Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα

Abstract

Phenotypic screening of α-substituted thiocarbohydrazones revealed promising activity of 1,5-bis(salicylidene)thiocarbohydrazide against leukemia and breast cancer cells. Supplementary cell-based studies indicated an impairment of DNA replication via the ROS-independent pathway. The structural similarity of α-substituted thiocarbohydrazone to previously published thiosemicarbazone catalytic inhibitors targeting the ATP-binding site of human DNA topoisomerase IIα prompted us to investigate the inhibition activity on this target. Thiocarbohydrazone acted as a catalytic inhibitor and did not intercalate the DNA molecule, which validated their engagement with this cancer target. A comprehensive computational assessment of molecular recognition for a selected thiosemicarbazone and thiocarbohydrazone provided useful information for further optimization of this discovered lead compound for chemotherapeutic anticancer drug discovery.

Antioxidant Properties of Biodiesel-Diesel Blends and Non-Isothermal Kinetic Studies of Schiff-Based Isatin-Thiosemicarbazone Derivatives

“…Thiosemicarbazones are a notable category of synthetic chemicals that exhibit a diverse range of pharmacological and biological activities [21]. A diverse range of actions have been disclosed, including anti-HIV [22], anticancer [23], antimalarial [24], anticonvulsant [25], antiinflammatory [26], antioxidant [27], anti-viral [28], enzymatic inhibition [29], antifungal [30], and antibacterial [31] properties. Isatin derivatives have demonstrated a wide range of biological activities, including antioxidant [32], antiviral [33], antifungal [34], antibacterial [35], antimicrobial [36], anti-HIV [22], antitubercular [37], and anticonvulsant [38] properties.…”

The Investigation of the Synthesis, Characterization, Molecular Docking, and Pharmacokinetic Properties of New Thiocarbohydrazones Based on Schiff Bases

“…These compounds exhibit a range of beneficial effects, including their ability to prevent cancer [27,28], DNA repair [28], fight against microbes [29], kill bacteria [24], combat fungal infections [29], act as antioxidants [30], destroy cells [31], inhibit viruses [32], suppress tumor growth [13], and protect against corrosion [33]. Both isatin-based thiocarbohydrazone and Schiff bases possess pharmacological and biological characteristics [34].…”