Interaction of two anticancer drugs (Epirubicin hydrochloride and Mitoxantron hydrochloride) with ct-DNA: Circular dichroism and molecular modeling techniques
- سال انتشار: 1397
- محل انتشار: سومین کنگره بین المللی پزشکی شخصی ایران
- کد COI اختصاصی: IPMCMED03_038
- زبان مقاله: انگلیسی
- تعداد مشاهده: 495
نویسندگان
۱Department of Biology, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran
چکیده
The binding interaction of Epirubicin hydrochloride and Mitoxantron hydrochloride with calf thymus DNA (ct-DNA) was studied using circular dichroism (CD). The CD spectroscopy is a powerful way in determining the secondary structure changes of DNA after binding with small molecules and has widely been used to investigate the interaction between small molecules and DNA. The CD spectra of ct-DNA in Tris-HCl buffer solution in the absence and presence of increasing concentrations of two drugs Epirubicin hydrochloride and Mitoxantron hydrochloride were recorded and when were added to the ct-DNA solution, the changes of CD spectrum of ct-DNA had slightly changed due to the binding interaction between Epirubicin hydrochloride and Mitoxantron hydrochloride with ct-DNA. This evidence supports intercalative binding of Epirubicin hydrochloride-DNA and Mitoxantron hydrochloride-DNA interactions. From molecular modeling methods, a docked structure with minimum energy was obtained in which Epirubicin hydrochloride and Mitoxantron hydrochloride were located in intercalation mode of ct-DNA. Introduction: Investigation of drug-DNA interaction is important for understanding the drug action at molecular level and for designing specific DNA target drug. Mioxantron hydrochloride 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 anthracylines. Also Epirubicin hydrochloride used for treatment of breast cancer. Methods: Calf thymus DNA, Mitoxantron hydrochloride, Epirubicin hydrochloride were purchased from sigma Aldrich corporation (St. Louis, Mo, USA). CD spectra were recorded with a Jasco-810 spectropolarimeter (Jasco, Japan).Results: The increase of the negative peak intensity near (250 nm) showed that the interaction of Epirubicin hydrochloride and Mitoxantron hydrochloride with ct-DNA made the double helix structure of ct-DNA become tight. The decrease of the positive band intensity near (280 nm) showed that base stacking band changes.Conclusion: This evidence supports intercalative binding of Epirubicin hydrochloride-DNA and Mitoxantron hydrochloride-DNA interactions. From molecular modeling methods, a docked structure with minimum energy was obtained in which Epirubicin hydrochloride and Mitoxantron hydrochloride were located in intercalation mode of ct-DNA.کلیدواژه ها
Epirubicin hydrochloride, calf thymus DNA (ct-DNA), Mitoxantron hydrochloride, Circular dichroism (CD), molecular modelingمقالات مرتبط جدید
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