DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines
| Autor: | Rizwan Nabi, Shamsuzzaman, Ayaz Mahmood Dar, Manzoor Ahmad Gatoo, Ashraf Mashrai, Shafia Mir, Bilal Rah, Yusuf Khan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
RUTHENIUM(II) COMPLEXES Apoptosis 01 natural sciences Biochemistry Western blotting CONDENSATION chemistry.chemical_compound Structural Biology CALF THYMUS DNA MIT assay DOCKING Gel electrophoresis biology DERIVATIVES Chemistry General Medicine 3. Good health Molecular Docking Simulation Blot ACID MCF-7 Cells Steroids LIGANDS Thiosemicarbazones Pyrimidine UV-vis Antineoplastic Agents 010402 general chemistry Fluorescence 03 medical and health sciences Humans MTT assay Binding site Molecular Biology Cell Proliferation Nuclease Binding Sites 030102 biochemistry & molecular biology CLEAVAGE DNA Malonates 0104 chemical sciences STRAND Pyrimidines Docking (molecular) biology.protein |
| Zdroj: | International Journal of Biological Macromolecules. 111:52-61 |
| ISSN: | 0141-8130 |
| Popis: | The new steroidal pyrimidine derivatives (4-6) were synthesized by the reaction of steroidal thiosemicarbazones with (2-methyl) diethyl malonate in absolute ethanol. After characterization by spectral and analytical data, the DNA interaction studies of compounds (4-6) were carried out by UV-vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with K-b; 2.31 x 10(3) M-1, 1.93 x 10(3) M-1 and 2.05 x 10(3) M-1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed a strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of steroidal pyrimidine moiety in the minor groove of DNA. During in vitro cytotoxicity, compounds (4-6) revealed potential toxicity against the different human cancer cells (MTT assay). During DAPI staining, the nuclear fragmentations on cells occurred after treatment with compounds 4 and 5. Western blotting analysis clearly indicates that compound 4 causes apoptosis in MCF-7 cancer cells. The results revealed that compound 4 has better prospectus to act as a cancer chemotherapeutic candidate, which warrants further in vivo anticancer investigations. (C) 2017 Published by Elsevier B.V. |
| Databáze: | OpenAIRE |
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