title: Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives as Potential Antitumor Agents.
abstract: 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 (5) 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. Compound5increased early and late apoptosis in A549 and C6 cells. Compound5also caused disturbance on mitochondrial membrane potential and showed DNA synthesis inhibitory activity in A549 and C6 cells. Compound5was 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, compound5did not show any inhibitory activity against AChE and BuChE. This outcome pointed out that there is no relationship between anticancer activity of compound5and cholinesterases.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. mdaltintop@anadolu.edu.tr.
authors.forename: Mehlika Dilek
authors.initials: MD
authors.lastname: Altıntop
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. heincedal@anadolu.edu.tr.
authors.forename: Halide Edip
authors.initials: HE
authors.lastname: Temel
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. belginsever@anadolu.edu.tr.
authors.forename: Belgin
authors.initials: B
authors.lastname: Sever
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. gakalin@anadolu.edu.tr.
authors.forename: Gülşen
authors.initials: G
authors.lastname: Akalın Çiftçi
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. zakaplan@anadolu.edu.tr.
authors.forename: Zafer Asım
authors.initials: ZA
authors.lastname: Kaplancıklı
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052117:Benzodioxoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D051381:Rats; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D002800:Cholinesterase Inhibitors; D013882:Thiosemicarbazones
keywords: SIRT1; apoptosis; benzodioxole; cancer; docking studies; mitochondrial membrane potential; thiosemicarbazone