Identification of a Prenyl Chalcone as a Competitive Lipoxygenase Inhibitor: Screening, Biochemical Evaluation and Molecular Modeling Studies

Author(s):Show less -

Zeraik, Maria Luiza ^{[1, 2]} ; Pauli, Ivani ^[3] ; Dutra, Luiz A. ^[2] ; Cruz, Raquel S. ^[2] ; Valli, Marilia ^{[2, 3]} ; Paracatu, Luana C. ^[4] ; de Faria, Carolina M. Q. G. ^[4] ; Ximenes, Valdecir F. ^[4] ; Regasini, Luis O. ^{[2, 5]} ; Andricopulo, Adriano D. ^[3] ; Bolzani, Vanderlan S. ^[2]

Affiliation

^[1] Univ Estadual Londrina UEL, Dept Quim, Lab Fitoquim & Biomol LabFitoBio, BR-86051990 Londrina, PR - Brazil

^[2] Univ Estadual Paulista UNESP, Inst Quim, Dept Quim Organ, Nucleo Bioensaios Biossintese & Ecofisiol Prod Na, BR-14800060 Araraquara, SP - Brazil

^[3] Univ Sao Paulo, Ctr Pesquisa & Inovacao Biodiversidade & Farmacos, Lab Quim Med & Computac LQMC, Inst Fis Sao Carlos, BR-13563120 Sao Carlos, SP - Brazil

^[4] Univ Estadual Paulista UNESP, Dept Quim, Fac Ciencias, BR-17020360 Bauru, SP - Brazil

^[5] Univ Estadual Paulista UNESP, Inst Biociencias Letras & Ciencias Exatas, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: Molecules; v. 26, n. 8 APR 2021.
• Web of Science Citations: 1

Abstract

Cyclooxygenase (COX) and lipoxygenase (LOX) are key targets for the development of new anti-inflammatory agents. LOX, which is involved in the biosynthesis of mediators in inflammation and allergic reactions, was selected for a biochemical screening campaign to identify LOX inhibitors by employing the main natural product library of Brazilian biodiversity. Two prenyl chalcones were identified as potent inhibitors of LOX-1 in the screening. The most active compound, (E)-2-O-farnesyl chalcone, decreased the rate of oxygen consumption to an extent similar to that of the positive control, nordihydroguaiaretic acid. Additionally, studies on the mechanism of the action indicated that (E)-2-O-farnesyl chalcone is a competitive LOX-1 inhibitor. Molecular modeling studies indicated the importance of the prenyl moieties for the binding of the inhibitors to the LOX binding site, which is related to their pharmacological properties. (AU)

• FAPESP's process: 10/01506-7 - Synthesis of prenylated chalcones as potential alpha-glucosidase inhibitors
• Grantee: Luiz Antonio Dutra
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 11/03017-6 - Natural products from plants of Cerrado and Atlantic Forest, potential models and useful for identifying prototypes with oxidizing action on neutrophils and myeloperoxidase (MPO) enzyme
• Grantee: Maria Luiza Zeraik
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/05967-3 - Understanding the biological function of Natural Products' scaffolds from Databases for the design of active compounds for the treatment of infectious diseases
• Grantee: Marilia Valli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/18445-5 - Synthesis, studies and applications of fluorescent and circular dichroic probes for characterization of interactions with proteins, DNA and determination of enzymatic activity
• Grantee: Valdecir Farias Ximenes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/15457-0 - Synthesis of aminochalcones as potential alpha-glucosidase inhibitors
• Grantee: Raquel Sabará da Cruz
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants