dianas 9(1) > Maqueda-Zelaya etal

dianas | Vol 9 Num 1 | marzo 2020 | e202003c02

New synthetic strategies for treatment of the renal disease: synthesis of peptide nucleic acids.

F Maqueda-Zelaya, V Miguel, J L Aceña, S Lamas, J J Vaquero

Facultad de Farmacia. Universidad de Alcalá.

a. francisco.maqueda@uah.es

V Congreso de Señalización Celular, SECUAH 2020.
16-18 de marzo, 2020. Universidad de Alcalá. Alcalá de Henares, Madrid. España.

Keywords: peptide nucleic acids; chronic kidney disease; miRNA; SPS

Abstract

Chronic kidney disease (CKD) is defined as the persistence of abnormalities in urine or kidney function damage caused by the loss of functional nephrons and usually derives in transplant or hemodialysis. CKD is a first-magnitude clinical and socio-economic problem, being necessary to develop therapies that improve the life quality of patients and decrease the economic costs of this disease without treatment. One of the most promising biomarkers are microRNAs (miRNAs), which can also be used as therapeutic tools. In this work, a new approach for CKD treatment is shown. It is based on the inhibition of the protein translation by the coupling of peptide nucleic acids (PNAs) to their complementary mRNA, producing its degradation. PNAs are more stable alternatives to the use of miRNAs, can be synthetized by SPS and modified easily to improve the insertion, as well as location inside cell membranes by the linkage of appropriate cell-penetrating peptides (CPPs) and fluorophores.

dianas 9(1) > González-Cofrade etal

dianas | Vol 9 Num 1 | marzo 2020 | e202003c01

Anti-inflammatory activity of labdanediol-derived diterpenes.

Laura González-Cofrade, Irene Cuadrado, Ana Estévez-Braun, Sonsoles Hortelano, Beatriz de las Heras

1. Departamento de Farmacología, Farmacognosia y Botánica, Facultad de Farmacia, Universidad Complutense de Madrid.  2. Instituto Universitario de Bio-Orgánica "Antonio González". Universidad de La Laguna, Tenerife, Spain.  3. Unidad de Terapias Farmacológicas, Instituto de Investigaciones en Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), Majadahonda, Madrid, España.

a. lagonz11@ucm.es

V Congreso de Señalización Celular, SECUAH 2020.
16-18 de marzo, 2020. Universidad de Alcalá. Alcalá de Henares, Madrid. España.

Keywords: Inflammation, diterpenes, macrophages

Abstract

Inflammation is a protective physiological response triggered by microbial infection or tissue injury with a key role in the pathogenesis of several chronic diseasease, due to the up-regulation and overproduction of proinflammatory mediators and the dysregulation of the NLRP3 inflammasome. Terpenes are bioactive natural products with great therapeutic potential. In this work, a series of ten novel labdanes derivatives (LB1-LB10) from the diterpene labdanediol isolated from Oxylobus glanduliferus was synthetized and evaluated for anti-inflammatory potential in lipopolysaccharide (LPS)-treated J774A.1 macrophages. Inhibitory effects of the non-toxic compounds on nitric oxide (NO) release were evaluated. Labdanediol derivative LB5 was selected as the most active inhibitor (IC50= 10 µM). LB5 also significantly inhibited the protein expression of Nitric Oxide Synthase-2 (NOS-2) and Cyclooxygenase-2 (COX-2) enzymes and the gene expression at the transcriptional level of NOS-2, COX-2 and inflammatory cytokines (IL-6, TNFα). Regulation of NLRP3 inflammasome pathway seems not to be involved in the anti-inflammatory activity of these compounds, as IL-1β levels in LPS/ATP-stimulated macrophages were not significantly reduced by treatment with these derivatives. In summary, we have identified a novel labdanediol derivative (LB5) with potential anti-inflammatory activity so it can be considered as a promising starting point for the development of new anti-inflamatory agents. Further experiments will be performed to elucidate the molecular mechanisms involved.