Studies On The Synthesis And Bioactivity Of5,6-disubstituted-2,3-pyridinedione Thiosemicarbazone Derivatives

The thiosemicarbazone compounds have already become the focus point of thepharmaceutical industry, the pesticide industry and the chemical industry, due to their goodpharmacological and biological activity. These compounds exhibit good biological activities,such as anti-bacterial, anti-viral property, anti-neoplastic, anti-tuberculosis, anti-malarial,anti-leprosy, anti-parasites and so on, which are widely used in medical research.Thesecompounds were got enough attention from the pesticide industry, as they have the activity ofanti-boll rot of cotton,anti-rhizoctonia rot of cotton, anti-fusarium wilt, anti-botrytis cinerea ofwheat and they are capable of regulating of the plant growth activity. The thiosemicarbazonehas N, S and the radical of C=N, so they are also an important class of intermediatecompounds in the synthesis of the organic chemistry. A new series of5,6-disubstituted-2,3-pyridine-diones thiosemicarbazone derivatives and a new series of3-（3-sulfydrylphenmethyl）-5,6-disubstituted-2,3-pyridinedione thiosemicarbazone weresynthesized.14novel5,6-disubstituted-2,3-pyridinedione thiosemicarbazone and7novel3-（3-sulfydrylphenmethyl）-5,6-disubstituted-2,3-pyridine-diones thiosemicarbazone wereprepared under the efficient synthesis conditions. Their structures were characterized by IR,¹H NMR,¹³C NMR, MS. The anti-cancer activity of novel5,6-di substituted-2,3-pyridine-diones thiosemicarbazone were assayed, and the results showed some compounds exhibitedgood anti-cancer activity. The main results are shown as follows:1.14novel of5,6-disubstituted-2,3-pyridinedione compounds were prepared according tothe literature method, their structures were characterized by IR, m.p. The results just like thereport of the literature.2.5,6-disubstituted-2,3-pyridinedione compounds were synthesized by5,6-disubstituted-2,3-pyridinedione and thiosemicarbazide under the acidity condition, The optimum synthesisconditions were obtained:the molar ratio of reactants being1:1.4, the amount of concentratedsulfuric acid being3drops, reaction time being4.5hours,the reaction temperature being65℃.3.Due to the tautomerism of5,6-disubstituted-2,3-pyridinedion thiosemicarbazone,weplaned to use benzyl bromide protecting hydrosulphonyl,in order to remove the tautomerism.3-（3-sulfydrylphenmethyl）-5,6-disubstituted-2,3-pyridine-diones thiosemicarbazone weresynthesized by5,6-disubstituted-2,3-pyridinedione thiosemicarbaz one and benzyl bromide under basis condition. The optimum synthesis conditions were obtained:the molar ratio ofreactants being1:1.2:2.5, the reaction temperature being50℃, reaction time being35min.4. The antitumor activity of novel5,6-disubstituted-2,3-pyridinedione ompounds wereassayed, and the results showed some compounds exhibited good activity against breastcancerMCF-7, rectal cancer HCT116, liver cancer7332.