Synthesis, characterization and in vitro anti-invasive activity screening of polyphenolic and heterocyclic compounds.

Abstract

Invasion is the hallmark of malignant tumors, and is responsible for the bad prognosis of the untreated cancer patients. The search for anti-invasive treatments led us to screen compounds of different classes for their effect in an assay for invasion. Thirty-nine new compounds synthesized in the present study along with 56 already reported compounds belonging mainly to the classes of lactones, pyrazoles, isoxazoles, coumarins, desoxybenzoins, aromatic ketones, chalcones, chromans, isoflavanones have been tested against organotypic confronting cultures of invasive human MCF-7/6 mammary carcinoma cells with embryonic chick heart fragments in vitro. Three of them (a pyrazole derivative, an isoxazolylcoumarin and a prenylated desoxybenzoin) inhibited invasion at concentrations as low as 1 microM; instead of occupying and replacing the heart tissue within 8 days, the MCF-7/6 cells grew around the heart fragments and left it intact, when treated with these compounds. At the anti-invasive concentration of 1 microM, the three compounds did not affect the growth of the MCF-7/6 cells, as shown in the sulforhodamine B assay. Aggregate formation on agar was not stimulated by any of the three anti-invasive compounds, making an effect on the E-cadherin/catenin complex improbable. This is an invasion suppressor that can be activated in MCF-7/6 cells by a number of other molecules. Our data indicate that some polyphenolic and heterocyclic compounds are anti-invasive without being cytotoxic for the cancer cells.

• Authors: Virinder S Parmar, Nawal K Sharma, Mofazzal Husain, Arthur C Watterson, Jayant Kumar, Lynne A Samuelson, Ashok L Cholli, Ashok K Prasad, Ajay Kumar, Sanjay Malhotra, Naresh Kumar, Amitabh Jha, Amarjit Singh, Ishwar Singh, Himanshu, Archana Vats, Najam A Shakil, Smriti Trikha, Shubasish Mukherjee, Sunil K Sharma, Sanjay K Singh, Ajay Kumar, Hriday N Jha, Carl E Olsen, Christophe P Stove, Marc E Bracke, Marc M Mareel
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 11 Issue 6 Pg. 913-29 (Mar 20 2003) ISSN: 0968-0896 [Print] England
• PMID: 12614877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Flavonoids
• Heterocyclic Compounds
• Indicators and Reagents
• Phenols
• Polyphenols

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Breast Neoplasms (pathology)
• Cell Aggregation
• Cell Division (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Flavonoids (chemical synthesis, chemistry, pharmacology)
• Heterocyclic Compounds (chemical synthesis, chemistry, pharmacology)
• Humans
• Indicators and Reagents
• Magnetic Resonance Spectroscopy
• Neoplasm Invasiveness (pathology)
• Phenols (chemical synthesis, chemistry, pharmacology)
• Polyphenols
• Structure-Activity Relationship
• Tumor Cells, Cultured