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- ItemEmbargoResolution and absolute configuration of fargesin enantiomers(Wiley, 2024-11-06) Mestriner, Eloa R.; Lee, Eric Y. [UNIFESP]; Cunha, Camila L.; Sousa, Victor M.S. [UNIFESP]; Nascimento, Isabele R.; Batista Jr, Joao Marco [UNIFESP]; http://lattes.cnpq.br/4209224090500050Fargesin is an important bioactive furofuran lignan isolated from different plant species. Despite presenting potent biological activities, its stereochemical characterization has relied mostly on empirical correlations of optical rotation, an approach con- sidered risky that commonly leads to misassignments and error propagation. Additionally, the enantiomeric purity of fargesin isolates used for biological assays has not been previously investigated. Herein, we report the enantioresolution of a scalemic mixture of fargesin isolated from Aristolochia warmingii along with the first unambiguous determination of the absolute config- uration of each enantiomer by means of optical rotatory dispersion, as well as electronic and vibrational circular dichroism aided by quantum-chemical calculations.
- ItemEmbargoStereochemistry of natural products from vibrational circular dichroism(RSC, 2025-08-23) Batista, Andrea Nastri de Luca; Valverde, Alessandra Leda; Nafie, Laurence A.; Batista Junior, Joao Marcos [UNIFESP]; http://lattes.cnpq.br/4209224090500050Secondary metabolites from land and marine (micro)organisms have been at the focus of the drug discovery process for many years. One of the reasons for this success is nature’s incredible ability to create intricate molecular scaffolds. Such structural richness, however, makes the structural elucidation, and the absolute configuration assignment in particular, a challenging process. Vibrational circular dichroism (VCD) has emerged as one of the most reliable and versatile methods to unambiguously assign both the absolute configuration and conformations of chiral molecules in solution. Although VCD is no longer a curiosity in the field of molecular spectroscopy after 50 years since its first report, it is still underutilized by natural product chemists worldwide for varying reasons. Herein, we highlight the evolution of the application of VCD to natural product chemistry, focusing on its strengths as well as points that still need improvement. General guidelines for the correct application of VCD to stereochemical studies are also provided.
- ItemEmbargo7.1′,8.3′- and 7.3′,8.5′-Connected Bicyclo[3.2.1]octanoids and Oxabicyclo[3.2.2]nonane-Type Neolignans from Ocotea aciphylla: Structures and Absolute Configurations(ACS, 2024-02-23) Santos, Carlos Henrique Totini dos; Petrica, Edith Eunice Arthut; Batista, Andrea Nastri de Luca; Rodrigues, Edilene Delphino; Garcez, Walmir Silva; Albuquerque, Ana Carolina Ferreira de; Santos Jr, Fernando Martins dos; Batista Jr, Joao Marcos [UNIFESP]; Garcez, Fernanda Rodrigues; http://lattes.cnpq.br/4209224090500050The phytochemical investigation of the leaves and trunk bark of a specimen of Ocotea aciphylla collected in the southern portion of the Amazon forest led to the isolation of an oxabicyclo[3.2.2]nonane-type neolignan and 15 bicyclo[3.2.1]- octanoid neolignans, 14 of which are unreported compounds (2− 15), including one with an unusual oxidation pattern of the side chain at C-1′ and two rare 7.1′,8.3′-connected bicyclo[3.2.1]- octanoid derivatives. Their structures and relative configurations were determined by extensive spectrometric analysis based on 1D- and 2D-NMR spectroscopy and HRESIMS data, while their absolute configurations were unambiguously assigned using electronic and vibrational circular dichroism data assisted by density functional theory calculations. Additionally, known sesquiterpenes, phenylpropanoids, and phytosterols were also isolated
