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Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1-(2-(4-isobutylphenyl) propanoyl)-3-arylthioureas as Jack bean urease inhibitors.
Chem Biol Drug Des. 2018 02; 91(2):434-447.CB

Abstract

In this article, synthesis of a novel 1-(2-(4-isobutylphenyl)propanoyl)-3-arylthioureas (4a-j) as jack bean urease inhibitors has been described. Freshly prepared 2-(4-isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds 4e, 4h, and 4j showed IC50 values 0.0086 nm, 0.0081 nm, and 0.0094 nm, respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing Ki value 0.0012 nm. The Ki values for 4e and 4j are 0.0025 nm and 0.003 nm, respectively. The antioxidant activity results reflected that compounds 4b, 4i, and 4j showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds were also performed, and results showed that the wet laboratory findings are in good agreement to the dry laboratory results. Based upon our results, it is proposed that compound 4h may act as a lead candidate to design the clinically useful urease inhibitors.

Authors+Show Affiliations

Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.Department of Chemistry, Allama Iqbal Open University, Islamabad, Pakistan.Department of Biology, College of Natural Sciences, Kongju National University, Gongju, Korea.Department of Biology, College of Natural Sciences, Kongju National University, Gongju, Korea.Department of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28834266

Citation

Abdul Fattah, Tanzeela, et al. "Synthesis, Enzyme Inhibitory Kinetics, and Computational Studies of Novel 1-(2-(4-isobutylphenyl) Propanoyl)-3-arylthioureas as Jack Bean Urease Inhibitors." Chemical Biology & Drug Design, vol. 91, no. 2, 2018, pp. 434-447.
Abdul Fattah T, Saeed A, Channar PA, et al. Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1-(2-(4-isobutylphenyl) propanoyl)-3-arylthioureas as Jack bean urease inhibitors. Chem Biol Drug Des. 2018;91(2):434-447.
Abdul Fattah, T., Saeed, A., Channar, P. A., Ashraf, Z., Abbas, Q., Hassan, M., & Larik, F. A. (2018). Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1-(2-(4-isobutylphenyl) propanoyl)-3-arylthioureas as Jack bean urease inhibitors. Chemical Biology & Drug Design, 91(2), 434-447. https://doi.org/10.1111/cbdd.13090
Abdul Fattah T, et al. Synthesis, Enzyme Inhibitory Kinetics, and Computational Studies of Novel 1-(2-(4-isobutylphenyl) Propanoyl)-3-arylthioureas as Jack Bean Urease Inhibitors. Chem Biol Drug Des. 2018;91(2):434-447. PubMed PMID: 28834266.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, enzyme inhibitory kinetics, and computational studies of novel 1-(2-(4-isobutylphenyl) propanoyl)-3-arylthioureas as Jack bean urease inhibitors. AU - Abdul Fattah,Tanzeela, AU - Saeed,Aamer, AU - Channar,Pervaiz Ali, AU - Ashraf,Zaman, AU - Abbas,Qamar, AU - Hassan,Mubashir, AU - Larik,Fayaz Ali, Y1 - 2017/11/07/ PY - 2017/05/22/received PY - 2017/08/01/revised PY - 2017/08/11/accepted PY - 2017/8/24/pubmed PY - 2019/1/27/medline PY - 2017/8/24/entrez KW - Jack bean urease KW - computational studies KW - enzyme kinetics KW - synthesis KW - thioureas SP - 434 EP - 447 JF - Chemical biology & drug design JO - Chem Biol Drug Des VL - 91 IS - 2 N2 - In this article, synthesis of a novel 1-(2-(4-isobutylphenyl)propanoyl)-3-arylthioureas (4a-j) as jack bean urease inhibitors has been described. Freshly prepared 2-(4-isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds 4e, 4h, and 4j showed IC50 values 0.0086 nm, 0.0081 nm, and 0.0094 nm, respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing Ki value 0.0012 nm. The Ki values for 4e and 4j are 0.0025 nm and 0.003 nm, respectively. The antioxidant activity results reflected that compounds 4b, 4i, and 4j showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds were also performed, and results showed that the wet laboratory findings are in good agreement to the dry laboratory results. Based upon our results, it is proposed that compound 4h may act as a lead candidate to design the clinically useful urease inhibitors. SN - 1747-0285 UR - https://www.unboundmedicine.com/medline/citation/28834266/Synthesis_enzyme_inhibitory_kinetics_and_computational_studies_of_novel_1__2__4_isobutylphenyl__propanoyl__3_arylthioureas_as_Jack_bean_urease_inhibitors_ L2 - https://doi.org/10.1111/cbdd.13090 DB - PRIME DP - Unbound Medicine ER -