title: DNA binders in clinical trials and chemotherapy.
abstract: Cancer has always been a dreadful disease and continues to attract extensive research investigations. Various targets have been identified to restrain cancer. Among these DNA happens to be the most explored one. A wide variety of small molecules, often referred to as 'ligands', has been synthesized to target numerous structural features of DNA. The sole purpose of such molecular design has been to interfere with the transcriptional machinery in order to drive the cancer cell toward apoptosis. The mode of action of the DNA targeting ligands focuses either on the sequence-specificity by groove binding and strand cleavage, or by identifying the morphologically distinct higher order structures like that of the G-quadruplex DNA. However, in spite of the extensive research, only a tiny fraction of the molecules have been able to reach clinical trials and only a handful are used in chemotherapy. This review attempts to record the journey of the DNA binding small molecules from its inception to cancer therapy via various modifications at the molecular level. Nevertheless, factors like limited bioavailability, severe toxicities, unfavorable pharmacokinetics etc. still prove to be the major impediments in the field which warrant considerable scope for further research investigations.
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Asfa
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India; Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560 064, India. Electronic address: sb@orgchem.iisc.ernet.in.
authors.forename: Santanu
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002986:Clinical Trials as Topic; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands
chemical_list: D004273:DNA, Neoplasm; D008024:Ligands
keywords: Anticancer; Chemotherapy; Clinical trials; DNA binders; Duplex DNA; G-quadruplex DNA; Topoisomerase