Chromatin as a target for the DNA-binding anticancer drugs.
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.
Majumder
Parijat
P
Biophysics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-I, Bidhannagar, Kolkata-700 064, India.
Pradhan
Suman K
SK
Devi
Pukhrambam Grihanjali
PG
Pal
Sudipta
S
Dasgupta
Dipak
D
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003461:Crystallography; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D045566:DNA, Cruciform / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D054856:G-Quadruplexes; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007364:Intercalating Agents / Q000494:pharmacology; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D019384:Nucleic Acid Synthesis Inhibitors; D013816:Thermodynamics; D059003:Topoisomerase Inhibitors
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D002843:Chromatin; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D045566:DNA, Cruciform; D004791:Enzyme Inhibitors; D007364:Intercalating Agents; D019384:Nucleic Acid Synthesis Inhibitors; D059003:Topoisomerase Inhibitors; C051802:triplex DNA; D004247:DNA; D015254:DNA Modification Methylases