title: Synthesis of novel isothiazolopyridines and their in vitro evaluation against Mycobacterium and Propionibacterium acnes.
abstract: In this paper we describe synthesis, structures and some physicochemical properties of 20 isothiazolopyridines 8-13 substituted differently into an isothiazole ring as well as their in vitro antibacterial assays against Mycobacterium tuberculosis H37Rv, Mycobacterium fortuitum PCM 672 and Propionibacterium acnes PCM 2400. Compound 13a was found to be the most active derivative against M. tuberculosis H37Rv, demonstrating 100% growth inhibition of microorganisms in the primary screen (minimum inhibitory concentration [MIC] 6.25μg/mL). Nineteen of the prepared compounds were evaluated against M. fortuitum PCM 672 and P. acnes PCM 2400 and only compounds 9 and 12d exhibited excellent activity against individual strains of microorganisms with MIC90 <1μg/mL. The inhibitory action of the remaining isothiazolopyridines towards the tested strains of the microorganism was low, absent, or a non-linear correlation prohibited accurate determination of MIC values. Unexpectedly, seven of the remaining isothiazolopyridines tested against M. fortuitum and P. acnes stimulated growth of the microorganisms in the range 10-50% or even more (10b) under experimental conditions.
authors.affiliation: Department of Chemistry of Drugs, Wrocław Medical University, Borowska 211, 50-556 Wrocław, Poland.
authors.forename: Wiesław
authors.initials: W
authors.lastname: Malinka
authors.forename: Piotr
authors.initials: P
authors.lastname: Swiątek
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sliwińska
authors.forename: Bogumiła
authors.initials: B
authors.lastname: Szponar
authors.forename: Andrzej
authors.initials: A
authors.lastname: Gamian
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Karczmarzyk
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fruziński
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009161:Mycobacterium / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011425:Propionibacterium acnes / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D011725:Pyridines; D013844:Thiazoles
keywords: Antibacterial activity; Antimycobacterial agents; Isothiazolopyridine; Synthesis