Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents

• Published in: Molecules (Basel, Switzerland) Vol. 21; no. 11; p. 1598
• Main Authors: Altıntop, Mehlika Dilek, Temel, Halide Edip, Sever, Belgin, Akalın Çiftçi, Gülşen, Kaplancıklı, Zafer Asım
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-11-2016; MDPI
• Subjects: A549 Cells; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; benzodioxole; Benzodioxoles - chemistry; Cancer; Cell division; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - pharmacology; docking studies; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Enzymes; Humans; Investigations; Membrane Potential, Mitochondrial - drug effects; Mice; mitochondrial membrane potential; Molecular Docking Simulation; Molecular Structure; NIH 3T3 Cells; Pharmacy; Rats; Ribonucleotide reductase; SIRT1; Structure-Activity Relationship; thiosemicarbazone; Thiosemicarbazones - chemical synthesis; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology; Toxicity; Tumorigenesis; Turkey; benzodioxole; docking studies; mitochondrial membrane potential; thiosemicarbazone; apoptosis; cancer; SIRT1
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21111598

New benzodioxole-based thiosemicarbazone derivatives were synthesized and evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the correlation between anticancer activity and cholinesterases, the compounds were evaluated for their inhibitory effects on AChE and BuChE. The most effective anticancer agents were investigated for their effects on DNA synthesis, apoptosis and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1'-biphenyl]-4-ylmethylene)thiosemicarbazide (
) was identified as the most promising anticancer agent against C6 and A549 cell lines due to its inhibitory effects on C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound
increased early and late apoptosis in A549 and C6 cells. Compound
also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound
was investigated for SIRT1 inhibitory activity to provide mechanistic insight and for that purpose docking studies were also performed for this compound on SIRT1. On the other hand, compound
did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound
and cholinesterases.