Antitumour action

Richon, V.M. (2006) Cancer biology mechanism of antitumour action of vorinostat (suberoylanilide hydroxamic add), a novel histone deacetylase inhibitor. British Journal of Cancer, 95. S2—S6. 

The antitumour action of the natural antibiotic bleomycin is thought to involve the aerobic degradation of DNA by the Fe2+-bleomycin complex. In order to probe the mechanism of antitumour action of bleomycin, the 4-ethylamido[5,(2 -thienyl)-2-thiophene] imidazole iron(II) complex was synthesized [129]. It was studied in non-aqueous solution using cyclic voltammetry and showed antitumour activity in vitro, its action causing cleavage of the double helical DNA. 

Although the downstream events hy which cannabinoids exert their antitumoural action are not completely unravelled, there is certain evidence for the implication of at least three mechanisms tumour cell apoptosis, tumour cell growth arrest, and inhibition of tumour angiogenesis. 

Hill, S., Williams, K. B., and Denekamp, J. (1989) Vascular collapse after flavone acetic acid. A possible machanism of its antitumour action. Eur. J. Cancer Clin. Oncol. 25, 1419-1423. 

In order to clarify the mechanism of action of these compounds, their action suppressing the dehydrogenase of Ehrlich ascites carcinoma cells, and the syntheses of nucleic acids and protein by coli bacilli was examined. It was presumed from the results that the antitumour action of the compound LXII) is mainly due to the suppression of dehydrogenase action and that of compound LXIII) and compound LXIV) is due to the suppression of dehydrogenase action and syntheses of deoxyribonucleic acid, ribonucleic acid, and protein in tumour cells. 

Such reactions can also be interpreted as alkylation of the nucleophile. This explains the cytostatic and antitumour action of aziridines and of bis(2-chloroethyl)amine 1. An equilibrium exists between 1 and 1-(2-chloroethyl)aziridinium chloride 2. 

The 4,5-dihydroisoxazole structure is found in some pharmacologically interesting natural products, e.g. in the antibiotic cycloserin 5, which is used in the treatment of tuberculosis. It is also found in the antibiotic acivicine 6, an a-amino acid with antitumour action. 

Adriamycin toxicity in CBA mice bearing TLX5 lymphoma was reduced by a pharmacological dose of melatonin (20-40 mg/kg) without decreasing the antitumour action of adriamycin (Rapozzi et al. 1998). 

Although there are exceptions to this rule, any basic mechanism proposed to explain the antitumour action of these agents must take into account the necessity for di- or polyfunctionality. 

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