Synthesis and antimycobacterial activity of N′-[( E)-(monosubstituted-benzylidene)]-2-pyrazinecarbohydrazide derivatives

• Published in: European journal of medicinal chemistry Vol. 44; no. 12; pp. 4954 - 4959
• Main Authors: Vergara, Fátima M.F., Lima, Camilo H. da S., Henriques, Maria das Graças M. de O., Candéa, André L.P., Lourenço, Maria C.S., Ferreira, Marcelle de L., Kaiser, Carlos R., de Souza, Marcus V.N.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 01-12-2009; Elsevier
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimycobacterial activity; Antitubercular Agents - chemical synthesis; Antitubercular Agents - pharmacology; Benzylidene Compounds - chemical synthesis; Benzylidene Compounds - chemistry; Benzylidene Compounds - pharmacology; Biological and medical sciences; Cell Survival; Drug Design; Drugs; Humans; Hydrazines - chemical synthesis; Hydrazines - chemistry; Hydrazines - pharmacology; Macrophages - drug effects; Medical sciences; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis - drug effects; N-Acylhydrazones; Pharmacology. Drug treatments; Pyrazinamide - chemical synthesis; Pyrazinamide - chemistry; Pyrazinamide - pharmacology; Pyrazine; Drugs; N-Acylhydrazones; Pyrazine; Antimycobacterial activity; Organic hydrazide; Mycobacterium bovis; Nitrogen heterocycle; Benzene derivatives; In vitro; Structure activity relation; Mycobacteriales; Six membered ring; Mycobacteriaceae; Bacteria; Actinomycetes; Antituberculous agent; Hydrazone; Antibacterial agent; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2009.08.009

The present article describes a series of twenty-six
N′-[(
E)-(monosubstituted-benzylidene)]-2-pyrazinecarbohydrazide (
4–
29), which were synthesized and evaluated for their cell viabilities in non infected and infected macrophages with
Mycobacterium bovis Bacillus Calmette–Guerin (BCG). Afterwards, the non-cytotoxic compounds (
4,
6,
8,
15,
21,
23,
24,
27 and
28) were assessed against
Mycobacterium tuberculosis ATCC 27294 using the micro plate Alamar Blue assay (MABA) and the activity expressed as the minimum inhibitory concentration (MIC) in μg/mL. The compounds
6,
23,
27 and
28 exhibited a significant activity (50–100
μg/mL) when compared with first line drugs such as pyrazinamide and were not cytotoxic in their respective MIC values.
[Display omitted] A series of twenty-six pyrazine derivatives have been synthesized and evaluated against
M. tuberculosis. Compounds
6,
23,
27 and
28 exhibited a significant activity (50–100
μg/mL).