US EPA

4923443 

Journal Article 

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

Dar, AM; Rah, B; Mir, S; Nabi, R; Shamsuzzaman, R; Gatoo, MA; Mashrai, A; Khan, Y 

2018 

Yes 

International Journal of Biological Macromolecules
ISSN: 0141-8130
EISSN: 1879-0003 

111 

52-61 

English 

29292141 

10.1016/j.ijbiomac.2017.12.128 

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; 2.31×103M-1, 1.93×103M-1 and 2.05×103M-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. 

Index Medicus