The design, synthesis, and anti-inflammatory evaluation of a drug-like library based on the natural product valerenic acid

Abstract

The plant natural product, valerenic acid (1) was chosen as a desirable scaffold for the generation of a novel screening library due to its drug-like physicochemical parameters (such as LogP, hydrogen bond donor/acceptor counts, and molecular weight). An 11-membered amide library (2-12) was subsequently generated using parallel solution-phase synthesis and Ghosez's reagent. The chemical structures of all semi-synthetic analogues (2-12) were elucidated following analysis of the NMR, MS, UV and IR data. The structures of compounds 8 and 11 were also confirmed by X-ray crystallographic analysis. All library members were evaluated for their ability to inhibit the release of IL-8 and TNF-α. Six analogues showed moderate activity in the IL-8 assay with IC values of 2.8-8.3μM, while none of the tested compounds showed any significant effect on inhibiting TNF-α release.

Using UHPLC-MS Profiling for the Discovery of New Dihydro-β-Agarofurans from Australian Celastraceae Plant Extracts

“…Other Celastraceae samples that were prioritised for large-scale extraction and isolation studies will be investigated in the future. The pure compounds reported in this paper will be added to the Davis Open-Access Compound Library which is housed at Compounds Australia, Griffith University [19,22,23,24,25] and will be tested in various bioassays in the future. It is worth mentioning and well-known that the chemical profile of a plant can vary due to different geographical locations and collection seasons; however, even though this research utilised only Queensland Celastraceae plants, the UHPLC-MS method developed here should be applicable to the chemical profiling of any plant sample.…”

Valeriana pilosa Ruiz & Pav.: una revisión de usos tradicionales, fitoquímica y farmacología Valeriana pilosa Ruiz & Pav.: a review of traditional uses, phytochemistry and pharmacology

“…El consumo tradicional de la raíz en extractos acuosos (infuso o decocto) contiene ácido gaminobutírico, que estimula al receptor GABA y genera el efecto ansiolítico y sedativo, actividades farmacológicas principales de estas especies (Wills et al 2000). Además, estudios posteriores in vivo e in vitro indican que estas actividades son por la estimulación del ácido valerénico y valepotriatos, que son reconocidos como moduladores alostéricos, al receptor GABAA (Becker et al 2014, Büchi et al 1960, Egbewande et al 2017, Felgentreff et al 2012, específicamente, a través de su subunidad β3 (Benke et al 2009, Khom et al 2007, Khom et al 2010, Khom et al 2016. El ácido valerénico se considera de mayor relevancia debido a su relación con la actividad ansiolítica en las especies del género Valeriana, y por encontrarse en mayor proporción.…”

Synthesis of bilocularin A carbamate derivatives and their evaluation as leucine transport inhibitors in prostate cancer cells

“…We have also reported the most potent inhibitor of LAT (bilocularin G, IC50 = 2.5 µM) to date, which was isolated from the roots of M. bilocularis (Wibowo et al, 2018). These discoveries led us to further explore the potential of dihydro-β-agarofurans as LAT inhibitors by designing a semi-synthetic library based on this unique chemotype (Barnes et al, 2012;Choomuenwai et al, 2012;Davis et al, 2007;Egbewande et al, 2019Egbewande et al, , 2018Egbewande et al, , 2017Kumar et al, 2015).…”