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Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors.
Biomed Res Int. 2020; 2020:8867407.BR

Abstract

A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines 1a-b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a-f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC501.6 ± 0.2 nM, better than the standard thiourea having IC50472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound 4b and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver-Burk plots (kinetics study) indicated about 4b derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds 4b and 4e have binding energies of -7.8 and -7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative 4b is a highly potent urease inhibitor, better than the standard thiourea.

Authors+Show Affiliations

Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan.Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan.Department of Zoology, University of Gujrat, Gujrat 50700, Pakistan.Department of Zoology, University of Gujrat, Gujrat 50700, Pakistan.Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan.Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan.Department of Physiology, University of Sindh, Jamshoro, Pakistan.Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.Department of Pharmacy, SBK Women University, Quetta, Balochistan, Pakistan.Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Pakistan. Institute of Fundamental Medicine, Department of Genetics, Kazan Federal University, Russia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33426080

Citation

Rashid, Muhammad, et al. "Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors." BioMed Research International, vol. 2020, 2020, p. 8867407.
Rashid M, Rafique H, Roshan S, et al. Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors. Biomed Res Int. 2020;2020:8867407.
Rashid, M., Rafique, H., Roshan, S., Shamas, S., Iqbal, Z., Ashraf, Z., Abbas, Q., Hassan, M., Qureshi, Z. U. R., & Asad, M. H. H. B. (2020). Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors. BioMed Research International, 2020, 8867407. https://doi.org/10.1155/2020/8867407
Rashid M, et al. Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors. Biomed Res Int. 2020;2020:8867407. PubMed PMID: 33426080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzyme Inhibitory Kinetics and Molecular Docking Studies of Halo-Substituted Mixed Ester/Amide-Based Derivatives as Jack Bean Urease Inhibitors. AU - Rashid,Muhammad, AU - Rafique,Hummera, AU - Roshan,Sadia, AU - Shamas,Shazia, AU - Iqbal,Zafar, AU - Ashraf,Zaman, AU - Abbas,Qamar, AU - Hassan,Mubashir, AU - Qureshi,Zia Ur Rahman, AU - Asad,Muhammad Hassham Hassan Bin, Y1 - 2020/12/24/ PY - 2020/09/02/received PY - 2020/11/28/revised PY - 2020/12/15/accepted PY - 2021/1/11/entrez PY - 2021/1/12/pubmed PY - 2021/5/25/medline SP - 8867407 EP - 8867407 JF - BioMed research international JO - Biomed Res Int VL - 2020 N2 - A series of halo-substituted mixed ester/amide-based analogues 4a-l have been prepared as jack bean urease inhibitor, which showed good to excellent inhibition of enzyme activity. The role of halo-substituted benzoyl moieties and alkyl substituted anilines in urease inhibitory kinetics was also investigated. The alkyl-substituted anilines 1a-b reacted with chloroacetyl chloride to afford intermediates 2a-b, which were then reacted with different halo-substituted benzoic acids 3a-f to prepare the title compounds 4a-l. The chemical structures of final products 4a-l were ascertained by FTIR, 1H NMR, 13C NMR, and mass spectra. The compound 4b showed remarkable activity with IC501.6 ± 0.2 nM, better than the standard thiourea having IC50472.1 ± 135.1 nM. The 2-chloro-substituted phenyl ring on one side of compound 4b and 4-isopropyl-substituted benzene on the other side play an essential role in inhibition of urease activity. Lineweaver-Burk plots (kinetics study) indicated about 4b derivative as a mixed type of inhibitor. The virtual screening performed against urease enzyme (PDBID 4H9M) showed that compounds 4b and 4e have binding energies of -7.8 and -7.9 Kcal/mol, respectively. Based upon our results, it was found that derivative 4b is a highly potent urease inhibitor, better than the standard thiourea. SN - 2314-6141 UR - https://www.unboundmedicine.com/medline/citation/33426080/Enzyme_Inhibitory_Kinetics_and_Molecular_Docking_Studies_of_Halo_Substituted_Mixed_Ester/Amide_Based_Derivatives_as_Jack_Bean_Urease_Inhibitors_ L2 - https://doi.org/10.1155/2020/8867407 DB - PRIME DP - Unbound Medicine ER -