Gracilin-Derivatives as Lead Compounds for Anti-inflammatory Effects

Gegunde, Sandra; Alfonso, Amparo; Albrecht, Eva; Alvariño, Rebeca; Botana, Luís M.

doi:10.1007/s10571-019-00758-5

Cited by 13 publications

(41 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the following experiments, the concentration of 1 μM of GraL, 0.1 μM of compounds 1 and 2 , and 0.2 μM of CsA were used. Since these concentrations have shown the greatest anti-inflammatory activity without compromising cell viability in previous experiments, both in T lymphocytes and glial cells ( 20 , 21 , 25 ). As shown in Figure 3A , the liberation of CypA was significantly reduced, when T cells were preincubated with compound 1 ( p < 0.05), compound 2 ( p < 0.05) or GraL ( p < 0.001).…”

Section: Resultsmentioning

confidence: 77%

“…Besides, they can modify transcriptional factors and reduce IL-2 release in activated T cells by blocking the activity of calcineurin phosphatase and inhibit CypA release ( 20 , 22 , 27 ). Moreover, it was recently reported that synthetic GraA-derivatives reduce the release of inflammatory mediators, avoid the translocation to the nucleus of inflammatory target proteins and promote antioxidative mechanisms in activated BV2 cells, likely through the CypA modulation ( 25 ). In the present paper, GraL and two GraA-derivatives, compounds 1 and 2 , with high CypA affinity, in the CsA range, were chosen.…”

Section: Discussionmentioning

confidence: 99%

“…Western blot was performed to determine the expression of CypA and CypB in the cytosol of T cells as previously described and as well as the expression of CypC in the Golgi apparatus and ER ( 25 ). In brief, to extract the cytosolic proteins, the pellet was suspended for 15 min in 100 μL of ice-cold hypotonic lysis, then 5 μL of Triton X-100 was added and centrifuged for 10 min at 4°C and 3000 rpm.…”

Section: Methodsmentioning

confidence: 99%

“…They showed kinetic equilibrium dissociation constants (K D ) values in the nanomolar range as measured by plasmon resonance experiments ( Table 1 ) ( 21 , 22 ). Moreover, these small molecules decrease pro-inflammatory mediators release, inhibit the calcineurin phosphatase activity, target the translocation of pro-inflammatory proteins and promote antioxidative mechanisms through CypA modulation ( 21 , 25 ). Therefore, they showed interesting anti-inflammatory capacities and are valuable tools to improve knowledge about the role of Cyps in inflammatory conditions.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cyclophilins A, B, and C Role in Human T Lymphocytes Upon Inflammatory Conditions

et al. 2021

Self Cite

View full text Add to dashboard Cite

Cyclophilins (Cyps) are a group of peptidyl-prolyl cis/trans isomerases that play crucial roles in regulatory mechanisms of cellular physiology and pathology in several inflammatory conditions. Their receptor, CD147, also participates in the development and progression of the inflammatory response. Nevertheless, the main function of Cyps and their receptor are yet to be deciphered. The release of CypA and the expression of the CD147 receptor in activated T lymphocytes were already described, however, no data are available about other Cyps in these cells. Therefore, in the present work intra and extracellular CypA, B and C levels were measured followed by induced inflammatory conditions. After activation of T lymphocytes by incubation with concanavalin A, both intra and extracellular Cyps levels and the CD147 membrane receptor expression were increased leading to cell migration towards circulating CypA and CypB as chemoattractants. When CypA was modulated by natural and synthetic compounds, the inflammatory cascade was avoided including T cell migration. Our results strengthen the relationship between CypA, B, and C, their receptor, and the inflammatory process in human T lymphocytes, associating CypC with these cells for the first time.

show abstract

Section: Resultsmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cyclophilins A, B, and C Role in Human T Lymphocytes Upon Inflammatory Conditions

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…A “lead compound”’ is defined as a chemical entity that has newly discovered promising therapeutic activity and into which further chemical modifications can be introduced to develop a new compound with optimized beneficial effects and minimized side effects [ 1 ]. Lead compounds have been used to develop new antimalarial [ 2 , 3 ], anti-inflammatory [ 4 , 5 ], anticancer [ 6 , 7 , 8 ], anti-platelet [ 9 , 10 , 11 ], and anticoagulant [ 12 , 13 ] agents. To transform these compounds for use as drug candidates in clinical trials, a number of requirements, such as stability, production with cGMP (current good manufacturing processes), identification of metabolic pathways and potential drug–drug interactions, toxicology assessments, and clinical development plans, must be met to establish a model pathway of drug development [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Lead Compounds in the Context of Extracellular Vesicle Research

Tran

2020

Pharmaceutics

View full text Add to dashboard Cite

Studies of small extracellular vesicles (sEVs), known as exosomes, have been flourishing in the last decade with several achievements, from advancing biochemical knowledge to use in biomedical applications. Physiological changes of sEVs due to the variety of cargos they carry undoubtedly leave an impression that affects the understanding of the mechanism underlying disease and the development of sEV-based shuttles used for treatments and non-invasive diagnostic tools. Indeed, the remarkable properties of sEVs are based on their nature, which helps shield them from recognition by the immune system, protects their payload from biochemical degradation, and contributes to their ability to translocate and convey information between cells and their inherent ability to target disease sites such as tumors that is valid for sEVs derived from cancer cells. However, their transport, biogenesis, and secretion mechanisms are still not thoroughly clear, and many ongoing investigations seek to determine how these processes occur. On the other hand, lead compounds have been playing critical roles in the drug discovery process and have been recently employed in studies of the biogenesis and secretion of sEVs as external agents, affecting sEV release and serving as drug payloads in sEV drug delivery systems. This article gives readers an overview of the roles of lead compounds in these two research areas of sEVs, the rising star in studies of nanoscale medicine.

show abstract

Terpenes extracted from marine sponges with antioxidant activity: a systematic review

Martignago

Soares-Silva

Parisi

et al. 2023

Nat. Prod. Bioprospect.

View full text Add to dashboard Cite

Marine biodiversity has emerged as a very promising resource of bioactive compounds and secondary metabolites from different sea organisms. The sponge’s secondary metabolites demonstrated various bioactivities and potential pharmacological properties. This systematic review of the literature focuses on the advances achieved in the antioxidant potential of marine sponges in vitro. The review was performed in accordance with PRISMA guidelines. The main inclusion criterion for analysis was articles with identification of compounds from terpene classes that demonstrate antioxidant activity in vitro. Searching in three different databases, two hundred articles were selected. After screening abstracts, titles and evaluating for eligibility of manuscripts 14 articles were included. The most performed analyzes to detect antioxidant activity were scavenging activity 2,2-diphenyl-1-picrylhydrazyl (DPPH) and measurement of intracellular reactive oxygen species (ROS). It was possible to identify 17 compounds of the terpene class with pronounced antioxidant activity in vitro. Scientific evidence of the studies included in this review was accessed by the GRADE analysis. Terpenes play an important ecological role, moreover these molecules have a pharmaceutical and industrial application. Graphical Abstract

show abstract

Gracilin-Derivatives as Lead Compounds for Anti-inflammatory Effects

Cited by 13 publications

References 43 publications

Cyclophilins A, B, and C Role in Human T Lymphocytes Upon Inflammatory Conditions

Cyclophilins A, B, and C Role in Human T Lymphocytes Upon Inflammatory Conditions

Lead Compounds in the Context of Extracellular Vesicle Research

Terpenes extracted from marine sponges with antioxidant activity: a systematic review

Contact Info

Product

Resources

About