Abstract:

Heterocyclic compounds are cornerstone for active pharmaceutical ingredients. Among heterocycles, isoindoline core occupies special place as ten commercial bioactive compounds/drugs contain this skeleton decorated with several functional groups required for optimal receptor binding. These drugs are employed for indications such as multiple myeloma, leukemia, inflammation, hypertension, edema, obesity, and insect control. This review presents pharmacological activities, mechanisms of action and chemical syntheses of these commercial bioactive molecules/drugs.

Abstract:

Determining the values of various properties for new bioinks for 3D printing is a very important task in the design of new materials. For this purpose, a large number of experimental works have been consulted and a database with >1200 bioprinting tests has been created. These tests cover different combinations of conditions in terms of print pressure, temperature, and needle values, for example. These data are difficult to deal with in terms of determining combinations of conditions to optimize the tests and to analyze new options. The best model presented has values of specificity = Sp (%) = 88.4, sensitivity = Sn (%) = 86.2 in training series and Sp (%) = 85.9, Sn (%) = 80.3 in external validation series. This model uses operators based on perturbation theory in order to analyze the complexity of the data. The performance of the model has been compared with neural networks with very similar results. This tool could be easily applied to predict the properties of in silico bioprinting assays.

Abstract: As an appealing approach for discovering novel leads, the key advantage of de novo drug design lies in its ability to explore a much broader dimension of chemical space, without being confined to the knowledge of existing compounds. So far many generative models have been described in the literature, which have completely redefined the concept of de novo drug design. However, many of them lack practical value for real-world drug discovery. In this work, we have developed a graph-based generative model within a reinforcement learning framework, namely METEOR (Molecular Exploration Through multiplE-Objective Reinforcement). The backend agent of METEOR is based on the well-established GCPN model. To ensure the overall quality of the generated molecular graphs, we implemented a set of rules to identify and exclude undesired substructures. Importantly, METEOR is designed to conduct multi-objective optimization, i.e. simultaneously optimizing binding affinity, drug-likeness, and synthetic accessibility of the generated molecules under the guidance of a special reward function. We demonstrate in a specific test case that, without prior knowledge of true binders to the chosen target protein, METERO generated molecules with superior properties compared to those in the ZINC 250k data set. In conclusion, we have demonstrated the potential of METERO as a practical tool for generating rational drug-like molecules in the early phase of drug discovery.

Abstract: This study evaluated the stability and reusability of amino-functionalized nanocellulose aero-gels as CO₂ adsorbent materials. The modified aerogels, synthesized via a controlled silylation using N-[3-(trimethoxysilyl) propyl] ethylenediamine (DAMO), demonstrated excellent thermal stability up to 250°C (TGA) and efficient CO₂ adsorption through chemisorption, which was the main adsorption mechanism. The performance of the aerogels was assessed using both, adsorp-tion isotherms and the decay pressure technique, revealing that CO₂ adsorption capacity in-creased with higher amino group loading (4.62, 9.24, and 13.87 mmol of DAMO). At 298 K and 4 bar, CO₂ adsorption capacity increased proportionally with the amino group concentration, reaching values of 3.17, 5.98, and 7.86 mmol of CO₂ g-1 polymer, respectively. Furthermore, over 20 adsorption/desorption cycles, the aerogels maintained 95% CO₂ desorption at ambient tem-perature, indicating their potential for industrial use. These findings highlight the aerogels suitability as stable, reusable materials for large scale CO₂ capture and storage technologies.

Abstract:

Porous organic polymers (POPs), based on polysulfone (PSU) and covalently linked zirconium-organic moieties have been applied for the first time to Arsenic removal in wastewater. The synthesis involved anchoring a synthon molecule onto PSU, followed by MOF assembly and subsequent quaternization (QA) with trimethylamine (TMA). Two samples Zr-POP and Zr-POP-QA are characterized by NMR, FTIR, and titration. The efficiency of As uptake is revealed by ICP. The study is carried out at different pH (3, 7, and 12) to vary the charge of Zr-organic moieties and the charge of arsenite and arsenate species. Two concentrations (0.5 and 1 mM) of As (III) and As (V) are used. The results show that Zr-POP at pH 3 has a removal efficiency (RE%) of 77% for As (V), in agreement with the positive charge present in the Zr-framework at this pH. At neutral pH the As (III) sorption is also relevant. Zr-POP-QA at pH 12 shows, thanks to the positive charge on the ammonium moieties, a RE% of As (III) equal to 35%. The kinetic of processes, performed on the most promising system, i.e. Zr-POP at pH 3 for As(V), shows a plateau already after 8 hours with a second-order law. The regeneration of the material is also evaluated. According to the results, these materials are serious candidates in the removal of heavy metals in wastewater.

