Tags

Type your tag names separated by a space and hit enter

Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking.
Chem Biodivers. 2017 Aug; 14(8)CB

Abstract

The current research article reports the synthesis of coumarinyl pyrazolinyl thioamide derivatives and their biological activity as inhibitors of jack bean urease. The coumarinyl pyrazolinyl thioamides were synthesized by reacting thiosemicarbazide with newly synthesized chalcones to afford the products in good yields and the synthesized compounds were purified by recrystallization. Coumarinyl pyrazolinyl thioamide derivatives 5a - 5q showed significant activity against Urease enzyme and also exhibited good antioxidant potential. The compound 3-(2-oxo-2H-chromen-3-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (5n) was found to be superior agent in the series with an IC50 = 0.358 ± 0.017 μm compared to standard thiourea with an IC50 = 4720 ± 174 μm. To undermine the binding mode of inhibition kinetic studies were performed for most potent derivative and it was found that compound 5n inhibits urease enzyme by non-competitive mode of inhibition. Molecular docking studies were carried out to delineate the binding affinity of the synthesized derivatives.

Authors+Show Affiliations

Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.Department of Chemistry, Quaid-I-Azam University, Islamabad, 45320, Pakistan.Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam, 314-701, Korea.Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam, 314-701, Korea.Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam, 314-701, Korea.Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam, 314-701, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28574649

Citation

Saeed, Aamer, et al. "Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking." Chemistry & Biodiversity, vol. 14, no. 8, 2017.
Saeed A, Mahesar PA, Channar PA, et al. Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking. Chem Biodivers. 2017;14(8).
Saeed, A., Mahesar, P. A., Channar, P. A., Larik, F. A., Abbas, Q., Hassan, M., Raza, H., & Seo, S. Y. (2017). Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking. Chemistry & Biodiversity, 14(8). https://doi.org/10.1002/cbdv.201700035
Saeed A, et al. Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking. Chem Biodivers. 2017;14(8) PubMed PMID: 28574649.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hybrid Pharmacophoric Approach in the Design and Synthesis of Coumarin Linked Pyrazolinyl as Urease Inhibitors, Kinetic Mechanism and Molecular Docking. AU - Saeed,Aamer, AU - Mahesar,Parvez Ali, AU - Channar,Pervaiz Ali, AU - Larik,Fayaz Ali, AU - Abbas,Qamar, AU - Hassan,Mubashir, AU - Raza,Hussain, AU - Seo,Sung-Yum, Y1 - 2017/08/07/ PY - 2017/01/27/received PY - 2017/05/31/accepted PY - 2017/6/3/pubmed PY - 2017/9/28/medline PY - 2017/6/3/entrez KW - Antioxidant activities KW - Coumarinyl pyrazolinyl thioamides KW - Hybrid pharmacophore KW - Jack bean urease inhibitors KW - Kinetics KW - Molecular docking KW - Synthesis JF - Chemistry & biodiversity JO - Chem Biodivers VL - 14 IS - 8 N2 - The current research article reports the synthesis of coumarinyl pyrazolinyl thioamide derivatives and their biological activity as inhibitors of jack bean urease. The coumarinyl pyrazolinyl thioamides were synthesized by reacting thiosemicarbazide with newly synthesized chalcones to afford the products in good yields and the synthesized compounds were purified by recrystallization. Coumarinyl pyrazolinyl thioamide derivatives 5a - 5q showed significant activity against Urease enzyme and also exhibited good antioxidant potential. The compound 3-(2-oxo-2H-chromen-3-yl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (5n) was found to be superior agent in the series with an IC50 = 0.358 ± 0.017 μm compared to standard thiourea with an IC50 = 4720 ± 174 μm. To undermine the binding mode of inhibition kinetic studies were performed for most potent derivative and it was found that compound 5n inhibits urease enzyme by non-competitive mode of inhibition. Molecular docking studies were carried out to delineate the binding affinity of the synthesized derivatives. SN - 1612-1880 UR - https://www.unboundmedicine.com/medline/citation/28574649/Hybrid_Pharmacophoric_Approach_in_the_Design_and_Synthesis_of_Coumarin_Linked_Pyrazolinyl_as_Urease_Inhibitors_Kinetic_Mechanism_and_Molecular_Docking_ L2 - https://doi.org/10.1002/cbdv.201700035 DB - PRIME DP - Unbound Medicine ER -