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Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones.
Chem Biodivers. 2019 Dec; 16(12):e1900503.CB

Abstract

A series of 2,5-bis(alkyl/arylamino)-1,4-benzoquinones (1-12) were investigated in vitro for their potential to inhibit the activity of jack bean urease. Compounds 1-6, 8, 9, 11 and 12 effectively inhibited the jack bean urease activity by 90.8 % when tested at 5 μm, whereas 7 and 10 had relatively little effect. The IC50 for most compounds was in the nanomolar range (31.4 nm and 36.0 nm for 2 and 8, respectively). The mechanism of enzyme inhibition shown by 2 and 8 is typical of mixed-type inhibitors, whose affinity for the active site is over 6- and 2-fold higher (Ki =30.0 and 22.8 nm, for 2 and 8, respectively) than that of an allosteric site. Molecular docking studies revealed that both 2 and 8 establish hydrogen bonds with the amino acids residues Asp494, Met588, His593 and Ala636 in the active site of jack bean urease. These results indicate that such aminoquinones are useful leads for the development of more efficient urease inhibitors of wider utility.

Authors+Show Affiliations

Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil.Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil. Department of Chemistry, Universidade Federal de Viçosa, Av. P. H. Rofls, s/n, 36570-000, Viçosa, MG, Brazil.Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil.Departamento de Botânica, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil.Departamento de Botânica, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil.Department of Chemistry, Campus Universitário, Universidade Federal de Lavras, 37200-000, Lavras, MG, Brazil.Departamento de Botânica, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, 31270-901, Belo Horizonte, MG, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31660678

Citation

Nain-Perez, Amalyn, et al. "Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones." Chemistry & Biodiversity, vol. 16, no. 12, 2019, pp. e1900503.
Nain-Perez A, Barbosa LCA, Rodríguez-Hernández D, et al. Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones. Chem Biodivers. 2019;16(12):e1900503.
Nain-Perez, A., Barbosa, L. C. A., Rodríguez-Hernández, D., Mota, Y. C. C., Silva, T. F., Ramalho, T. C., & Modolo, L. V. (2019). Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones. Chemistry & Biodiversity, 16(12), e1900503. https://doi.org/10.1002/cbdv.201900503
Nain-Perez A, et al. Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones. Chem Biodivers. 2019;16(12):e1900503. PubMed PMID: 31660678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones. AU - Nain-Perez,Amalyn, AU - Barbosa,Luiz C A, AU - Rodríguez-Hernández,Diego, AU - Mota,Yane C C, AU - Silva,Thamara F, AU - Ramalho,Teodorico C, AU - Modolo,Luzia V, Y1 - 2019/12/05/ PY - 2019/09/13/received PY - 2019/10/25/accepted PY - 2019/10/30/pubmed PY - 2020/1/7/medline PY - 2019/10/30/entrez KW - 2,5-diamino-1,4-benzoquinones KW - jack bean urease KW - molecular docking KW - urease inhibitors SP - e1900503 EP - e1900503 JF - Chemistry & biodiversity JO - Chem Biodivers VL - 16 IS - 12 N2 - A series of 2,5-bis(alkyl/arylamino)-1,4-benzoquinones (1-12) were investigated in vitro for their potential to inhibit the activity of jack bean urease. Compounds 1-6, 8, 9, 11 and 12 effectively inhibited the jack bean urease activity by 90.8 % when tested at 5 μm, whereas 7 and 10 had relatively little effect. The IC50 for most compounds was in the nanomolar range (31.4 nm and 36.0 nm for 2 and 8, respectively). The mechanism of enzyme inhibition shown by 2 and 8 is typical of mixed-type inhibitors, whose affinity for the active site is over 6- and 2-fold higher (Ki =30.0 and 22.8 nm, for 2 and 8, respectively) than that of an allosteric site. Molecular docking studies revealed that both 2 and 8 establish hydrogen bonds with the amino acids residues Asp494, Met588, His593 and Ala636 in the active site of jack bean urease. These results indicate that such aminoquinones are useful leads for the development of more efficient urease inhibitors of wider utility. SN - 1612-1880 UR - https://www.unboundmedicine.com/medline/citation/31660678/Antiureolytic_Activity_of_Substituted_25_Diaminobenzoquinones_ L2 - https://doi.org/10.1002/cbdv.201900503 DB - PRIME DP - Unbound Medicine ER -