Chemical composition and biological activity of Capparis spinosa L. from Lipari Island

Several plants belonging to the genus Capparis are the focus of growing interest due to their singular nutritional and medicinal properties. In the present study, flower bud samples from C. spinosa L. (Lipari Island, Italy) were subjected to decoction, Soxhlet, and microwave extraction techniques and the individual extracts investigated to better characterize the phytochemical and antioxidant profiles of the plant. Total phenolic and flavonoid amounts, phenolic composition, radical scavenging as well as reductive and metal chelating properties were determinated by well-established chemical and analytical procedures. Furthermore, cholinesterase inhibitory effects were evaluated by Ellman's method. Fatty acid percentage and essential oil composition were also detected by GC and GC-MS techniques respectively. Rutin was found to be the major component in the studied extracts. The Soxhlet extract exhibited the strongest radical scavenging and reductive activities as compared to the other extracts, most probably due to the highest concentration of phenolics, especially rutin. The best cholinesterase inhibitory effect was observed in the microwave extract. Palmitic acid was the most abundant fatty acid in the studied oil, whereas docosane was the major volatile compound in the essential oil. Present data corroborate the multipurpose potential of C. spinosa for designing bio-based drug formulations or functional applications. (c) 2018 SAAB. Published by Elsevier B.V. All rights reserved

Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge

d-Pen2,d-Pen5 enkephalin (DPDPE) is one of the most selective synthetic peptide agonists targeting the delta-opioid receptor. Three cyclic analogues of DPDPE containing a xylene bridge in place of disulfide bond have been synthesized and fully characterized as opioid receptors agonists. The in vitro activity was investigated showing a good affinity of 7a-c for mu- and delta-receptors. In vivo biological assays revealed that 7b is the most potent analogue with the ability to maintain high level of analgesia from 15 to 60 min following intracerebroventricular (i.c.v.) administration, whereas DPDPE was slightly active until 45 min. Compound 7b induced long lasting analgesia also after subcutaneous administration, whereas DPDPE was inactive

Design, synthesis and biological profile of mixed opioid agonist/N-VGCC blocker peptides

In this paper we reported the synthesis and the in vitro and the in vivo biological evaluation of linear pseudo-peptides incorporating the N-VGCC blocker tripeptide Phe-NMe-Leu-Tyr(OBz)-NtBu and the biphalin pharmacophore Tyr-D-Ala-Gly-Phe. The novel sequences have been designed by using amino acids of different length to join the two pharmacophores and explore the structure-activity relationships of the novel compounds

Novel Fubinaca/Rimonabant hybrids as endocannabinoid system modulators

The discovery of novel modulators of the cannabinoid system is a current topic in medicinal chemistry. In this paper, we report nine novel carboxamides designed as hybrids of Fubinaca family compounds and Rimonabant. These hybrids were obtained by linking the 1-benzyl-2,5-dichloroindazole-3-carboxylic acid to different amino acids bearing a hydrophobic side chain and three different C-terminus. The new chemical entities were tested in vitro to evaluate their bioactivity by means of receptor binding assays and [S-35]GTPS stimulation assays to reveal their affinity and potency. We found that all compounds were able to bind to the cannabinoid receptors in the low nanomolar range with a marked selectivity towards the CB1 cannabinoid receptor. Some of them are full agonists, whereas the others act as partial agonists. These molecules could be potentially used as anti-obesity agents, antiemetic and analgesics

Cyclic biphalin analogues with a novel linker lead to potent agonist activities at mu, delta, and kappa opioid receptors

In an effort to improve biphalin's potency and efficacy at the mu-( MOR) and delta-opioid receptors (DOR), a series of cyclic biphalin analogues 1-5 with a cystamine or piperazine linker at the C-terminus were designed and synthesized by solution phase synthesis using Boc-chemistry. Interestingly, all of the analogues showed balanced opioid agonist activities at all opioid receptor subtypes due to enhanced.-opioid receptor (KOR) activity. Our results indicate that C-terminal flexible linkers play an important role in KOR activity compared to that of the other cyclic biphalin analogues with a hydrazine linker. Among them, analogue 5 is a potent (Ki= 0.27, 0.46, and 0.87 nM; EC50= 3.47, 1.45, and 13.5 nM at MOR, DOR, and KOR, respectively) opioid agonist with high efficacy. Based on the high potency and efficacy at the three opioid receptor subtypes, the ligand is expected to have a potential synergistic effect on relieving pain and further studies including in vivo tests are worthwhile.University of Arizona, United States [UA15-178]; U.S. Public Health Services, NIH; NIDA [P01DA006248]24 month embargo; published online: 26 May 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Five- and Six-Membered Nitrogen-Containing Compounds as Selective Carbonic Anhydrase Activators

It has been proven that specific isoforms of human carbonic anhydrase (hCA) are able to fine-tune physiological pathways connected to signal processing, and that decreased CAs expression negatively influences cognition, leading to mental retardation, Alzheimer’s disease, and aging-related cognitive dysfunctions. For this reason, a small library of natural and synthetic nitrogen containing cyclic derivatives was assayed as activators of four human isoforms of carbonic anhydrase (hCA I, II, IV and VII). Most of the compounds activated hCA I, IV and VII in the micromolar range, with KAs ranging between 3.46 and 80.5 μM, whereas they were not active towards hCA II (KAs > 100 μM). Two natural compounds, namely l-(+)-ergothioneine (1) and melatonin (2), displayed KAs towards hCA VII in the nanomolar range after evaluation by a CO2 hydration method in vitro, showing a rather efficient and selective activation profile with respect to histamine, used as a reference compound. Corroborated with the above in vitro findings, a molecular modelling in silico approach has been performed to correlate these biological data, and to elucidate the binding interaction of these activators within the enzyme active site

Investigation on the stability of new biologically active thiosemicarbazone-derived compounds by a validated HPLC-PDA method

New Chemical Entities (NCEs) could be generally exposed to several stress conditions of hydrolysis, oxidation, photolysis and thermal degradation in order to better characterize the compounds and to know if the degradation processes lead to generate undesired (or toxic) products