Derivatization Studies With Anticancer Activity Monocarbonylation Curcumin Analogs

In order to ifnd some lead compounds with activities of anti-cancer, a total oftwo seires of72unreported compounds shown in the formula （I） and （II） weredesigned and synthesized.（1）For finding the leading compounds of anticancer drugs with high active,good selective, and low toxic, on the basis of previous work，we have focused ourattentions on derivatization of iV-（substitutedbenzyl）-3,5-bis（benzylidene）-4-Piperidones to gettetrahydropyrido[4,3-d]dihydropyrimidine-2-ones（thiones）(Ia₁-a_l6)),(Ib₁-b₂₄)) andtetrahydro-4//-pyrano[3,2-c](Ic₁-c_l6))，they can be synthesized with substitutedamines and methyl acrylate as raw mateirals via a seires of Michael addition,Dieckmann condensation, hydrolysis decarboxylation and Adol condensationreactions, then reacted with urea，thiorea，malononitrile，respectively,（2）With the purpose of reducing the toxicity of compounds （I crci6） to normalhematopoietic cells, a tumor targeting anti-CD14Monoclonal Antibody （McAb） wasused in conjugation with compounds (Ic₁-c_l6)) to get conjugates (Ic₁-c_l6))-Thestructural formulas of compounds are as follows respectively: All these unreported co’mpounds structures were confirmed by IR,!H NMR, MS,and elementary analysis. Moreover, their physic-chemical properties, spectrumproperties, reaction conditions were discussed as well.Further more, in order to investigate the relationship between the structure ofcompounds I and their properties, we nurtured and obtained the crystal structure ofcompound （I bio） by single crystal X-Ray diffraction analysis.The growth inhibition activities of the compounds (Ia₁-a_l6))，(Ib₁-b₂₄))，（ICi-C^） against leukemic K562cells, ovarian cancer H0-8910cells and liver cancerSMMC-7721cells proliferation were determined by the MTT assay according to thestandard bioactivity test procedures of the Zooblast-molecular Biology Laboratory ofShanghai Normal University of China. The results indicated that compounds(Ic₁-c_l6))have excellent apoptosis effects on K562cells.The preliminary toxicity tests of compounds (Ic₁-c_l6)) to normal hematopoieticcells were finished in Zooblast-molecular Biology Laboratory of Shanghai NormalUniversity of China. The inhibitory activity of compounds (Ic₁-c_l6)) toward K562cells were discovered to approach that of the compounds(Ic₁-c_l6)), but the toxicity ofconjugates (IIc₁-c_l6)) to normal hematopoietic cells declined obviously.