Antitumor drugs evaluation

Dihydropyrrolizines 272, their salts and solvates, were prepared and evaluated as potential antitumor drugs or as site-specific DNA alkylating agents in the gene-relating technologies <1998WO9827095>. 

Merisko-Liversidge, E., Sarpotdar, P, Bruno, J., Hajj, S., Wei, L., Peltier, N., Rake, J., etal. (1996) Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs, Pharm. Res., 13 272-278. 

The aim of the present contribution is to critically review computational work related to platinum antitumor drugs, published prior to 1998. After a section devoted to molecular-orbital calculations on platinum antitumor complexes and related compounds, we address force-field calculations on platinum adducts with DNA constituents that have been used (mainly in combination with NMR spectroscopy) to evaluate the structure of the adduct. A brief outlook concludes this chapter. 

Enough material was amassed to begin the evaluation of this class of agents as antitumor drugs, initially by the production of epothilones A and B (Figure 8.11) through a combination of classical fermentation and isolation of... 

The differences revealed in the gel electrophoretic pattern of the nucleosome core particle after binding cis- and trans-DPP (10) could possibly provide a simple in vitro screen for pTatinum antitumor drug activity. Preliminary studies (12) have shown that nucleosome cores incubated with either dichloroethylenediamine-platinum(II) or cis-dichlorobis(isopropylamine)-platinum(II), two known antitumor drugs, exhibit gel electrophoretic patterns very similar to those of nucleosome cores incubated with cis-DDP. Incubation with [(terpy)PtCl]Cl, an inactive compound, gave very different gel patterns. Further work is in progress to evaluate the utility of this assay. 

The in vitro methods by which macromolecular anticancer drug conjugates are evaluated for efficacy are similar to those used to screen for the anticancer activity of low molecular weight compounds. A thorough review of in vitro models used for the evaluation of antitumor therapy was published several years ago [174]. 

Some of these cytotoxic marine alkaloids are promising candidates for new drugs. For example, ecteinascidins, Fig. (29) are a family of tetrahydroisoquinolone alkaloids isolated from the Caribbean tunicate Ecteinascidici turbinata, which have been selected for clinical development. These compounds are presently in pre-clinical and clinical trials for human cancers [221-225], A series of totally synthetic molecules that are structurally related to the ecteinascidins is currently being prepared and evaluated as antitumor agents [226],... 

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