Chromatin As A Target For The Dnabinding Anticancer Drugs

PARIJAT MAJUMDER, SUMAN K. PRADHAN, PUKHRAMBAM GRIHANJALI DEVI, SUDIPTA PAL AND DIPAK DASGUPTA*

Biophysics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-I, Bidhannagar, Kolkata - 700 064, India

Abstract: Chemotherapy has been a major approach to treat cancer. Both constituents of chromatin, chromosomal DNA and the associated chromosomal histone proteins are the molecular targets of the anticancer drugs. Small DNA binding ligands, which inhibit enzymatic processes with DNA substrate, are well known in cancer chemotherapy. These drugs inhibit the polymerase and topoisomerase activity. With the advent in the knowledge of chromatin chemistry and biology, attempts have shifted from studies of the structural basis of the association of these drugs or small ligands (with the potential of drugs) with DNA to their association with chromatin and nucleosome. These drugs often inhibit the expression of specific genes leading to a series of biochemical events. An overview will be given about the latest understanding of the molecular basis of their action. We shall restrict to those drugs, synthetic or natural, whose prime cellular targets are so far known to be chromosomal DNA

Keywords: Nucleosome, Chromosome, Intercalators, Groove-binders, DNA-cleaving agents, Cross-linkers, Chromatin condensation, Histone tails, Nucleosome phasing

The history of modern chemotherapy of cancer dates back to as early as 1946 when Goodman et al., 1946, produced the first report of clinical results from 67 patients treated with nitrogen mustards for Hodgkin's disease, lymphosarcoma, and leukemia. From then onwards, the search for newer and better anticancer agents has continued with an ever-increasing pace. Drugs designed vary not only in their sources, chemical compositions and modes of action, but also in their targets. Whereas certain anticancer drugs target nucleic acids, others target specific

* E-mail: [email protected]

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