Medicinal chemistry silicon

Therapeutic drug monitoring (TDM) is an important tool in precision medicine as it allows estimating pharmacodynamic and pharmacokinetic effects of drugs in clinical settings. An accurate, fast and real-time determination of the drug concentrations in patients ensures fast decision-making processes at the bedside to optimize the clinical treatment. Surface-enhanced Raman spectroscopy (SERS), which is based on the application of metallic nanostructured substrates to amplify the inherent weak Raman signal, is a promising technique in medical research due to its molecular specificity and trace sensitivity accompanied with short detection times...

A high-throughput, rapid, and highly sensitive surface-enhanced Raman spectroscopy (SERS) microarray for screening multiple mycotoxins has been developed on a three-dimensional silver nanoparticle porous silicon (3D AgNP-Psi) SERS substrate, which was easy to be engineered by electrochemical etching and magnetron sputtering technology. The etching current density, etching waveform, and target material for magnetron sputtering have been investigated to obtain an optimal 3D SERS substrate. The optimized 3D AgNP-Psi SERS substrate showed an enhancement factor of 2...

BACKGROUND: Peptide nucleic acid (PNA) plays an important role in antimicrobial activity, but its cellular permeability is poor. To overcome this limitation, we constructed biomimetic nanoparticles by using extracellular vesicle (EV)-coated mesoporous silicon nanoparticles (MSNs) to deliver PNA to Staphylococcus aureus (S. aureus) and improve its antisense therapeutic effect. METHOD: MSN was prepared by the sol-gel method, and EV was extracted by affinity resin chromatography...

A new bioconjugation reagent containing silicon has been developed for the selective reaction with thiols. The inclusion of silicon significantly improves chemoselectivity and suppresses retro processes, thereby exceeding the capabilities of traditional reagents. The method is versatile and compatible with a broad range of thiols and unsaturated carbonyl compounds and yields moderate to high results. These reactions can be conducted under biocompatible conditions, thereby making them suitable for protein bioconjugation...

The invention of silica-based bioactive glass in the late 1960s has sparked significant interest in exploring a wide range of silicon-containing biomaterials from the macroscale to the nanoscale. Over the past few decades, these biomaterials have been extensively explored for their potential in diverse biomedical applications, considering their remarkable bioactivity, excellent biocompatibility, facile surface functionalization, controllable synthesis, etc. However, to expedite the clinical translation and the unexpected utilization of silicon-composed nanomedicine and biomaterials, it is highly desirable to achieve a thorough comprehension of their characteristics and biological effects from an overall perspective...

Synthesis and biological evaluation of silicon-incorporated phytocannabinoids with improved pharmacological properties toward inflammatory diseases are described. The synthesized sila-analogues 15a , 15b , and 15c displayed potent inhibition of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6 at 10 μM. Further, the release of heme during the lysis of red blood cells in hemolytic diseases is one of the major reasons for inflammation associated with the pathophysiology of these diseases...

A pharmacophore-hybridized strategy based on previously reported HSP90 C-terminal inhibitors was utilized to prepare 32 aryl/penta-1,4-dien-3-one/amine hybrids. Among them, a silicon-containing compound 1z exhibited remarkable broad-spectrum antiproliferative effects on various human breast cancer cell lines. Through fluorescence polarization and AlphaScreen-based assays, we demonstrated that 1z specifically inhibited the HSP90 C-terminus without affecting HSP90 N-terminus. Furthermore, 1z effectively inhibited the HSP90 C-terminus without inducing heat-shock response (HSR), leading to the degradation of its client proteins HER2, pAKT, AKT, and CDK4, causing G1 arrest of MCF-7 and SKBr3 cells, and ultimately contributing to apoptosis of these cells through caspase-3, caspase-8, and caspase-9 activation...

Semi-solid extrusion (SSE) 3D printing has recently attracted increased attention for its pharmaceutical application as a potential method for small-batch manufacturing of personalised solid dosage forms. It has the advantage of allowing ambient temperature printing, which is especially beneficial for the 3D printing of thermosensitive drugs. In this study, the effects of polymeric compositions (single hydroxypropyl methylcellulose (HPMC) system and binary HPMC + polyvinylpyrrolidone (PVP) system), disintegrant (silicon oxide (SiO2 )), and active pharmaceutical ingredients (tranexamic acid (TXA) and paracetamol (PAC)) on the printability of semisolid inks and the qualities of SSE printed drug-loaded tablets were investigated...

Lipophilicity is a physicochemical property with wide relevance in drug design, computational biology, and food, environmental and medicinal chemistry. Lipophilicity is commonly expressed as the partition coefficient for neutral molecules, whereas for molecules with ionizable groups, the distribution coefficient (D) at a given pH is used. The logDpH is usually predicted using a pH correction, while often ignoring the apparent ionic partition [[EQUATION]]. In this work, we studied the impact of [[EQUATION]] on the prediction of both the experimental lipophilicity of small molecules and experimental lipophilicity-based applications and metrics such as lipophilic efficiency (LipE), distribution of spiked drugs in milk products, and pH-dependent partition of water contaminants in synthetic passive samples such as silicones...

Incorporation of silicate ions in calcium phosphate ceramics (CPC) and modification of their multiscale architecture are two strategies for improving the vascularization of scaffolds for bone regenerative medicine. The response of endothelial cells, actors for vascularization, to the chemical and physical cues of biomaterial surfaces is little documented, although essential. We aimed to characterize in vitro the response of an endothelial cell line, C166, cultivated on the surface CPCs varying either in terms of their chemistry (pure versus silicon-doped HA) or their microstructure (dense versus microporous)...

