Synthesis and antiproliferative activity of benzophenone tagged pyridine analogues towards activation of caspase activated DNase mediated nuclear fragmentation in Dalton's lymphoma.

Abstract

A series of benzophenones possessing pyridine nucleus 8a-l were synthesized by multistep reaction sequence and evaluated for antiproliferative activity against DLA cells by in vitro and in vivo studies. The results suggested that, compounds 8b with fluoro group and 8e with chloro substituent at the benzoyl ring of benzophenone scaffold as well as pyridine ring with hydroxy group exhibited significant activity. Further investigation in mouse model suggests that compounds 8b and 8e have the potency to activate caspase activated DNase (endonuclease) which is responsible for DNA fragmentation, a primary hallmark of apoptosis and thereby inhibits the Dalton's lymphoma ascites tumour growth.

• Authors: Mohammed Al-Ghorbani, Prabhu Thirusangu, H D Gurupadaswamy, V Girish, H G Shamanth Neralagundi, B T Prabhakar, Shaukath Ara Khanum
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 65 Pg. 73-81 (Apr 2016) ISSN: 1090-2120 [Electronic] United States
• PMID: 26874345 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Benzophenones
• Pyridines
• benzophenone
• Deoxyribonucleases
• Caspases
• pyridine

Topics

• Animals
• Benzophenones (chemical synthesis, chemistry, pharmacology)
• Caspases (metabolism)
• Cell Nucleus (drug effects, enzymology, pathology)
• Cell Proliferation (drug effects)
• DNA Fragmentation (drug effects)
• Deoxyribonucleases (metabolism)
• Enzyme Activation (drug effects)
• Female
• Humans
• Lymphoma (genetics, pathology)
• Mice
• Molecular Structure
• Neoplasms, Experimental (drug therapy, pathology)
• Pyridines (chemical synthesis, chemistry, pharmacology)
• Tumor Cells, Cultured