Tags

Type your tag names separated by a space and hit enter

Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation.
Bioorg Chem. 2019 06; 87:1-11.BC

Abstract

An efficient, one-pot and four-component synthesis of a new series of 2,3-disubstituted isoindolin-1-ones is described and their Jack bean urease inhibitory activities are evaluated. Heating a mixture of 1,1-bis(methylthio)-2-nitroethene, a 1,2-diamine, a 2-formylbenzoic acid and a primary amine in EtOH for 3.5 h afforded the corresponding 2,3-disubstituted isoindolin-1-ones in good to excellent yields. All sixteen synthesized isoindolin-1-one derivatives 5a-p showed urease inhibitory activity. Among them, 5c showed the most urease inhibitory activity (IC50 = 10.07 ± 0.28 µM) being over 2-fold more potent than thiourea (IC50 = 22.01 ± 0.10 µM) and 10-fold than hydroxyurea (IC50 = 100.00 ± 0.02 µM) as the standard inhibitors, respectively. Also, results from molecular docking studies were in good agreement with those obtained from in vitro tests.

Authors+Show Affiliations

School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran. Electronic address: madib@khayam.ut.ac.ir.Computational Chemistry Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran.Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.Computational Chemistry Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: amanlou@tums.ac.ir.

Pub Type(s)

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

Language

eng

PubMed ID

30852231

Citation

Peytam, Fariba, et al. "Isoindolin-1-one Derivatives as Urease Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and In-silico ADME Evaluation." Bioorganic Chemistry, vol. 87, 2019, pp. 1-11.
Peytam F, Adib M, Mahernia S, et al. Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation. Bioorg Chem. 2019;87:1-11.
Peytam, F., Adib, M., Mahernia, S., Rahmanian-Jazi, M., Jahani, M., Masoudi, B., Mahdavi, M., & Amanlou, M. (2019). Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation. Bioorganic Chemistry, 87, 1-11. https://doi.org/10.1016/j.bioorg.2019.02.051
Peytam F, et al. Isoindolin-1-one Derivatives as Urease Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and In-silico ADME Evaluation. Bioorg Chem. 2019;87:1-11. PubMed PMID: 30852231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isoindolin-1-one derivatives as urease inhibitors: Design, synthesis, biological evaluation, molecular docking and in-silico ADME evaluation. AU - Peytam,Fariba, AU - Adib,Mehdi, AU - Mahernia,Shabnam, AU - Rahmanian-Jazi,Mahmoud, AU - Jahani,Mehdi, AU - Masoudi,Behrad, AU - Mahdavi,Mohammad, AU - Amanlou,Massoud, Y1 - 2019/02/25/ PY - 2018/11/16/received PY - 2019/02/22/revised PY - 2019/02/23/accepted PY - 2019/3/11/pubmed PY - 2020/8/21/medline PY - 2019/3/11/entrez KW - 2,3-Disubstituted isoindolin-1-ones KW - In-silico ADME evaluation KW - Molecular docking KW - Urease inhibition SP - 1 EP - 11 JF - Bioorganic chemistry JO - Bioorg Chem VL - 87 N2 - An efficient, one-pot and four-component synthesis of a new series of 2,3-disubstituted isoindolin-1-ones is described and their Jack bean urease inhibitory activities are evaluated. Heating a mixture of 1,1-bis(methylthio)-2-nitroethene, a 1,2-diamine, a 2-formylbenzoic acid and a primary amine in EtOH for 3.5 h afforded the corresponding 2,3-disubstituted isoindolin-1-ones in good to excellent yields. All sixteen synthesized isoindolin-1-one derivatives 5a-p showed urease inhibitory activity. Among them, 5c showed the most urease inhibitory activity (IC50 = 10.07 ± 0.28 µM) being over 2-fold more potent than thiourea (IC50 = 22.01 ± 0.10 µM) and 10-fold than hydroxyurea (IC50 = 100.00 ± 0.02 µM) as the standard inhibitors, respectively. Also, results from molecular docking studies were in good agreement with those obtained from in vitro tests. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/30852231/Isoindolin_1_one_derivatives_as_urease_inhibitors:_Design_synthesis_biological_evaluation_molecular_docking_and_in_silico_ADME_evaluation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(18)31332-4 DB - PRIME DP - Unbound Medicine ER -