Site-specific modification of thiol-containing biomolecules has been recognized as a versatile and powerful strategy for probing our biological systems and discovering novel therapeutics. The addition of lipophilic silicon moiety opens up new avenues for multi-disciplinary research with broad applications in both the medicinal and material sciences. However, adhering to the strict biocompatibility requirements, and achieving the introduction of labile silicon handle and high chemo-selectivity have been formidable...

Microfluidics has emerged as a powerful technology with diverse applications in microbiology, medicine, chemistry, and physics. While its potential for controlling and studying chemical reactions is well recognized, the extraction and analysis of useful chemical information generated within microfluidic devices remain challenging. This is mainly due to the limited tools available for in situ measurements of chemical reactions. In this study, we present a proof-of-concept spectIR-fluidic reactor design that combines microfluidics with Fourier transform infrared (FTIR) spectroscopy for in situ kinetic studies of fast reactions...

Growing global demand for new molecules to treat tuberculosis has created an urgent need to develop novel strategies to combat the menace. BM212 related compounds were found to be potent anti-TB agents and they inhibit mycolic acid transporter, MmpL3, a known potent drug target from Mycobacterium tuberculosis. In order to enhance their inhibitory potency, several silicon analogues of diarylpyrroles related to BM212 were designed, synthesized, and evaluated for anti-tubercular activities. In Alamar blue assay, most of the silicon-incorporated compounds were found to be more potent than the parent compound (BM212), against Mycobacterium tuberculosis (MIC = 1...

The miniaturization of traditional silicon-based electronics will soon reach its limitation as quantum tunneling and heat become serious problems at the several-nanometer scale. Crafting integrated circuits via self-assembly of electronically active molecules using a "bottom-up" paradigm provides a potential solution to these technological challenges. In particular, integrated biomolecular circuits (IbC) offer promising advantages to achieve this goal, as nature offers countless examples of functionalities entailed by self-assembly and examples of controlling charge transport at the molecular level within the self-assembled structures...

Magnetic bioactive glass-ceramic (MGC) powders with nominal compositions of (45 - x )SiO2 24.5CaO24.5Na2 O6P2 O5 x Fe2 O3 ( x = 2, 4, 6, 8, 10, and 15 wt%) have been synthesized by a sol-gel route by systematically substituting silicon dioxide with iron oxide in Hench's 45S5 glass composition. Powder X-ray diffraction studies revealed a variation in the percentage of combeite (Ca2 Na2 Si3 O9 ), magnetite (Fe3 O4 ), and hematite (Fe2 O3 ) nanocrystalline phases in MGC powders as a function of composition. Zeta potential measurements showed that MGC containing up to 10 wt% iron oxide formed stable suspensions...

Fibroblasts geometrically confined by photo-immobilized gelatin micropatterns were subjected to cyclic stretch on the silicone elastomer. By using covalently micropatterned surfaces, the cell morphologies such as cell area and length were quantitatively investigated under a cyclic stretch for 20 hours. The mechanical forces did not affect the cell growth but significantly altered the cellular morphology on both non-patterned and micropatterned surfaces. It was found that cells on non-patterns showed increasing cell length and decreasing cell area under the stretch...

Hydrogels with adaptable optical and mechanical characteristics show considerable promise for light delivery in vivo with neuroengineering applications. However, the unlinked amorphous polymer chains within hydrogels can cause volumetric swelling after water absorption under physiological conditions over time. Chemically cross-linked poly(vinyl alcohol) (PVA) hydrogels showcase fatigue-resistant attributes and promising biocompatibility for the manufacture of soft neural probes. However, possible swelling of the PVA hydrogel matrix could impact the structural stability of hydrogel-based bioelectronics and their long-term in vivo functionality...

Absorbable polymers have attracted increasing attention in the field of bone regeneration in recent years for their degradation. Compared with other degradable polymers, polypropylene carbonate (PPC) has several advantages such as biodegradation and relatively cheap raw materials. Most importantly, PPC can degrade into water and carbon dioxide totally which does not give rise to local inflammation and bone resorption in vivo . However, pure PPC has not presented excellent osteoinductivity properties. In order to enhance the osteoinductivity of PPC, silicon nitride (SiN) was employed due to its excellent mechanical properties, biocompatibility and osteogenesis compared with the other common materials such as hydroxyapatite and calcium phosphate ceramics...

With the rapid development of science and technology, superhydrophobic nanomaterials have become one of the hot topics from various subjects. Due to their distinct properties, such as superhydrophobicity, anti-icing and corrosion resistance, superhydrophobic nanomaterials are widely used in industry, agriculture, defense, medicine and other fields. Hence, the development of superhydrophobic materials with superior performance, economical, practical features, and environment-friendly properties are extremely important for industrial development and environmental protection...

Skin repair encompasses epidermal barrier repair and wound healing which involves multiple cellular and molecular stages. Therefore, many skin repair strategies have been proposed. In order to characterize the usage frequency of skin repair ingredients in cosmetics, medicines, and medical devices, commercialized in Portuguese pharmacies and parapharmacies, a comprehensive analysis of the products' composition was performed. A total of 120 cosmetic products, collected from national pharmacies online platforms, 21 topical medicines, and 46 medical devices, collected from INFARMED database, were included in the study, revealing the top 10 most used skin repair ingredients in these categories...