Anticancer drugs molecular modeling

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]. 

Molecular mechanics and dynamics studies of metal-nucleotide and metal-DNA interactions to date have been limited almost exclusively to modeling the interactions involving platinum-based anticancer drugs. As with metal-amino-acid complexes, there have been surprisingly few molecular mechanics studies of simple metal-nucleotide complexes that provide a means of deriving reliable force field parameters. A study of bis(purine)diamine-platinum(II) complexes successfully reproduced the structures of such complexes and demonstrated how steric factors influenced the barriers to rotation about the Pt(II)-N(purine) coordinate bonds and interconversion of the head-to-head (HTH) to head-to-tail (HTT) isomers (Fig. 12.4)[2011. In the process, force field parameters for the Pt(II)/nucleotide interactions were developed. A promising new approach involving the use of ab-initio calculations to calculate force constants has been applied to the interaction between Pt(II) and adenine[202]. 

The present modeling approach to circadian cancer chronotherapy is based on an automaton model for the cell cycle. Continuous approaches to cell cycle progression have also been used to study the link between cell proliferation and circadian rhythms [44] and to determine, in conjunction with optimal control theory, the most efficient circadian schedules of anticancer drug administration [45]. Including more molecular details of the cell cycle in continuous models for cell populations represents a promising line for future research. Hybrid models incorporating molecular details into the automaton approach presented here will also likely be developed. 

W. J. Zeller, M. D Incalci, and D. R. Newell, Novel Approaches in Anticancer Drug Design Molecular Modeling - New Treatment Strategies. International Symposium on Novel Approaches in Cancer Therapy, Heidelberg, December 1-4, 1993, in Contrib. Oncol., Vol. 49, Karger, Basel, 1995. 

DNA is believed to be the most important cellular target of titanocene dichloride anticancer drugs when 3 is reacted with a diorganophosphate a chloride-free 1 2 (Ti P) adduct can be isolated, which shows coordination between titanium and the phosphate groups [44]. Recently, a molecular modelling study [45] was able to... 

His research interests include the design and synthesis of selective anticancer agents, the molecular modelling of drug-DNA interactions and the design of prodrugs for the treatment of nephropathic cysdnosis. 

One single report on theoretical work in this area has appeared, in 1992 <92JMC3377> the molecular modeling of the well-known anticancer drug Temozolomide (12) has been carried out, and the net charges of the ring atoms have been calculated. 

Frecer, V., Maliar, T. and Miertus, S. (2000) Protease inhibitors as anticancer drugs role of molecular modelling and combinatorial chemistry in drug design. Int. J. Med. Biol. Environ. 28 161-173. 

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