Preliminary in vitro toxicological evaluation of a series of 2-pyridylcarboxamidrazone candidate anti-tuberculosis compounds III

Coleman, Michael D., Rathbone, Daniel L., Chima, Rajinda, Lambert, Peter A. and Billington, David C. Preliminary in vitro toxicological evaluation of a series of 2-pyridylcarboxamidrazone candidate anti-tuberculosis compounds III. Environmental Toxicology and Pharmacology, 9 (3), pp. 99-102.

Abstract

We have evaluated the cytotoxicity of a series of novel anti-tubercular 2-pyridyl carboxamidrazones through incubation with human mononuclear leucocytes (MNL), with and without a rat microsomal metabolising system. Isoniazid (INH), the closest structurally related agent, was used as a positive control. Incubation of the 3-benzyloxy-benzylidene, dimethylpropyl-benzylidene and 4-phenyl-benzylidene with MNL showed no significant toxicity in comparison with either INH or DMSO vehicle control. However, the 4-N,N-dimethylamino-1-naphthylidene derivative exerted more than sevenfold greater toxicity compared with INH, while the 4-N,N-dimethylamino-1-naphthylidene, 2-benzyloxy-3-methoxy-benzylidene, 2-t-butylthio-benzylidene and 4-i-propyl-benzylidene derivatives showed toxicity which ranged from five to fourfold that of INH. In the presence of either rat microsomes with or without NADPH, the 3-benzyloxy-benzylidene, dimethylpropyl-benzylidene and 4-phenyl-benzylidene derivatives showed no metabolically-mediated cytotoxicity. The latter two derivatives showed a combination of low toxicity and considerable efficacy against Mycobacteria tuberculosis in vitro and show promise for future development. © 2001 Elsevier Science B.V.

Publication DOI: https://doi.org/10.1016/S1382-6689(00)00067-3
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Applied Health Research Group
Life & Health Sciences > Biomedical Sciences research group
Life & Health Sciences > Health Sciences
Uncontrolled Keywords: 2-pyridyl carboxamidrazones,cytotoxicity,tuberculosis,Toxicology,Health, Toxicology and Mutagenesis,Pharmacology
Full Text Link: http://www.scopus.com/inward/record.url?scp=0035122724&partnerID=8YFLogxK
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Authors: Coleman, Michael D.
Rathbone, Daniel L.
Chima, Rajinda
Lambert, Peter A.
Billington, David C.

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