Mutagenic and Analgesic Activities of Aniline Derivatives

doi:10.1002/jps.2600800811

Journal of Pharmaceutical Sciences

Volume 80, Issue 8, August 1991, Pages 761-764

https://doi.org/10.1002/jps.2600800811 Get rights and content

Abstract

Phenacetin (1), acetaminophen (2), acetanilide (3), 4-aminophenol (4), and aniline (5) were tested in S.J.L. Swiss mice for their mutagenic and analgesic activities. The S-analogues of 1 and 2, 4-mercaptoacetanilide (6) and 4-ethylthioacetanilide (7), respectively, were synthesized and tested in the same way to define if both activities could be separated by molecular modification. All the compounds tested exhibited analgesic activity with ED₅₀ values ranging from 12.6 to 158.5 mg/kg. The compounds could be arranged in a decreasing order of analgesic activity as follows: 3 > 4 ≃ 5 ≃ 6 > 1 ≃ 7 > 2. All the compounds, except 6, were positive mutagens in the micronucleus test (statistically significant). The order of relative mutagenic potencies was 1≃7 > 4 > 2 ≃ 3 ≃ 5. A narrow dose–response curve relationship was found for 5 and its metabolite 4, the relative mutagenic potencies of which suggest ring hydroxylation as the major pathway of biotoxification. No parallelism was found between analgesic and mutagenic activities, so they could be separated by pharmacomodulation: 6 was more effective as an analgesic in the acetic acid test than 2, and no mutagenic activity was found at the doses assayed.

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Mutagenic and Analgesic Activities of Aniline Derivatives

Abstract

Toxicology

Mutat. Res.

Mutat. Res.

Toxicol. Appl. Pharmacol.

Pharmacol.

Toxicol. Appl. Pharmacol.

Mutat. Res.

Jpn. J. Pharmacol.

Ann. Rep. Med. Chem.

Mutat. Res.

Free Rod. Biol. Med.

Drug Design

Med. Chem.

The Haemolytic Anemias: Congenital and Acquired

Ann. Rev. Pharmacol. Toxicol.

Mutat. Res.

Cancer