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7081299 
Journal Article 
INSIGHTS INTO MYCOBACTERIAL ACTIVITY AND CYTOTOXICITY OF SUBSTITUED ISOXAZOLE-4-CARBOHYDRAZIDE DERIVATIVES 
Ploszaj, P; Junka, A; Szponar, B; Maczynski, M; Ryng, S; Bartoszewicz, M; Piwowar, A; , 
2018 
Yes 
Acta Poloniae Pharmaceutica
ISSN: 0001-6837 
POLSKIE TOWARZYSTWO FARMACEUTYCZNE 
WARSAW 
637-647 
WOS:000444460300007 
The purpose of this study was to evaluate the antimycobacterial activity of novel derivatives of 5- ino-3-methyl-4-ismazolecarboxylic acid hydrazide 1, isoniazid (INH) structural analogue. A set of 5-amino-3-methyl-4-isoxazoleairboxylic acid hydrazide 1 derivatives 2a-j have been obtained by condensation reactions with aldehydes and further transformed by cyclization with corresponding orthoesters to 5-amino-3-methylisoxazole[5,4-d]pyrimidin-4-one derivatives 3a-j and 4a-j. From the structural and functional point of view, all these products proved to be biologically important and could be used as substrates for further synthesis. 21 out of 31 structures were newly developed. Described compounds were screened against Mycobacterium fortuitum in MABA test. The most active compounds: 2e (5-amino-3-methyl-N'-((E)-(4-nitrophenyl)methylidene)-1,2-oxazole-4-carbohydrazide) and 2g (5-amino-N'-((E)-(2,4-dichlorophenyl)-methylidene)-3-methyl-1,2-oxazole-4-carbohydrazide) revealed minimum inhibitory concentration at 16 eg/mL. These compounds have been screened for toxicity profile. Low cytotoxicity against lung (A549) and fibroblasts (L929) cell lines was determined. The results demonstrated the potential and importance of further development of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide derivatives as a new class of antimycobacterial compounds and creates a possible direction in the basic research of medicinal chemistry.