pyridoxal-thiosemicarbazone and Neoplasms

Topoisomerase (Topo) accelerates cell growth and division, and has been a theoretical 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 intermolecular forces. The combination of PLT derivatives and copper gluconate (CuGlu) improved their anti-tumour activity against a cell line with high expression of topoisomerase (SK-BR-3). The non-linear regression equations of the inhibitory activity and anti-tumour activity of Topo-I and Topo-IIɑ in SK-BR-3 cells had R

Topics: Antineoplastic Agents; Cell Division; Copper; DNA Topoisomerases, Type II; Humans; Ions; Ligands; Neoplasms; Pyridoxal; Thiosemicarbazones; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors