Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones as antimicrobial agents

• Published in: Bioorganic & medicinal chemistry Vol. 12; no. 9; pp. 2151 - 2161
• Main Authors: Bonde, Chandrakant G., Gaikwad, Naresh J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-05-2004; Elsevier Science
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimicrobial; Biological and medical sciences; Drug Evaluation, Preclinical; General aspects; Hemolytic assay; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Pyrazines - chemistry; Species Specificity; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Thiazolidinones; Thiazoline; Antimicrobial; Thiazoline; Thiazolidinones; Hemolytic assay; Organic hydrazide; Nitro compound; Bacillus subtilis; Nitrogen heterocycle; Escherichia coli; Thiazole derivatives; Salmonella typhi; Bacillaceae; Antimicrobial agent; Bacillales; Structure activity relation; Bacteria; Micrococcales; Micrococcaceae; Antituberculous agent; Chemical synthesis; Staphylococcus aureus; Enterobacteriaceae; Sulfur nitrogen heterocycle; Pyrazine derivatives; Organic bromine compounds; Organic chlorine compounds; In vitro; Mycobacterium tuberculosis; Mycobacteriales; Mycobacteriaceae; Actinomycetes; Antibacterial agent
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2004.02.024

Graphic
A series of
N
′-[3,4-disubstituted-1,3-thiazol-2(3H)-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide
11–
66 and
N
′-[(2Z)-3-(4-bromophenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-2-(pyrazin-2-yloxy)acetohydrazide
68–
74 were synthesized using appropriate synthetic route. The entire test compounds
11–
66 and
68–
74 were assayed in vitro for antibacterial activity against two different strains of Gram-negative (
E. coli and
S. typhi), Gram-positive (
S. aureus and
B. subtilis) bacteria and the antimycobacterial activity was evaluated against H
37Rv strain of
Mycobacterium tuberculosis. The minimum inhibitory concentration (MIC) was determined for test compounds and for reference standards. The test compounds showed significant antibacterial and antimycobacterial activity against the microbial strains used, when tested in vitro. In general, pyrazine ring and substituted thiazoline ring are essential for antimicrobial activity. Among the compounds tested, compounds
11,
12 and
40 were found to be most potent. The toxicity of most potent compounds
11,
12 and
40 were determined using hemolytic assay and minimal hemolytic concentration (MHCs) were determined. The test compounds were found to be nontoxic up to a dose level of 250
μg/mL.