title: 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.affiliation: Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi-110 007, India. virparmar@yahoo.co.in
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Nawal K
authors.initials: NK
authors.lastname: Sharma
authors.forename: Mofazzal
authors.initials: M
authors.lastname: Husain
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Watterson
authors.forename: Jayant
authors.initials: J
authors.lastname: Kumar
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Samuelson
authors.forename: Ashok L
authors.initials: AL
authors.lastname: Cholli
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.forename: Sanjay
authors.initials: S
authors.lastname: Malhotra
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
authors.forename: Amitabh
authors.initials: A
authors.lastname: Jha
authors.forename: Amarjit
authors.initials: A
authors.lastname: Singh
authors.forename: Ishwar
authors.initials: I
authors.lastname: Singh
authors.lastname: Himanshu
authors.forename: Archana
authors.initials: A
authors.lastname: Vats
authors.forename: Najam A
authors.initials: NA
authors.lastname: Shakil
authors.forename: Smriti
authors.initials: S
authors.lastname: Trikha
authors.forename: Shubasish
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Singh
authors.forename: Ajay
authors.initials: A
authors.lastname: Kumar
authors.forename: Hriday N
authors.initials: HN
authors.lastname: Jha
authors.forename: Carl E
authors.initials: CE
authors.lastname: Olsen
authors.forename: Christophe P
authors.initials: CP
authors.lastname: Stove
authors.forename: Marc E
authors.initials: ME
authors.lastname: Bracke
authors.forename: Marc M
authors.initials: MM
authors.lastname: Mareel
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002449:Cell Aggregation; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009361:Neoplasm Invasiveness / Q000473:pathology*; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D010636:Phenols; D059808:Polyphenols