Tags

Type your tag names separated by a space and hit enter

Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives as monoamine oxidase inhibitors.
Arch Pharm (Weinheim). 2018 Jul; 351(7):e1800082.AP

Abstract

In an effort to develop potent monoamine oxidase (MAO) inhibitors, new pyrrole derivatives were obtained via the selective reduction of the CC bonds of 1-(1-methyl-1H-pyrrol-2-yl)-3-[5-(aryl)furan-2-yl]prop-2-en-1-ones through palladium catalyzed hydrogenation in ethanol. The synthesized compounds were screened for their inhibitory effects on MAO-A and MAO-B by an in vitro fluorometric method. The selectivity index (SI) value was given as the ratio of IC50 (MAO-A)/IC50 (MAO-B) for each compound. 3-(5-(4-Chlorophenyl)furan-2-yl)-1-(1-methyl-1H-pyrrol-2-yl)propan-1-one (6) was identified as the most selective MAO-A inhibitor in this series, with an IC50 value of 0.162 µM and a SI value of 0.002. Kinetic studies were also carried out to assess the nature of MAO-A inhibition by compound 6. According to Lineweaver-Burk plots, compound 6 was found to be a competitive MAO-A inhibitor and the Ki value of compound 6 was determined as 0.1221 μM. Docking studies were performed for compound 6 and clorgyline using the human MAO-A crystal structure (PDB ID: 2Z5Y). The docking results showed that compound 6 presented similar interactions as clorgyline in the active center cavity of the enzyme. Molinspiration software was used to determine the physicochemical parameters of all compounds for an evaluation of their compliance to Lipinski's rule of five. Compound 6 did not violate Lipinski's rule, making it a potential orally bioavailable therapeutic agent.

Authors+Show Affiliations

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29963739

Citation

Altintop, Mehlika D., et al. "Design, Synthesis, in Vitro and in Silico Evaluation of New Pyrrole Derivatives as Monoamine Oxidase Inhibitors." Archiv Der Pharmazie, vol. 351, no. 7, 2018, pp. e1800082.
Altintop MD, Sever B, Osmaniye D, et al. Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives as monoamine oxidase inhibitors. Arch Pharm (Weinheim). 2018;351(7):e1800082.
Altintop, M. D., Sever, B., Osmaniye, D., Sağlık, B. N., & Özdemir, A. (2018). Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives as monoamine oxidase inhibitors. Archiv Der Pharmazie, 351(7), e1800082. https://doi.org/10.1002/ardp.201800082
Altintop MD, et al. Design, Synthesis, in Vitro and in Silico Evaluation of New Pyrrole Derivatives as Monoamine Oxidase Inhibitors. Arch Pharm (Weinheim). 2018;351(7):e1800082. PubMed PMID: 29963739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis, in vitro and in silico evaluation of new pyrrole derivatives as monoamine oxidase inhibitors. AU - Altintop,Mehlika D, AU - Sever,Belgin, AU - Osmaniye,Derya, AU - Sağlık,Begüm N, AU - Özdemir,Ahmet, Y1 - 2018/05/22/ PY - 2018/03/19/received PY - 2018/04/25/revised PY - 2018/05/02/accepted PY - 2018/7/3/entrez PY - 2018/7/3/pubmed PY - 2018/10/20/medline KW - Lipinski's rule of five KW - docking KW - furan KW - monoamine oxidase KW - pyrrole SP - e1800082 EP - e1800082 JF - Archiv der Pharmazie JO - Arch. Pharm. (Weinheim) VL - 351 IS - 7 N2 - In an effort to develop potent monoamine oxidase (MAO) inhibitors, new pyrrole derivatives were obtained via the selective reduction of the CC bonds of 1-(1-methyl-1H-pyrrol-2-yl)-3-[5-(aryl)furan-2-yl]prop-2-en-1-ones through palladium catalyzed hydrogenation in ethanol. The synthesized compounds were screened for their inhibitory effects on MAO-A and MAO-B by an in vitro fluorometric method. The selectivity index (SI) value was given as the ratio of IC50 (MAO-A)/IC50 (MAO-B) for each compound. 3-(5-(4-Chlorophenyl)furan-2-yl)-1-(1-methyl-1H-pyrrol-2-yl)propan-1-one (6) was identified as the most selective MAO-A inhibitor in this series, with an IC50 value of 0.162 µM and a SI value of 0.002. Kinetic studies were also carried out to assess the nature of MAO-A inhibition by compound 6. According to Lineweaver-Burk plots, compound 6 was found to be a competitive MAO-A inhibitor and the Ki value of compound 6 was determined as 0.1221 μM. Docking studies were performed for compound 6 and clorgyline using the human MAO-A crystal structure (PDB ID: 2Z5Y). The docking results showed that compound 6 presented similar interactions as clorgyline in the active center cavity of the enzyme. Molinspiration software was used to determine the physicochemical parameters of all compounds for an evaluation of their compliance to Lipinski's rule of five. Compound 6 did not violate Lipinski's rule, making it a potential orally bioavailable therapeutic agent. SN - 1521-4184 UR - https://www.unboundmedicine.com/medline/citation/29963739/Design_synthesis_in_vitro_and_in_silico_evaluation_of_new_pyrrole_derivatives_as_monoamine_oxidase_inhibitors_ L2 - https://doi.org/10.1002/ardp.201800082 DB - PRIME DP - Unbound Medicine ER -