Abstract: Hybrid nanocomposites incorporating multiple fillers are gaining significant attention due to their ability to enhance material performance, offering superior properties compared to traditional monophase systems. This study investigates hybrid epoxy-based nanocomposites reinforced with multi-walled carbon nanotubes (MWCNTs) and graphene nanosheets (GNs), introduced at two different weight concentrations of the mixed filler, i.e. 0.1 wt% and 0.5 wt%, which are, respectively, below and above the Electrical Percolation Threshold (EPT) for the two binary polymer composites that solely include one of the two nanofillers, with varying MWCNTs:GNs ratios. Mechanical properties, such as contact depth, hardness, and reduced modulus, were experimentally assessed via nanoindentation, while morphological analysis supported the mechanical results. A Design of Experiments (DoE) approach was utilized to evaluate the influence of filler concentrations on the composite's mechanical performance, and Response Surface Methodology (RSM) was applied to derive a mathematical model correlating the filler ratios with key mechanical properties. The best and worst-performing formulations, based on hardness and contact depth results, were further investigated through detailed numerical simulations using a multiphysics software. After validation considering experimental data, the simulations provided additional insights into the mechanical behavior of the hybrid composites. This work aims to contribute to the knowledge base on hybrid composites and promote the use of computational modeling techniques for optimizing the design and mechanical performance of advanced materials.

Abstract: This research explores the synthesis and application of carbon-based adsorbents derived from olive stones and almond shells as low-cost biomass precursors through carbonization at 600°C combined with chemical activation using KOH, H3PO4 and ZnCl2 with carbon/activating agent (C/A) ratios of 1:2 and 1:4 (w/w) at 850°C for the removal of Cu2+ and Pb2+ ions from aqueous solutions. The carbons produced were characterized using different techniques including SEM-EDX, FTIR, XRD, BET analysis, CHNS elemental analysis and point of zero charge determination. Batch-mode adsorption experiments were carried out at adsorbent doses of 2 and 5 g L-1, initial metal concentrations of 100 and 500 mg L-1 and natural pH (around 5) with agitation at 350 rpm and 25°C for 24 h. KOH-activated carbons, especially at a 1:4 (w/w) ratio, exhibited superior adsorption performance mainly due to their favorable surface characteristics and functionalities. The greatest adsorption efficiency reached 100% (101.41-101.68 mg g-1) for Pb2+ at 500 mg L-1 and 5 g L-1 dosage, and 84.63-86.29% (41.69-42.52 mg g-1) for Cu2+ at 100 mg L-1 and 2 g L-1 dosage. The results of this study will help advance knowledge in the design and optimization of adsorption processes for heavy metal removal, benefiting industries seeking green technologies to mitigate environmental pollution.

Abstract: In this article we describe the synthesis of a β-truxinate from the [2+2] dimerization of methyl 4-nitrocinnamate and its isomerization by different bases using liquid-assisted grinding (LAG) technique. With this methodology it is possible to obtain the corresponding ζ- and δ-truxinates in short reaction times and with only small amounts of solvent. Furthermore, it is possible to steer the process towards the preferential formation of ζ- or δ-truxinate depending on the base used.

Abstract: Developing new biomolecule-drug conjugates as prodrugs is a promising area for natural products and pharmaceutical chemistry. Herein, a cholesterol-doxorubicin (Chol-DOX) conjugate was synthesized using cholesteryl-4-nitrophenolate as a facile, stable, and controllable activated ester. This approach offers an alternative to the conventional HCl-emitting cholesteryl chloroformate method, semi-empirical theoretical calculations showed that cholesteryl-4-nitrophenolate exhibits moderate reactivity, higher thermodynamic stability, and a lower HOMO-LUMO energy gap compared to cholesteryl chloroformate, suggesting cholesteryl-4-nitrophenolate could be used as a more controllable acylating agent. The structure of synthesized Chol-DOX conjugate was characterized using NMR and MS techniques. Biological properties of the Chol-DOX were analyzed with the comparison of theoretical and experimental data. This work provided a facile and controllable method to synthesize natural lipid-DOX prodrug and offered an in-depth data analysis of the related biological properties.

Abstract: Considering all our previous experience in the design of new cholinesterase inhibitors, especially resveratrol analogs, in this research, the basic stilbene skeleton was used as a structural unit for new carbamates. Inhibitory activity was tested toward the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by newly prepared carbamates 1–13. In the tested group of compounds, the leading inhibitors were 1 and 7, which achieved excellent selective inhibitory activity for BChE with IC50 values of 0.12 ± 0.09 μM and 0.38 ± 0.01 μM, respectively. Both were much more active than standard inhibitor galantamine against BChE. Molecular docking of the most promising inhibitor candidates, compounds 1 and 7, revealed that stabilizing interactions between the active site residues of BChE and the ligands involve π-stacking, alkyl-π interactions, and, when the carbamate orientation allows, H-bond formation. MD analysis confirmed the stability of the obtained complexes. Some bioactive resveratrol-based carbamates displayed complex-forming capabilities with Fe3+ ions as metal centers. Spectrophotometric investigation indicated that they coordinate one or two metal ions, which is in accordance with their chemical structure, offering two binding sites: an amine and a carboxylic group in the carbamate moiety. Based on all obtained in silico, experimental, and computational results on biological activity in the present work, new carbamates 1 and 7 represent potential selective BChE inhibitors as new therapeutics for neurological disorders.