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

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

Design, synthesis and docking studies of novel spiroazetidinone substituted steroidal derivatives possessing potent diversified pharmacological properties

Steroidal spiroazetidinone derivatives (3, 10-12) were obtained by the multi-step reactions of ketosteroids. It involved Staudinger ketene-imine [2+2] cycloaddition reaction of steroidal iminophenylcholest-5-enes (2, 7-9). The structural assignment of the products was confirmed on the basis of IR, 1H NMR, 13C NMR, MS and analytical data. The synthesized compounds were screened for in vitro antimicrobial activity against different bacterial and fungal strains by agar diffusion method and in vitro antioxidant activity by using DPPH method. Docking studies were performed to investigate the hypothetical binding mode of the steroidal spiroazetidinones. The results suggest that steroidal bearing a core spiroazetidinone scaffold would be potent phramacological agents