Synthesis and biological studies of steroidal pyran based derivatives.

Abstract

Steroid based cancer chemotherapeutic agents of the type 2'-amino-3'-cyanocholest-6-eno[5,7-de]4H-pyrans (1c-3c) have been synthesized and characterized by the various spectroscopic and analytical techniques. The DNA binding studies of compounds (1c-3c) with CT DNA were carried out by UV-vis and fluorescence spectroscopy and gel electrophoresis. The compounds (1c-3c) bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb values found to be 5.4 × 10(3), 2.3 × 10(3)M(-1) and 1.97 × 10(3)M(-1), respectively indicating the higher binding affinity of compound (1c) towards DNA. The molecular docking study suggested that the electrostatic interaction of compounds (1c-3c) in between the nucleotide base pairs is due to the presence of pyran moiety in steroid molecule. All the compounds (1c-3c) cleave supercoiled pBR322 DNA via hydrolytic pathway, as validated by T4 DNA ligase assay. The compounds (1c-3c) were screened for in vitro cytotoxicity against the cancer and non-cancer cells SW480, A549, HepG2, HeLa, MCF-7, HL-60, DU-145, NL-20, HPC and HPLF by MTT assay. The compounds (1c-3c) were tested for genotoxicity (comet assay) involving apoptotic degradation of DNA and was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining. The results revealed that compound (1c) has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

• Authors: Shamsuzzaman, Ayaz Mahmood Dar, Yusuf Khan, Aamir Sohail
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 129 Pg. 36-47 (Dec 05 2013) ISSN: 1873-2682 [Electronic] Switzerland
• PMID: 24157729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• 2'-amino-3'-cyanocholest-6-eno(5,7-de)4H-pyran
• 3beta-acetoxy-2'-amino-3'-cyanocholest-6-eno(5,7-de)4H-pyran
• 3beta-choloro-2'-amino-3'-cyanocholest-6-eno(5,7-de)4H-pyran
• 4'-C-aminomethyl-2'-deoxy-2'-fluorouridine
• Antineoplastic Agents
• Cholestanes
• Pyrans
• Reactive Oxygen Species
• Steroids
• DNA
• Uridine

Topics

• Antineoplastic Agents (chemical synthesis, metabolism, toxicity)
• Apoptosis (drug effects)
• Binding Sites
• Cell Line, Tumor
• Cholestanes (chemical synthesis, metabolism, toxicity)
• Comet Assay
• DNA (chemistry, metabolism)
• DNA Cleavage (drug effects)
• HL-60 Cells
• HeLa Cells
• Hep G2 Cells
• Humans
• Hydrophobic and Hydrophilic Interactions
• MCF-7 Cells
• Molecular Docking Simulation
• Nucleic Acid Conformation
• Plasmids (chemistry, metabolism)
• Pyrans (chemical synthesis, chemistry, metabolism, toxicity)
• Reactive Oxygen Species (metabolism)
• Static Electricity
• Steroids (chemical synthesis, chemistry, toxicity)
• Uridine (analogs & derivatives, chemical synthesis, metabolism, toxicity)