Norditerpenoids with selective anti-cholinesterase activity from the roots of Perovskia atriplicifolia Benth

Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer's disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of diterpenoids from Perovskia atriplicifolia and other Lamiaceae species. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition by the three new natural compounds-(1R,15R)-1-acetoxycryptotanshinone (1), (1R)-1-acetoxytanshinone IIA (2), and (15R)-1-oxoaegyptinone A (3)-as well as, new for this genus, isograndifoliol (4) were assessed. Three of these compounds exhibited profound inhibition of butyrylcholinesterase (BChE) and much weaker inhibition of acetylcholinesterase (AChE). All compounds (1-4) selectively inhibited BChE (IC(50) = 2.4, 7.9, 50.8, and 0.9 µM, respectively), whereas only compounds 3 and 4 moderately inhibited AChE (IC(50) 329.8 µM and 342.9 µM). Molecular docking and in silico toxicology prediction studies were also performed on the active compounds. Natural oxygenated norditerpenoids from the traditional Central Asian medicinal plant P. atriplicifolia are selective BChE inhibitors. Their high potential makes them useful candidate molecules for further investigation as lead compounds in the development of a natural drug against dementia caused by neurodegenerative diseases

Cisplatin cytotoxicity: A theoretical study of induced mutations

We investigate possible mutations in the genetic code induced by cisplatin with an approach combining molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Specifically, the impact of platination on the natural tautomeric equilibrium in guanine-cytosine (GC) base pairs is assessed to disclose the possible role played by non-canonical forms in anti-tumour activity. To obtain valuable predictions, the main interactions present in a real DNA environment, namely hydration and stacking, are simultaneously taken into account. According to our results, the Pt-DNA adduct promotes a single proton transfer reaction in GC in the DNA sequence AGGC. Such rare tautomers might play an important role in the cisplatin biological activity since they meet the stability requirements necessary to promote a permanent mutation. This journal is © the Owner Societies 2012.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Selective semi-hydrogenation of internal alkynes catalyzed by Pd–CaCO3 clusters

The de-novo synthesis of soluble or solid-supported Pd-(CaCO) clusters (n = 2–13) and their high catalytic activity for the semi-hydrogenation of internal alkynes compared to terminal alkynes, is presented. Mechanistic studies show that this reactivity, i.e. internal alkynes more reactive than terminal alkynes, comes from the higher electrophilicity of the Pd-(CaCO) cluster compared to the nanoparticulated Lindlar catalyst, which unveils the advantages of isolating the minimum catalytic unit of a solid catalyst. Translating solid active sites into soluble catalysts turns around the classical approach and constitutes a paradigmatic shift in catalyst design.This work is part of the projects PID2020–115100GB–I00 and PID2019–107578GA–I00, both funded by MCIN/AEI/10.13039/501 100011033MICIIN, and ‘‘La Caixa” Foundation grant (ID 100010434), code LCF/BQ/DI19/11730029

Cyclic metal(oid) clusters control platinum-catalysed hydrosilylation reactions: From soluble to zeolite and MOF catalysts

The Pt-catalysed addition of silanes to functional groups such as alkenes, alkynes, carbonyls and alcohols, i.e. the hydrosilylation reaction, is a fundamental transformation in industrial and academic chemistry, often claimed as the most important application of Pt catalysts in solution. However, the exact nature of the Pt active species and its mechanism of action is not well understood yet, particularly regarding regioselectivity. Here, experimental and computational studies together with an ad hoc graphical method show that the hydroaddition of alkynes proceeds through Pt-Si-H clusters of 3-5 atoms (metal(oid) association) in parts per million amounts (ppm), which decrease the energy of the transition state and direct the regioselectivity of the reaction. Based on these findings, new extremely-active (ppm) microporous solid catalysts for the hydrosilylation of alkynes, alkenes and alcohols have been developed, paving the way for more environmentally-benign industrial applications. This journal isFinancial support by MINECO through the Severo Ochoa program (SEV-2016-0683), Excellence program (CTQ 2017-86735-P and CTQ 2017-87974-R) and Retos Col. (RTC-2017-6331-5) is acknowledged. E. P. acknowledges the financial support of the European Research Council under the European Union's Horizon 2020 research and innovation program/ERC Grant Agreement No. 814804, MOF-reactors. M. A. R.-C. thanks ITQ for the concession of a contract and J. O. M. thanks the Juan de la Cierva program for the concession of a contract. We thank V. B. dLL. and N. G. G. for performing degree projects in the ITQ labs. This research was partially supported by the supercomputing infrastructure of Poznan Supercomputing Center. The Electron Microscopy Service of the UPV is also acknowledged

