Tags

Type your tag names separated by a space and hit enter

Design, synthesis, kinetic mechanism and molecular docking studies of novel 1-pentanoyl-3-arylthioureas as inhibitors of mushroom tyrosinase and free radical scavengers.
Eur J Med Chem. 2017 Dec 01; 141:273-281.EJ

Abstract

A series of novel 1-pentanoyl-3-arylthioureas was designed as new mushroom tyrosinase inhibitors and free radical scavengers. The title compounds were obtained in excellent yield and characterized by FTIR, 1H NMR, 13C NMR and X-ray crystallography in case of compound (4a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 1-Pentanoyl-3-(4-methoxyphenyl) thiourea (4f) showed tyrosinase inhibitory activity (IC50 1.568 ± 0.01 mM) comparable to Kojic acid (IC50 16.051 ± 1.27 mM). Interestingly compound 4f exhibited higher antioxidant potential compared to other derivatives. The docking studies of synthesized 1-Pentanoyl-3-arylthioureas analogues were also carried out against tyrosinase protein (PDBID 2ZMX) to compare the binding affinities with IC50 values. The predicted binding affinities are in good agreement with the IC50 values as compound (4f) showed highest binding affinity (-7.50 kcal/mol) compared to others derivatives. The kinetic mechanism analyzed by Line-weavere Burk plots exhibited that compound (4f) inhibit the enzyme inhibits the tyrosinase non-competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (4f) is 1.10 μM. It was also found from kinetic analysis that derivative 4f irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound (4f) may serve as lead structure for the design of more potent tyrosinase inhibitors.

Authors+Show Affiliations

Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan.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.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, Republic of Korea.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.Institut für Anorganische Chemie, J.W.-Goethe-Universität, Max-von-Laue-Str.7, D-60438 Frankfurt/Main, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29040952

Citation

Larik, Fayaz Ali, et al. "Design, Synthesis, Kinetic Mechanism and Molecular Docking Studies of Novel 1-pentanoyl-3-arylthioureas as Inhibitors of Mushroom Tyrosinase and Free Radical Scavengers." European Journal of Medicinal Chemistry, vol. 141, 2017, pp. 273-281.
Larik FA, Saeed A, Channar PA, et al. Design, synthesis, kinetic mechanism and molecular docking studies of novel 1-pentanoyl-3-arylthioureas as inhibitors of mushroom tyrosinase and free radical scavengers. Eur J Med Chem. 2017;141:273-281.
Larik, F. A., Saeed, A., Channar, P. A., Muqadar, U., Abbas, Q., Hassan, M., Seo, S. Y., & Bolte, M. (2017). Design, synthesis, kinetic mechanism and molecular docking studies of novel 1-pentanoyl-3-arylthioureas as inhibitors of mushroom tyrosinase and free radical scavengers. European Journal of Medicinal Chemistry, 141, 273-281. https://doi.org/10.1016/j.ejmech.2017.09.059
Larik FA, et al. Design, Synthesis, Kinetic Mechanism and Molecular Docking Studies of Novel 1-pentanoyl-3-arylthioureas as Inhibitors of Mushroom Tyrosinase and Free Radical Scavengers. Eur J Med Chem. 2017 Dec 1;141:273-281. PubMed PMID: 29040952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis, kinetic mechanism and molecular docking studies of novel 1-pentanoyl-3-arylthioureas as inhibitors of mushroom tyrosinase and free radical scavengers. AU - Larik,Fayaz Ali, AU - Saeed,Aamer, AU - Channar,Pervaiz Ali, AU - Muqadar,Urooj, AU - Abbas,Qamar, AU - Hassan,Mubashir, AU - Seo,Sung-Yum, AU - Bolte,Michael, Y1 - 2017/09/29/ PY - 2016/11/01/received PY - 2017/09/25/revised PY - 2017/09/27/accepted PY - 2017/10/19/pubmed PY - 2017/12/8/medline PY - 2017/10/18/entrez KW - Crystal structure KW - Kinetic mechanism KW - Molecular docking KW - Mushroom tyrosinase inhibitor KW - Synthesis KW - Thiourea derivatives SP - 273 EP - 281 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 141 N2 - A series of novel 1-pentanoyl-3-arylthioureas was designed as new mushroom tyrosinase inhibitors and free radical scavengers. The title compounds were obtained in excellent yield and characterized by FTIR, 1H NMR, 13C NMR and X-ray crystallography in case of compound (4a). The inhibitory effects on mushroom tyrosinase and DPPH were evaluated and it was observed that 1-Pentanoyl-3-(4-methoxyphenyl) thiourea (4f) showed tyrosinase inhibitory activity (IC50 1.568 ± 0.01 mM) comparable to Kojic acid (IC50 16.051 ± 1.27 mM). Interestingly compound 4f exhibited higher antioxidant potential compared to other derivatives. The docking studies of synthesized 1-Pentanoyl-3-arylthioureas analogues were also carried out against tyrosinase protein (PDBID 2ZMX) to compare the binding affinities with IC50 values. The predicted binding affinities are in good agreement with the IC50 values as compound (4f) showed highest binding affinity (-7.50 kcal/mol) compared to others derivatives. The kinetic mechanism analyzed by Line-weavere Burk plots exhibited that compound (4f) inhibit the enzyme inhibits the tyrosinase non-competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (4f) is 1.10 μM. It was also found from kinetic analysis that derivative 4f irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound (4f) may serve as lead structure for the design of more potent tyrosinase inhibitors. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/29040952/Design_synthesis_kinetic_mechanism_and_molecular_docking_studies_of_novel_1_pentanoyl_3_arylthioureas_as_inhibitors_of_mushroom_tyrosinase_and_free_radical_scavengers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(17)30774-2 DB - PRIME DP - Unbound Medicine ER -