title: A theoretical study on interactions between mitoxantrone as an anticancer drug and DNA: application in drug design.
abstract: This research is an effort to further understand the physicochemical interaction between the novel drug, mitoxantrone (MTX) and its biologic receptor, DNA. The ultimate goal is to design drugs that interact more with DNA. Understanding the physicochemical properties of the drug as well as the mechanism by which it interacts with DNA, it should ultimately allow the rational design of novel anti-cancer or anti-viral drugs. Molecular modelling on the complex formed between MTX and DNA presented that this complex was indeed fully capable of participating in the formation of a stable intercalation site. Furthermore, the molecular geometries of MTX and the DNA bases (adenine, guanine, cytosine and thymine) were optimized with the aid of the B3LYP/6-31G* method. The properties of the isolated intercalator and its stacking interactions with the adenine...thymine (AT) and guanine...cytosine (GC) nucleic acid base pairs were studied with the DFTB method (density functional tight-binding), an approximate version of the DFT method, that was extended to cover the London dispersion energy. The B3LYP/6-31G* stabilization energies of the intercalator...base pair complexes were found 10.06 kcal/mol and 21.64 kcal/mol for AT...MTX and GC...MTX, respectively. It was concluded that the dispersion energy and the electrostatic interaction contributed to the stability of the intercalator.DNA base pair complexes. The results concluded from the comparison of the DFTB method and the Hartree-fock method point out that these methods show close results and support each other.
authors.affiliation: Institute of Petroleum Engineering, Faculty of Engineering, University of Tehran, Tehran, IranCenter of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, P. O. Box 14155-6455, Tehran, IranMedical Nanotechnology Research Centre, Medical Sciences/University of Tehran, Tehran, P.O. Box 14155-6451, Iran.
authors.forename: Siavash
authors.initials: S
authors.lastname: Riahi
authors.affiliation: Institute of Petroleum Engineering, Faculty of Engineering, University of Tehran, Tehran, IranCenter of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, P. O. Box 14155-6455, Tehran, IranMedical Nanotechnology Research Centre, Medical Sciences/University of Tehran, Tehran, P.O. Box 14155-6451, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Reza Ganjali
authors.affiliation: Institute of Petroleum Engineering, Faculty of Engineering, University of Tehran, Tehran, IranCenter of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, P. O. Box 14155-6455, Tehran, IranMedical Nanotechnology Research Centre, Medical Sciences/University of Tehran, Tehran, P.O. Box 14155-6451, Iran.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
authors.affiliation: Institute of Petroleum Engineering, Faculty of Engineering, University of Tehran, Tehran, IranCenter of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, P. O. Box 14155-6455, Tehran, IranMedical Nanotechnology Research Centre, Medical Sciences/University of Tehran, Tehran, P.O. Box 14155-6451, Iran.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Karamdoust
authors.affiliation: Institute of Petroleum Engineering, Faculty of Engineering, University of Tehran, Tehran, IranCenter of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, P. O. Box 14155-6455, Tehran, IranMedical Nanotechnology Research Centre, Medical Sciences/University of Tehran, Tehran, P.O. Box 14155-6451, Iran.
authors.forename: Kowsar
authors.initials: K
authors.lastname: Bagherzadeh
authors.affiliation: Institute of Petroleum Engineering, Faculty of Engineering, University of Tehran, Tehran, IranCenter of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, P. O. Box 14155-6455, Tehran, IranMedical Nanotechnology Research Centre, Medical Sciences/University of Tehran, Tehran, P.O. Box 14155-6451, Iran.
authors.forename: Parviz
authors.initials: P
authors.lastname: Norouzi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D020029:Base Pairing; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007364:Intercalating Agents; D008942:Mitoxantrone / Q000737:chemistry*; D008958:Models, Molecular; D055672:Static Electricity
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D004247:DNA; D008942:Mitoxantrone