Menogaril, an Anthracycline Compound with a Novel Mechanism of Action: Cellular Pharmacology

Overview

Journal Jpn J Cancer Res

Specialty Oncology

Date 1990 Aug 1

PMID 2144516

Citations 2

Authors

K Wierzba

Y Sugimoto

K Matsuo

T Toko

S Takeda

Y Yamada

S Tsukagoshi

Affiliations

Soon will be listed here.

Abstract

Menogaril, an anthracycline compound possessing a significant antitumor activity after both po and iv administration, has been introduced into clinical trials. However, its mechanism of action has not been clarified yet. This study revealed that its cytotoxicity correlated very well with the inhibition of macromolecular synthesis, indicating the involvement of interaction with DNA. The spectrophotometric study showed a weaker binding of this compound to calf thymus DNA when compared to that of doxorubicin (adriamycin). Despite the lower binding affinity of menogaril to DNA, pronounced DNA cleavage was observed in an intact cell system, indicating that the character of the interaction with DNA is different from intercalation. In contrast to doxorubicin, menogaril is extensively localized in the cytoplasm. The cytoplasmic localization prompted us to study its effect on cytoskeleton proteins. It was found that menogaril inhibited the initial polymerization rate of tubulin, indicating a possible contribution of this process to the overall cytotoxicity of menogaril.

Citing Articles

Phase I clinical and pharmacokinetic study of menogaril (7-con-O-methylnogarol) in previously treated patients with acute leukemia.

Mazurek C, Dutcher J, Schwartz E, Garl S, Benson L, Wiernik P Invest New Drugs. 1993; 11(4):313-22.

PMID: 8157473 DOI: 10.1007/BF00874430.

Menogaril, an anthracycline derivative, inhibits DNA topoisomerase II by stabilizing cleavable complexes.

Ono K, Ikegami Y, Nishizawa M, Andoh T Jpn J Cancer Res. 1992; 83(9):1018-23.

PMID: 1331004 PMC: 5918973. DOI: 10.1111/j.1349-7006.1992.tb02016.x.

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