Structural studies on bioactive compounds. 40.(1) Synthesis and biological properties of fluoro-, methoxyl-, and amino-substituted 3-phenyl-4H-1-benzopyran-4-ones and a comparison of their antitumor activities with the activities of related 2-phenylbenzothiazoles.
A new series of fluoro-, methoxyl-, and amino-substituted isoflavones have been synthesized as potential antitumor agents based on structural similarities to known flavones and isoflavones (quercetin and genistein respectively) and antitumor 2-phenylbenzothiazoles. Target compounds were synthesized using palladium-catalyzed coupling methodologies to construct the central aryl carbon-carbon single bond. The new isoflavone derivatives were tested for in vitro activity in human breast (MDA-MB-468 and MCF-7) and colon (HT29 and HCT-116) cancer cell lines. Low micromolar GI50 values were obtained in a number of cases, with the MDA-MB-468 cell line being the most sensitive overall. Notably, significant potentiation of growth inhibitory activity (GI50<1 microM for 12d, 12f, 12h, 12k, 12l, 12o but not the methylene-bridged derivative 12i) was observed when MDA-MB-468 cells were co-incubated with TBDD, a powerful inducer of cytochrome P450 (CYP)-1A1 activity, suggesting that isoflavone derivatives can act as substrates for CYP1A1 bioactivation.
Vasselin
David A
DA
Cancer Research UK Experimental Cancer Chemotherapy Research Group, Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
Westwell
Andrew D
AD
Matthews
Charles S
CS
Bradshaw
Tracey D
TD
Stevens
Malcolm F G
MF
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002867:Chromones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D002867:Chromones; D013844:Thiazoles