DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines

Dar, A.M and Rah, B. and Mir, S. and Nabi, R. and Shamsuzzaman, . and Gatoo, M.A and Mashrai, A and Khan, Y. (2018) DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines. International Journal of Biological Macromolecules, 111. pp. 52-61. ISSN 1418130

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Official URL: http://www.sciencedirect.com/science/article/pii/S...


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 Kb; 2.31 × 103 M− 1, 1.93 × 103 M− 1 and 2.05 × 103 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.

Item Type: Article
Uncontrolled Keywords: Fluorescence; MTT assay; Pyrimidine; UV–vis; Western blotting
Subjects: Q Science > QD Chemistry
Divisions: Faculties > Faculty of Science > Department of Chemistry
Depositing User: AMU Library
Date Deposited: 19 Jan 2018 05:20
Last Modified: 19 Jan 2018 05:20
URI: http://ir.amu.ac.in/id/eprint/10828

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