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Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors.
Bioorg Med Chem. 2013 Apr 01; 21(7):1735-48.BM

Abstract

A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, (1)H, (13)C and (19)F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound.

Authors+Show Affiliations

Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ-532 10 Pardubice, Czech Republic. Ales.Imramovsky@upce.czNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23462716

Citation

Imramovský, Aleš, et al. "Synthesis and in Vitro Evaluation of New Derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as Cholinesterase Inhibitors." Bioorganic & Medicinal Chemistry, vol. 21, no. 7, 2013, pp. 1735-48.
Imramovský A, Pejchal V, Štěpánková Š, et al. Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors. Bioorg Med Chem. 2013;21(7):1735-48.
Imramovský, A., Pejchal, V., Štěpánková, Š., Vorčáková, K., Jampílek, J., Vančo, J., Šimůnek, P., Královec, K., Brůčková, L., Mandíková, J., & Trejtnar, F. (2013). Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors. Bioorganic & Medicinal Chemistry, 21(7), 1735-48. https://doi.org/10.1016/j.bmc.2013.01.052
Imramovský A, et al. Synthesis and in Vitro Evaluation of New Derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as Cholinesterase Inhibitors. Bioorg Med Chem. 2013 Apr 1;21(7):1735-48. PubMed PMID: 23462716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors. AU - Imramovský,Aleš, AU - Pejchal,Vladimír, AU - Štěpánková,Šárka, AU - Vorčáková,Katarína, AU - Jampílek,Josef, AU - Vančo,Ján, AU - Šimůnek,Petr, AU - Královec,Karel, AU - Brůčková,Lenka, AU - Mandíková,Jana, AU - Trejtnar,František, Y1 - 2013/02/01/ PY - 2012/12/03/received PY - 2013/01/22/revised PY - 2013/01/23/accepted PY - 2013/3/7/entrez PY - 2013/3/7/pubmed PY - 2013/8/30/medline SP - 1735 EP - 48 JF - Bioorganic & medicinal chemistry JO - Bioorg Med Chem VL - 21 IS - 7 N2 - A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, (1)H, (13)C and (19)F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/23462716/Synthesis_and_in_vitro_evaluation_of_new_derivatives_of_2_substituted_6_fluorobenzo[d]thiazoles_as_cholinesterase_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(13)00091-6 DB - PRIME DP - Unbound Medicine ER -