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Investigation on the effect of alkyl chain linked mono-thioureas as Jack bean urease inhibitors, SAR, pharmacokinetics ADMET parameters and molecular docking studies.
Bioorg Chem. 2019 05; 86:473-481.BC

Abstract

The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis. All the compounds displayed remarkable potency against urease inhibition as compared to thiourea standard. It was found that novel compounds fulfill the criteria of drug-likeness by obeying Lipinski's rule of five. Particularly compound 4a and 4c can serve as lead molecules in 4D (drug designing discovery and development). Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity of the molecules.

Authors+Show Affiliations

Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan. Electronic address: fayazali@chem.qau.edu.pk.Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan. Electronic address: mfaisal4646@gmail.com.Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan. Electronic address: aamersaeed@yahoo.com.Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan.Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.Cardiovascular and Metabolic Research Unit, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada.Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan.Institute of biochemistry, University of Sindh, Jamshoro 76080, Pakistan.Department of Physiology, University of Sindh, Jamshoro 76080, Pakistan.Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan.Department of Chemistry, Abdul Wali Khan University, Mardan, Khybder Pakhtunkhwa, Pakistan.Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam 314-701, Republic of Korea.Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudehak-Ro, Gongju, Chungnam 314-701, Republic of Korea.

Pub Type(s)

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

Language

eng

PubMed ID

30772648

Citation

Larik, Fayaz Ali, et al. "Investigation On the Effect of Alkyl Chain Linked Mono-thioureas as Jack Bean Urease Inhibitors, SAR, Pharmacokinetics ADMET Parameters and Molecular Docking Studies." Bioorganic Chemistry, vol. 86, 2019, pp. 473-481.
Larik FA, Faisal M, Saeed A, et al. Investigation on the effect of alkyl chain linked mono-thioureas as Jack bean urease inhibitors, SAR, pharmacokinetics ADMET parameters and molecular docking studies. Bioorg Chem. 2019;86:473-481.
Larik, F. A., Faisal, M., Saeed, A., Channar, P. A., Korabecny, J., Jabeen, F., Mahar, I. A., Kazi, M. A., Abbas, Q., Murtaza, G., Khan, G. S., Hassan, M., & Seo, S. Y. (2019). Investigation on the effect of alkyl chain linked mono-thioureas as Jack bean urease inhibitors, SAR, pharmacokinetics ADMET parameters and molecular docking studies. Bioorganic Chemistry, 86, 473-481. https://doi.org/10.1016/j.bioorg.2019.02.011
Larik FA, et al. Investigation On the Effect of Alkyl Chain Linked Mono-thioureas as Jack Bean Urease Inhibitors, SAR, Pharmacokinetics ADMET Parameters and Molecular Docking Studies. Bioorg Chem. 2019;86:473-481. PubMed PMID: 30772648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Investigation on the effect of alkyl chain linked mono-thioureas as Jack bean urease inhibitors, SAR, pharmacokinetics ADMET parameters and molecular docking studies. AU - Larik,Fayaz Ali, AU - Faisal,Muhammad, AU - Saeed,Aamer, AU - Channar,Pervaiz Ali, AU - Korabecny,Jan, AU - Jabeen,Farukh, AU - Mahar,Ihsan Ali, AU - Kazi,Mehar Ali, AU - Abbas,Qamar, AU - Murtaza,Ghulam, AU - Khan,Gul Shahzada, AU - Hassan,Mubashir, AU - Seo,Sung-Yum, Y1 - 2019/02/08/ PY - 2018/12/13/received PY - 2019/01/30/revised PY - 2019/02/03/accepted PY - 2019/2/18/pubmed PY - 2020/4/14/medline PY - 2019/2/18/entrez KW - Acyl thioureas KW - Antioxidant KW - Jack bean urease KW - Kinetic mechanism KW - Lipinski’s rules KW - Molecular modeling KW - Urease SP - 473 EP - 481 JF - Bioorganic chemistry JO - Bioorg Chem VL - 86 N2 - The increasing resistance of pathogens to common antibiotics, as well as the need to control urease activity to improve the yield of soil nitrogen fertilization in agricultural applications, has stimulated the development of novel classes of molecules that target urease as an enzyme. In this context, the newly developed compounds on the basis of 1-heptanoyl-3-arylthiourea family were evaluated for Jack bean urease enzyme inhibition activity to validate their role as potent inhibitors of this enzyme. 1-Heptanoyl-3-arylthioureas were obtained in excellent yield and characterized through spectral and elemental analysis. All the compounds displayed remarkable potency against urease inhibition as compared to thiourea standard. It was found that novel compounds fulfill the criteria of drug-likeness by obeying Lipinski's rule of five. Particularly compound 4a and 4c can serve as lead molecules in 4D (drug designing discovery and development). Kinetic mechanism and molecular docking studies also carried out to delineate the mode of inhibition and binding affinity of the molecules. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/30772648/Investigation_on_the_effect_of_alkyl_chain_linked_mono_thioureas_as_Jack_bean_urease_inhibitors_SAR_pharmacokinetics_ADMET_parameters_and_molecular_docking_studies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(18)31466-4 DB - PRIME DP - Unbound Medicine ER -