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IDENTIFICATION OF A SELECTIVE PDE4B INHIBITOR FROM BRYOPHYLLUM PINNATUM BY TARGET FISHING STUDY AND IN VITRO EVALUATION OF QUERCETIN 3-O-α-L-ARABINOPYRANOSYL-(1→2)-O-α-L-RHAMNOPYRANOSIDE
Produtos naturais
Flavonóides
Dinâmica molecular
Triagem virtual inversa
Natural products
PDE4B
Flavonoid
Inverse virtual screening
Molecular dynamics
Author
Affilliation
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Química Farmacêutica. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Produtos Naturais Bioativos. Natal, RN, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Université Paris Descartes. Laboratoire de Pharmacognosis. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Química Farmacêutica Computacional. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Produtos Naturais Bioativos. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Química Farmacêutica Computacional. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Produtos Naturais Bioativos. Natal, RN, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Université Paris Descartes. Laboratoire de Pharmacognosis. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Química Farmacêutica Computacional. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Produtos Naturais Bioativos. Natal, RN, Brasil.
Universidade Federal do Rio Grande do Norte. Departamento de Farmácia. Laboratório de Química Farmacêutica Computacional. Natal, RN, Brasil.
Abstract
Natural products are considered an important source of bioactive compounds especially in biodiversity-rich countries like Brazil. The identification of potential targets is crucial to the development of drugs from natural sources. In this context, in silico methodologies, such as inverse virtual screening (target fishing), are interesting tools as they are a rational and direct method that reduces costs and experimental time. Among the species of Brazilian biomes, Bryophyllum pinnatum (Lam.) Oken, native to Madagascar, is widely used by the population to treat inflammation conditions. It has a remarkable presence of flavonoids, including quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (1), considered one of its major compounds. However, until now there were no studies addressing its putative mechanism of action and explaining its pharmacological action. The enzyme PDE4B, known as an antiinflammatory protein, was indicated as a promising target by target fishing methods. This activity was confirmed by in vitro enzymatic inhibition, and an expressive selectivity of PDE4B over PDE4A was demonstrated. The interactions were investigated through molecular dynamics simulations. The results were pioneering, representing an advance in the investigation of the antiinflammatory action of B. pinnatum and confirm the potential of the flavonoid as a chemical extract marker. Also, the flavonoid was shown to be a promising lead for the design of other selective PDE4B blockers to treat inflammatory diseases.
Keywords in Portuguese
Briophyllum pinnatumProdutos naturais
Flavonóides
Dinâmica molecular
Triagem virtual inversa
Keywords
Bryophyllum pinnatumNatural products
PDE4B
Flavonoid
Inverse virtual screening
Molecular dynamics
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