(4-amidinophenoxy)-3-thiapentane dihydrochloride 1j with the S atom in the middle of the aliphatic linker, four new pentamidines bearing S atoms were synthesized and also evaluated against MRSA strains. N,N'-Dialkylated pentamidines with S atoms in the linker are the promising lead structures for antimicrobials development.
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland. Electronic address: dmaciejewska@wum.edu.pl.
Dorota
D
Maciejewska
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
Jerzy
J
Żabiński
Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
Paweł
P
Kaźmierczak
Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
Karolina
K
Wójciuk
Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland; Department of Molecular Biology and Translational Research, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland.
Marcin
M
Kruszewski
National Medicines Institute, Department of Antibiotics and Microbiology, 30/34 Chełmska, 00-725 Warsaw, Poland.
Hanna
H
Kruszewska
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005658:Fungi / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010419:Pentamidine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D010419:Pentamidine
Anti-MRSA activity; Anti-bacterial activity; Anti-fungal activity; Linear pentamidine analogs; Structure–activity