- ItemAcesso aberto (Open Access)Evaluation of the Anti‑biofilm Efficacy of Kyotorphin Derivatives and Biosafety Assessment: In Vitro and In Vivo Investigations Targeting Bacterial and Fungal Pathogens(Springer, 2024) Carvalho, Isabel Chaves Silva [UNIFESP]; Simões, Fernanda da Silva Seiffert [UNIFESP]; de Andrade, Vitor Martins [UNIFESP]; Tada, Dayane Batista [UNIFESP]; Heras, Montserrat; Bardají, Eduard; Lopes-Ferreira, Mônica; Castanho, Miguel Augusto Rico Botas; Conceição, Katia [UNIFESP]; http://lattes.cnpq.br/5360223612968931Kyotorphin (KTP) dipeptide (l-Tyrosine-l-Arginine) and their derivatives possess a multitude of functions, qualifying them as "multifunctional peptides." Considering the escalating bacterial resistance to antibiotics, antimicrobial peptides offer a promising road, forming the central focus of this current investigation. The effectiveness of KTP derivatives, GABA-KTPNH2 and Indol-KTP-NH2, were assessed for biofilm inhibition in bacterial and fungal strains. The viability of these derivatives was tested in fibroblasts and B16-F10-Nex2 cells. In vivo toxicity was evaluated using the model organisms Galleria mellonella and Danio rerio. Notably, both GABA-KTP-NH2 and Indol-KTP-NH2 derivatives effectively hindered biofilm formation in E. coli, S. pneumoniae, and C. krusei. In the G. mellonella model, the derivatives exhibited significant larval survival rates in toxicity tests, while in infection tests, they demonstrated efficient treatment against the evaluated microorganisms. Conversely, zebrafish assays revealed that Indol-KTP-NH2 induced substantial mortality rates in embryos after 72 and 96 h of exposure. Similarly, the GABA-KTP-NH2 derivative exhibited heightened lethality, noticeable at the 100 μM concentration after the same exposure periods. Importantly, toxicity assessments unveiled a relatively lower toxicity profile, coupled with a reduced potential for inducing abnormalities. These results highlight the necessity of employing a comprehensive approach that integrates diverse techniques to thoroughly assess toxicity implications.
- ItemAcesso aberto (Open Access)Mechanistic insights on the antibacterial action of the kyotorphin peptide derivatives revealed by in vitro studies and Galleria mellonella proteomic analysis(Elsevier, 2024) Andrade, Vitor Martins de [UNIFESP]; Oliveira, Vitor D M [UNIFESP]; Barcick, Uilla [UNIFESP]; Ramu , Vasanthakumar G.; Heras, Montserrat; Bardají , Eduard R.; Castanho, Miguel A.R.B.; Zelanis, André [UNIFESP]; Capella, Aline [UNIFESP]; Junqueira, Juliana C.; Conceição, Katia [UNIFESP]; http://lattes.cnpq.br/5360223612968931Objectives: The selected kyotorphin derivatives were tested to improve their antimicrobial and antibiofilm activity. The antimicrobial screening of the KTP derivatives were ascertained in the representative strains of bacteria, including Streptococcus pneumoniae, Streptococcus pyogenes, Escherichia coli and Pseudomonas aeruginosa. Methods: Kyotorphin derivatives, KTP-NH2, KTP-NH2-DL, IbKTP, IbKTP-NH2, MetKTP-DL, MetKTP-LD, were designed and synthesized to improve lipophilicity and resistance to enzymatic degradation. Peptides were synthesized by standard solution or solid-phase peptide synthesis and purified using RP-HPLC, which resulted in >95 % purity, and were fully characterized by mass spectrometry and 1H NMR. The minimum inhibitory concentrations (MIC) determined for bacterial strains were between 20 and 419 μM. The direct effect of IbKTP-NH2 on bacterial cells was imaged using scanning electron microscopy. The absence of toxicity, high survival after infection and an increase in the hemocytes count was evaluated by injections of derivatives in Galleria mellonella larvae. Proteomics analyses of G. mellonella hemolymph were performed to investigate the underlying mechanism of antibacterial activity of IbKTP-NH2 at MIC. Results: IbKTP-NH2 induces morphological changes in bacterial cell, many differentially expressed proteins involved in DNA replication, synthesis of cell wall, and virulence were up-regulated after the treatment of G. mellonella with IbKTP-NH2. Conclusion: We suggest that this derivative, in addition to its physical activity on the bacterial membranes, can elicit a cellular and humoral immune response, therefore, it could be considered for biomedical applications.