Synthesis of novel 3-(substituted phenyl) chromone derivatives and their anti-tumor activities / 第二军医大学学报

ABSTRACT

Objective: To search for new isoflavones with more potent antitumor activities from the target compounds synthesized by inserting a double bond or an acetylene bond between chromone and its 3-substituted phenyl, ester and hydroxymethyl groups, or by formation of an amide of 3′ or 4′-amino group of isoflavones with norcantharidin. Methods: The key intermediate 3-iodo-7-methoxyl-4H-chromen-4-one (5) was prepared with 2-hydroxyl-4-methoxyl- acetophenone and ethyl formate. The target compounds with 3-substituted double bond or acetylene groups were synthesized by Heck coupling and Sonogashira coupling reaction; the amide compounds were synthesized by Suzuki coupling reaction and amide formation of 3′ or 4′-amino group of isoflavones with norcantharidin. All of the target compounds were confirmed by 1HNMR, MS and IR spectra. The IC50 values of target compounds were determined by the standard method using two kinds of human tumor cell lines, colon cancer cell line HCT116 and liver cancer cell line SMMC 7721 to study their anti-tumor activities. Results: All the 17 target compounds obtained had certain anti-tumor effect in vitro, with compounds 7h and 7e showing better anti-tumor effects, which were similar to that of control curcumin and more potent than that of genistein in vitro. Conclusion: The insertion of a double bond or an acetylene bond between chromone and its 3-substituted phenyl, ester and hydroxymethyl groups may promote the anti-tumor activities of isoflavone analogues. It seems that the formation of an amide of 3′- or 4′-amino group of isoflavones with norcantharidin has no noticeable promotion effect on the anti-tumor activities.