Pesquisa

Structural and mechanistic insight 24jul19

qua, 24 jul 2019

Publicado por

Authors:

Godoy,  Andre Schutzerde 1 ; Sachetto Fernandes,  Rafaela 1 ;  Campos Aguiar, Anna Caroline 1 ; Vieira Bueno, Renata 1 ; Roso Mesquita, Nathalya Cristina de Moraes 1 ;  Guido, Rafael Victorio Carvalho 1 ; Oliva, Glaucius 1


Abstract:

With almost half of the world population living at risk, tropical infectious diseases cause millions of deaths every year in developing countries. Considering the lack of economic prospects for investment in this field, approaches aiming the rational design of compounds, such as structure-based drug discovery (SBDD), fragment screening, target-based drug discovery, and drug repurposing are of special interest. Herein, we focused in the advances on the field of SBDD targeting arboviruses such as dengue, yellow fever, zika and chikungunya enzymes of the RNA replication complex (RC) and enzymes involved in a variety of pathways essential to ensure parasitic survival in the host, for malaria, Chagas e leishmaniasis diseases. We also highlighted successful examples such as promising new inhibitors and molecules already in preclinical/clinical phase tests, major gaps in the field and perspectives for the future of drug design for tropical diseases.


1   São Carlos Institute of Physics, University of São Paulo, Av. Joao Dagnone, 1100 – Jardim Santa Angelina, São Carlos 13563-120, Brazil


Link to article:   https://www.sciencedirect.com/science/article/pii/S0959440X19300272

Piper aduncum 24jul19

qua, 24 jul 2019

Publicado por

Authors:

Souza, Amauri Alves 1 ;  Vessecchi, Ricardo 2 ;  Castro‐Gamboa, Ian 1 ;  Furlan, Maysa 1


Abstract:

Natural 2H‐chromenes were isolated from the crude extract of Piper aduncum (Piperaceae) and analyzed by electrospray ionization tandem mass spectrometry (ESI‐MS/MS) applying collision‐induced dissociation. Density functional theory (DFT) calculations were used to explain the preferred protonation sites of the 2H‐chromenes based on thermochemical parameters, including atomic charges, proton affinity, and gas‐phase basicity. After identifying the nucleophilic sites, the pathways were proposed to justify the formation of the diagnostic ions under ESI‐MS/MS conditions. The calculated relative energy for each pathway was in good agreement with the energy‐resolved plot obtained from ESI‐MS/MS data. Moreover, the 2H‐chromene underwent proton attachment on the prenyl moiety via a six‐membered transition state. This behavior resulted in the formation of a diagnostic ion due to 2‐methylpropene loss. These studies provide novel insights into gas‐phase dissociation for natural benzopyran compounds, indicating how reactivity is correlated to the intrinsic acid‐base equilibrium and structural aspects, including the substitution pattern on the aromatic moiety. Therefore, these results can be applied in the identification of benzopyran derivatives in a variety of biological samples.


1  Universidade Estadual Paulista‐UNESP, Instituto de Química, Rua Professor Francisco Degni, 55, Araraquara, SP 14800‐900, Brazil

2  Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, SP 14040‐901, Brazil


Link to article:   https://onlinelibrary.wiley.com/doi/full/10.1002/jms.4378