Antiviral efficacy of heparan sulfate and enoxaparin sodium against SARS-CoV-2.

As the world transitions from the acute phase of the COVID-19 pandemic caused by SARS-CoV-2, the scientific community continues to explore various therapeutic avenues to control its spread and mitigate its ongoing effects. Among the promising candidates are heparan sulfate (HS) and enoxaparin (EX), which have emerged as potential virus inhibitors. HS, a type of glycosaminoglycan, plays a prominent role in the attachment of the virus to host cells.

Learning Strategies from Nature's Blueprint to Cyclic Carbonate Synthesis.

Nature is a remarkable source of inspiration for developing sustainable and eco-friendly synthetic procedures. In recent years, the synthesis of cyclic carbonates has garnered significant attention due to their versatile applications in various fields, including materials science, pharmaceuticals, and green chemistry. Drawing inspiration from nature, researchers have explored innovative synthetic routes that mimic biological processes to produce cyclic carbonates efficiently and sustainably.

Polyvinylimidazole-Based Cryogel as an Efficient Tool for the Capture and Release of Oleuropein in Aqueous Media.

A polyvinylimidazole-based cryogel is presented as a pioneering solution for efficient extraction and release of partially water-soluble polyphenols from olive byproducts. Specifically, oleuropein was used as model molecule to evaluate its recovery from water. The material merges the properties of interconnected cryogel structure in adsorbing molecules via fast diffusion flux, with the strong electrostatic interactions acted by imidazole moiety.

Tetrazine-trans-cyclooctene ligation: Unveiling the chemistry and applications within the human body.

Bioorthogonal reactions have revolutionized chemical biology by enabling selective chemical transformations within living organisms and cells. This review comprehensively explores bioorthogonal chemistry, emphasizing inverse-electron-demand Diels-Alder (IEDDA) reactions between tetrazines and strained dienophiles and their crucial role in chemical biology and various applications within the human body. This highly reactive and selective reaction finds diverse applications, including cleaving antibody-drug conjugates, prodrugs, proteins, peptide antigens, and enzyme substrates.

Synthesis, Characterisation, and In Vitro Evaluation of Biocompatibility, Antibacterial and Antitumor Activity of Imidazolium Ionic Liquids.

In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial fields. This study aims to synthetise two series of methylimidazolium ILs bearing long alkyl chain in their cations (C9, C10, C12, C14, C16, C18, C20) and with tetrafluoroborate (BF) and the 1,3-dimethyl-5-sulfoisophthalate (DMSIP) as counter ions.

TiO/Loofah-Halloysite Bio-Hybrid Composites as Efficient Systems for VOCs Removal.

Volatile organic compounds (VOCs), recognized as hazardous air contaminants, prompt the exploration of sustainable air purification methods. Solar photocatalytic oxidation emerges as a promising solution, utilizing semiconductor photocatalysts like titanium dioxide (TiO). However, the raw material crisis necessitates reduced TiO usage, leading to investigations into TiO modification techniques.

γ-Cyclodextrins as Supramolecular Reactors for the Three-component Aza-Darzens Reaction in Water.

In recent decades, many efforts have been devoted to studying reactions catalyzed in nanoconfined spaces. The most impressive aspect of catalysis in nanoconfined spaces is that the reactivity of the molecules can be smartly driven to disobey classical behavior. A green and efficient three-component aza-Darzens (TCAD) reaction using a catalytic amount of γ-cyclodextrins (CDs) in water has been developed to synthesize N-phenylaziridines.

Discovery of first novel sigma/HDACi dual-ligands with a potent in vitro antiproliferative activity.

Designing and discovering compounds for dual-target inhibitors is challenging to synthesize new, safer, and more efficient drugs than single-target drugs, especially to treat multifactorial diseases such as cancer. The simultaneous regulation of multiple targets might represent an alternative synthetic approach to optimize patient compliance and tolerance, minimizing the risk of target-based drug resistance due to the modulation of a few targets. To this end, we conceived for the first time the design and synthesis of dual-ligands σR/HDACi to evaluate possible employment as innovative candidates to address this complex disease.

Total Bio-Based Material for Drug Delivery and Iron Chelation to Fight Cancer through Antimicrobial Activity.

Bacterial involvement in cancer's development, along with their impact on therapeutic interventions, has been increasingly recognized. This has prompted the development of novel strategies to disrupt essential biological processes in microbial cells. Among these approaches, metal-chelating agents have gained attention for their ability to hinder microbial metal metabolism and impede critical reactions.

New Insights into the Opioid Analgesic Profile of -(-)--Normetazocine-derived Ligands.

In this work, we report on the in vitro and in vivo pharmacological properties of LP1 analogs to complete the series of structural modifications aimed to generate compounds with improved analgesia. To do that, the phenyl ring in the -substituent of our lead compound LP1 was replaced by an electron-rich or electron-deficient ring and linked through a propanamide or butyramide spacer at the basic nitrogen of the (-)---normetazocine skeleton. In radioligand binding assays, compounds and were found to display nanomolar binding affinity for the μ opioid receptor (MOR) (K = 5.

Computer-Assisted Design of Peptide-Based Radiotracers.

In medical imaging, techniques such as magnetic resonance imaging, contrast-enhanced computerized tomography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT) are extensively available and routinely used for disease diagnosis. PET probes with peptide-based targeting are typically composed of small peptides especially developed to have high affinity and specificity for a range of cellular and tissue targets. These probes' key benefits include being less expensive than traditional antibody-based PET tracers and having an effective chemical modification process that allows them to be radiolabeled with almost any radionuclide, making them highly appealing for clinical usage.

