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

Michael D. Coleman*, Daniel L. Rathbone, Rajinda Chima, Peter A. Lambert, David C. Billington

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)99-102
Number of pages4
JournalEnvironmental Toxicology and Pharmacology
Volume9
Issue number3
DOIs
Publication statusPublished - Jan 2001

Keywords

  • 2-pyridyl carboxamidrazones
  • cytotoxicity
  • tuberculosis

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