PMID- 34740600 OWN - NLM STAT- MEDLINE DCOM- 20220103 LR - 20220103 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 351 DP - 2022 Jan 5 TI - A new arylsulfanyl-benzo-2,1,3-thiadiazoles derivative produces an anti-amnesic effect in mice by modulating acetylcholinesterase activity. PG - 109736 LID - S0009-2797(21)00374-4 [pii] LID - 10.1016/j.cbi.2021.109736 [doi] AB - The aim of the present study was investigate the binding affinity of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5]thiadiazole (MTDZ) with acetylcholinesterase (AChE). We also evaluated the effect of MTDZ against scopolamine (SCO)-induced amnesia in mice and we looked at the toxicological potential of this compound in mice. The binding affinity of MTDZ with AChE was investigated by molecular docking analyses. For an experimental model, male Swiss mice were treated daily with MTDZ (10 mg/kg, intragastrically (i.g.)) or canola oil (10 ml/kg, i.g.), and induced, 30 min later, with injection of SCO (0.4 mg/kg, intraperitoneally (i.p.)) or saline (0.9%, 5 ml/kg, i.p.) daily. From day 1 to day 10, mice were submitted to the behavioral tasks (Barnes maze, open-field, object recognition and location, Y-maze and step-down inhibitory avoidance tasks), 30 min after induction with SCO. On the tenth day, the animals were euthanized and blood was collected for the analysis of biochemical markers (creatinine, aspartate (AST), and alanine (ALT) aminotransferase). MTDZ interacts with residues of the AChE active site. SCO caused amnesia in mice by changing behavioral tasks. MTDZ treatment attenuated the behavioral changes caused by SCO. In ex vivo assay, MTDZ also protected against the alteration of AChE activity, reactive species (RS) levels, thiobarbituric acid reative species (TBARS) levels, catalase (CAT) activity in tissues, as well as in transaminase activities of plasma caused by SCO in mice. In conclusion, MTDZ presented anti-amnesic action through modulation of the cholinergic system and provided protection from kidney and liver damage caused by SCO. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - da Costa Rodrigues, Karline AU - da Costa Rodrigues K AD - Postgraduate Program in Biochemistry and Bioprospecting, Research Laboratory in Biochemical Pharmacology (LaFarBio), Research Group in Neurobiotechnology (GPN), Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas (UFPel), CEP 96010- 900, Pelotas, RS, Brazil. FAU - Leivas de Oliveira, Renata AU - Leivas de Oliveira R AD - Postgraduate Program in Biochemistry and Bioprospecting, Research Laboratory in Biochemical Pharmacology (LaFarBio), Research Group in Neurobiotechnology (GPN), Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas (UFPel), CEP 96010- 900, Pelotas, RS, Brazil. FAU - da Silva Chaves, Julia AU - da Silva Chaves J AD - Postgraduate Program in Biochemistry and Bioprospecting, Research Laboratory in Biochemical Pharmacology (LaFarBio), Research Group in Neurobiotechnology (GPN), Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas (UFPel), CEP 96010- 900, Pelotas, RS, Brazil. FAU - Esteves da Rocha, Vanessa Macedo AU - Esteves da Rocha VM AD - Postgraduate Program in Biochemistry and Bioprospecting, Research Laboratory in Biochemical Pharmacology (LaFarBio), Research Group in Neurobiotechnology (GPN), Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas (UFPel), CEP 96010- 900, Pelotas, RS, Brazil. FAU - Fuzinato Dos Santos, Beatriz AU - Fuzinato Dos Santos B AD - Laboratory of Organic Catalysis and Biocatalysis, Federal University of Grande Dourados (UFGD), 79825-070, Dourados, MS, Brazil. FAU - Fronza, Mariana Gallio AU - Fronza MG AD - Postgraduate Program in Biotechnology, GPN, Technological Development Center, UFPel, CEP, 96010-900, Pelotas, RS, Brazil. FAU - Luis de Campos Domingues, Nelson AU - Luis de Campos Domingues N AD - Laboratory of Organic Catalysis and Biocatalysis, Federal University of Grande Dourados (UFGD), 79825-070, Dourados, MS, Brazil. FAU - Savegnago, Lucielli AU - Savegnago L AD - Postgraduate Program in Biotechnology, GPN, Technological Development Center, UFPel, CEP, 96010-900, Pelotas, RS, Brazil. FAU - Wilhelm, Ethel Antunes AU - Wilhelm EA AD - Postgraduate Program in Biochemistry and Bioprospecting, Research Laboratory in Biochemical Pharmacology (LaFarBio), Research Group in Neurobiotechnology (GPN), Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas (UFPel), CEP 96010- 900, Pelotas, RS, Brazil. Electronic address: ethel.wilhelm@ufpel.edu.br. FAU - Luchese, Cristiane AU - Luchese C AD - Postgraduate Program in Biochemistry and Bioprospecting, Research Laboratory in Biochemical Pharmacology (LaFarBio), Research Group in Neurobiotechnology (GPN), Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas (UFPel), CEP 96010- 900, Pelotas, RS, Brazil. Electronic address: cristiane.luchese@ufpel.edu.br. LA - eng PT - Journal Article DEP - 20211103 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 0 (Cholinesterase Inhibitors) RN - 0 (Nootropic Agents) RN - 0 (Sulfides) RN - 0 (Thiadiazoles) RN - DL48G20X8X (Scopolamine) RN - EC 3.1.1.7 (Acetylcholinesterase) SB - IM MH - Acetylcholinesterase/*metabolism MH - Amnesia/chemically induced/*drug therapy MH - Animals MH - Avoidance Learning/drug effects MH - Cholinesterase Inhibitors/metabolism/*therapeutic use MH - Male MH - Maze Learning/drug effects MH - Mice MH - Molecular Docking Simulation MH - Nootropic Agents/metabolism/*therapeutic use MH - Protein Binding MH - Scopolamine MH - Sulfides/metabolism/*therapeutic use MH - Thiadiazoles/metabolism/*therapeutic use OTO - NOTNLM OT - Acetylcholinesterase OT - Amnesia OT - Anti-amnesic OT - Dementia OT - Thiadiazoles EDAT- 2021/11/07 06:00 MHDA- 2022/01/04 06:00 CRDT- 2021/11/06 05:31 PHST- 2021/06/25 00:00 [received] PHST- 2021/10/20 00:00 [revised] PHST- 2021/11/01 00:00 [accepted] PHST- 2021/11/07 06:00 [pubmed] PHST- 2022/01/04 06:00 [medline] PHST- 2021/11/06 05:31 [entrez] AID - S0009-2797(21)00374-4 [pii] AID - 10.1016/j.cbi.2021.109736 [doi] PST - ppublish SO - Chem Biol Interact. 2022 Jan 5;351:109736. doi: 10.1016/j.cbi.2021.109736. Epub 2021 Nov 3.