title: Spectroscopic studies of the effects of anticancer drug mitoxantrone interaction with calf-thymus DNA.
abstract: Mitoxantrone (MTX) (1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione) is a synthetic antineoplastic drug, widely used as a potent chemotherapeutic agent in the treatment of various types of cancer. It is structurally similar to classical anthracyclines. Widespread interest in the anticancer agent mitoxantrone has arisen because of its apparent lower risk of cardio-toxic effects compared to the naturally occurring anthracyclines. In the present work, we investigated the interaction of mitoxantrone with DNA in the buffer solution at physiological pH using Fourier transform infrared (FTIR), UV-Visible absorption and circular dichroism spectroscopic techniques. FTIR analysis revealed the intercalation of mitoxantrone between the DNA base pairs along with its external binding with phosphate-sugar backbone. The binding constant calculated for mitoxantrone-DNA association was found to be 3.88×10(5)M(-1) indicating high affinity of drug with DNA double helix. Circular dichroism spectroscopic results suggest that there are no major conformational changes in DNA upon interaction with drug except some perturbations in native B-DNA at local level. The present work shows the capability of spectroscopic analysis to characterize the nature of drug-biomolecule complex and the effects of such interaction on the structure of biomolecule.
authors.affiliation: Quantum Optics and Photon Physics, CSIR-National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Agarwal
authors.forename: Deepak Kumar
authors.initials: DK
authors.lastname: Jangir
authors.forename: Ranjana
authors.initials: R
authors.lastname: Mehrotra
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D008942:Mitoxantrone / Q000378:metabolism* / Q000494:pharmacology*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D013057:Spectrum Analysis
chemical_list: D000970:Antineoplastic Agents; D004247:DNA; C427203:calf thymus DNA; D008942:Mitoxantrone