Cytotoxic sub-nanometer aqueous platinum clusters as potential antitumoral agents

Ligand-free sub-nanometer metal clusters (MCs) of Pt, Ir, Rh, Au and Cu, are prepared here in neat water and used as extremely active (nM) antitumoral agents for HeLa and A2870 cells. The preparation just consists of adding the biocompatible polymer ethylene-vinyl alcohol (EVOH) to an aqueous solution of the corresponding metal salt, to give liters of a MC solution after filtration of the polymer. Since the MC solution is composed of just neat metal atoms and water, the intrinsic antitumoral activity of the different sub-nanometer metal clusters can now fairly be evaluated. Pt clusters show an IC of 0.48 μM for HeLa and A2870 cancer cells, 23 times higher than that of cisplatin and 1000 times higher than that of Pt NPs, and this extremely high cytotoxicity also occurs for cisplatin-resistant (A2870 cis) cells, with a resistance factor of 1.4 (IC = 0.68 μM). Rh and Ir clusters showed an IC ∼ 1 μM. Combined experimental and computational studies support an enhanced internalization and cytotoxic activation.This work was supported by MINECO (Spain, Projects CTQ 2017-86735-P [AEI/FEDER, UE], PID2020-115010RB-I00, BEAGAL 18/00211, MAT2017-87579-R, IJC2018-036514-I and SEV-2016-0683). Financial support by the project PID2020-115100GB-I00 (funded by Spanish MCIINN, MCIN/AEI/10.13039/501100011033MICIIN) is acknowledged

Removal and toxicity evaluation of a diverse group of drugs from water by a cyclodextrin polymer/pulsed light system

The presence of pharmaceutical compounds (PhCs) in the effluents of wastewater treatment plants (WWTPs) is an ecological concern. The issue could be alleviated by trapping those substances by cyclodextrin (CD) polymers or photolyzing them by pulsed light (PL). Consequently, a sequential CD polymer/PL system was tested for the removal of PhCs. Firstly, a survey detected the presence of recurrent PhCs in the effluents of local WWTPs. Then, pure water was spiked with 21 PhCs, 100 μg/L each one. The three-dimensional network provides amphiphilic features to the CD polymer that reduced the pollutant concentration by 77 %. Sorption involves a plead of physical and chemical mechanisms hindering the establishment of a general removal model for all compounds. The performed simulations hint that the retention capacity mainly correlates with the computed binding energies, so that theoretical models are revealed as valuable tools for further improvements. The complementary action of PL rose the elimination to 91 %. The polymer can be reused at least 10 times for ibuprofen (model compound) removal, and was able to eliminate the ecotoxicity of an ibuprofen solution. Therefore, this novel sequential CD polymer/PL process seems to be an efficient alternative to eliminate PhCs from wastewater.This work was supported by the project LIFE16ENV/ES/000169, "Validation of adsorbent materials and advanced oxidation techniques to remove emerging pollutants in treated wastewater". The authors also acknowledge SCIEX for providing the loan instrument LC/HRMS QTOF X500R. This work used computational resources from the Plataforma Andaluza de Bioinformática at the Universidad de Málaga and the supercomputing infrastructure of Poznan Supercomputing Center.Peer reviewe