Pyridoxal hydrochloride thiosemicarbazones with copper ions inhibit cell division via Topo-I and Topo-II was written by Qi, Jinxu;Zheng, Yunyun;Li, Bin;Ai, Yu;Chen, Mengyao;Zheng, Xinhua. And the article was included in Journal of Inorganic Biochemistry in 2022.Synthetic Route of C8H10ClNO3 The following contents are mentioned in the article:
Topoisomerase (Topo) accelerates cell growth and division, and has been a theor. target for anti-cancer drugs for decades. A series of pyridoxal thiosemicarbazone (PLT) ligands were designed and synthesized, and the dependence of their antiproliferative activity on copper was investigated. The insertion of N-cyclohexyl-2-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)-N-methylhydrazinecarbothioamide hydrochloride (compound 9) and Chlorido(N-cyclohexyl-2-((3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)methylene)-N-methylhydrazinecarbothioamide hydrochloride-O,N,S)-copper(II) nitrate (9-Cu complex) into Topo-I and Topo-II prevented uncoiling of DNA through hydrogen bonds and intermol. forces. The combination of PLT derivatives and copper gluconate (CuGlu) improved their anti-tumor activity against a cell line with high expression of topoisomerase (SK-BR-3). The non-linear regression equations of the inhibitory activity and anti-tumor activity of Topo-I and Topo-II in SK-BR-3 cells had R2 values of 0.93 and 0.94, resp. In addition to lipophilicity, inhibition of topoisomerase also affected the activity of PLT ligands by coordinating with copper ions. At the cellular level, PLTs and CuGlu penetrate the cell membrane to form metabolites in the cell, thus selectively inhibiting the activity of Topo-I and Topo-II, and ultimately inhibiting cell division. These findings will inform the design of future anti-cancer thiosemicarbazone drugs. This study involved multiple reactions and reactants, such as 3-Hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde hydrochloride (cas: 65-22-5Synthetic Route of C8H10ClNO3).
3-Hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde hydrochloride (cas: 65-22-5) belongs to alcohols. Alkyl halides are often synthesized from alcohols, in effect substituting a halogen atom for the hydroxyl group. Secondary alcohols are easily oxidized without breaking carbon-carbon bonds only as far as the ketone stage. No further oxidation is seen except under very stringent conditions.Synthetic Route of C8H10ClNO3
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