Heparan Sulfate and Enoxaparin Interact at the Interface of the Spike Protein of HCoV-229E but Not with HCoV-OC43.

It is known that the spike protein of human coronaviruses can bind to a secondary receptor, or coreceptor, to facilitate the virus entry. While HCoV-229E uses human aminopeptidase N (hAPN) as a receptor, HCoV-OC43 binds to 9--acetyl-sialic acid (9--Ac-Sia), which is linked in a terminal way to the oligosaccharides that decorate glycoproteins and gangliosides on the surface of the host cell. Thus, evaluating the possible inhibitory activity of heparan sulfate, a linear polysaccharide found in animal tissues, and enoxaparin sodium on these viral strains can be considered attractive.

Steered Molecular Dynamics Simulations Study on FABP4 Inhibitors.

Ordinary small molecule de novo drug design is time-consuming and expensive. Recently, computational tools were employed and proved their efficacy in accelerating the overall drug design process. Molecular dynamics (MD) simulations and a derivative of MD, steered molecular dynamics (SMD), turned out to be promising rational drug design tools.

Portable Nanocomposite System for Wound Healing in Space.

It is well known that skin wound healing could be severely impaired in space. In particular, the skin is the tissue at risk of injury, especially during human-crewed space missions. Here, we propose a hybrid system based on the biocompatible poly 2-hydroxyethyl methacrylate (pHEMA) to actively support a nanocontainer filled with the drug.

Design, synthesis, in vitro evaluation, and molecular modeling studies of N-substituted benzomorphans, analogs of LP2, as novel MOR ligands.

6,7-Benzomorphans have been investigated in medicinal chemistry for developing new drugs. This nucleus could be considered a versatile scaffold. The physicochemical properties of benzomorphan N-substituent are crucial in achieving a definite pharmacological profile at opioid receptors.

1,2-Dibenzoylhydrazine as a Multi-Inhibitor Compound: A Morphological and Docking Study.

In the framework of the multitarget inhibitor study, we report an in silico analysis of 1,2-dibenzoylhydrazine (DBH) with respect to three essential receptors such as the ecdysone receptor (EcR), urease, and HIV-integrase. Starting from a crystallographic structural study of accidentally harvested crystals of this compound, we performed docking studies to evaluate the inhibitory capacity of DBH toward three selected targets. A crystal morphology prediction was then performed.

Ligand Growing Experiments Suggested 4-amino and 4-ureido pyridazin-3(2)-one as Novel Scaffold for FABP4 Inhibition.

Fatty acid binding protein (FABP4) inhibitors are of synthetic and therapeutic interest and ongoing clinical studies indicate that they may be a promise for the treatment of cancer, as well as other diseases. As part of a broader research effort to develop more effective FABP4 inhibitors, we sought to identify new structures through a two-step computing assisted molecular design based on the established scaffold of a co-crystallized ligand. Novel and potent FABP4 inhibitors have been developed using this approach and herein we report the synthesis, biological evaluation and molecular docking of the 4-amino and 4-ureido pyridazinone-based series.

Targeting the SARS-CoV-2 HR1 with Small Molecules as Inhibitors of the Fusion Process.

The rapid and global propagation of the novel human coronavirus that causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of this virus. In this paper, we studied the spike protein S2 domain of SARS-CoV-2 as it is the most conserved component and controls the crucial fusion process of SARS-CoV-2 as a target for different databases of small organic compounds. Our in silico methodology, based on pharmacophore modeling, docking simulation and molecular dynamics simulations, was first validated with ADS-J1, a potent small-molecule HIV fusion inhibitor that has already proved effective in binding the HR1 domain and inhibiting the fusion core of SARS-CoV-1.

Adipocyte fatty acid binding protein 4 (FABP4) inhibitors. An update from 2017 to early 2022.

The fatty acid binding protein 4 (FABP4) is a protein predominantly expressed in macrophages and adipose tissue, where it regulates fatty acids storage and lipolysis and is an essential mediator of inflammation. Small molecule inhibitors of FABP4 have attracted interest following the recent publications of beneficial pharmacological effects of these compounds for the treatment of metabolic syndrome and, more recently, for other pathologies. Since the synthesis of the BMS309403, one of the first selective and effective FABP4 inhibitors, hundreds of other inhibitors have been synthesized (i.

Artificial Intelligence Technologies for COVID-19 De Novo Drug Design.

The recent covid crisis has provided important lessons for academia and industry regarding digital reorganization. Among the fascinating lessons from these times is the huge potential of data analytics and artificial intelligence. The crisis exponentially accelerated the adoption of analytics and artificial intelligence, and this momentum is predicted to continue into the 2020s and beyond.

Hydroxamic Acid-Based Histone Deacetylase (HDAC) Inhibitors Bearing a Pyrazole Scaffold and a Cinnamoyl Linker.

Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, recent studies have demonstrated that epigenetic mechanisms are also implicated in the insurgence and development of cancer. Patterns of the epigenetic component include DNA methylation and histone modifications.

FABP4 inhibitors 3D-QSAR model and isosteric replacement of BMS309403 datasets.

The data have been obtained from FABP4 inhibitor molecules previously published. The 120 compounds were used to build a 3D-QSAR model. The development of the QSAR model has been undertaken with the use of Forge software using the PM3 optimized structure and the experimental IC of each compound.