Medicinal chemistry silicon

Partial or whole regeneration of the uterine endometrium using extracellular matrix (ECM)-based scaffolds is a therapeutic strategy for uterine infertility due to functional and/or structural endometrial defects. Here, we examined whether the entire endometrium can be regenerated circumferentially using an acellular ECM scaffold (decellularized endometrial scaffold, DES) prepared from rat endometrium. We placed a silicone tube alone to prevent adhesions or a DES loaded with a silicone tube into a recipient uterus in which the endometrium had been surgically removed circumferentially...

Bioisosterism is one of the leading strategies in medicinal chemistry for the design and modification of drugs, consisting in replacing an atom or a substituent with a different atom or a group with similar chemical properties and an inherent biocompatibility. The objective of such an exercise is to produce a diversity of molecules with similar behavior while enhancing the desire biological and pharmacological properties, without inducing significant changes to the chemical framework. In drug discovery and development, the optimization of the absorption, distribution, metabolism, elimination, and toxicity (ADMETox) profile is of paramount importance...

Polymer coatings containing both fouling-resistant and fouling-release components have been reported to show synergistic antifouling properties. However, it remains unclear how the polymer composition influences the antifouling performance, particularly regarding foulants of different sizes and biological natures. Herein, we prepare dual functionalized brush copolymers containing fouling-resistant poly(ethylene glycol) (PEG) and fouling-release polydimethylsiloxane (PDMS) and examine their antifouling performances against different biofoulants...

Alzheimer's disease (AD) is a major group of diseases that threaten human health, and the search for drugs and treatments for it has never stopped. Research and development of NMDA receptor antagonists as potential therapeutic targets have also been ongoing. Our group designed and synthesized 22 new tetrahydropyrrolo[2,1-b]quinazolines based on NR2B-NMDARs targets and evaluated them for their neuroprotective activity against NMDA-induced cytotoxicity in vitro, A21 exhibited excellent neuroprotective activity...

Constructing an antifouling surface cost-effectively is vitally important for many applications. Herein, a series of silicon substrates with micro-pyramid structures and p-n junctions were fabricated following a simple industrial processing flow, among which the p+ n-Si substrate, fabricated through boron doping of a micro-pyramid structured n-type silicon wafer, exhibited the most pronounced antibacterial performance. Broad-spectrum bactericidal and bacteriostatic activity of p+ n-Si under ambient light illumination was observed, with an inhibition ability of 73-100% compared to that of a bare glass against both airborne and contact-transmitted bacteria in the intensive care unit...

Silanols are valuable and important compounds, which have found widespread applications in the field of materials science, synthetic chemistry, and medicinal chemistry. Although a handful of approaches have been developed for the synthesis of various silanols, access to enantioenriched silicon-stereogenic silanols remains underdeveloped. This concept intends to summarize and highlight recent advances in the construction of silicon-stereogenic silanols and endeavors to encourage further research in this area...

Regeneration of dental pulp via the transplantation of dental pulp stem cells (DPSCs) has emerged as a novel therapy for dental pulp necrosis after inflammation and injury. However, providing sufficient oxygen and nutrients to support stem cell survival, self-renewal, and differentiation in the narrow root canal remains a great challenge. In this study, we explored a novel strategy based on cell-laden microfibers for dental pulp regeneration. Firstly, we fabricated suitable GelMA hydrogels that facilitate the survival and proliferation of DPSCs and human umbilical vein endothelial cells (HUVECs) and possess satisfactory biomechanical properties to generate microfibers...

The major challenges in photodynamic therapy (PDT) are the neutralization of cytotoxic reactive oxygen species (ROS) by the excessive antioxidant glutathione (GSH) in tumor cells, high self-aggregation of most photosensitizers (PSs), and long time to protect from light after treatment. Thus, to develop the molecular PSs for the improved and safe PDT in clinic, a novel and versatile PS (Mal-Pc) has been designed by di-substituting maleimides to the axial positions of silicon (Ⅳ) phthalocyanine. Owning to the conjugation of maleimides, Mal-Pc can not only entry tumor cells more easily and faster, but also can react with the intracellular overexpressed GSH after entry...

Compared to the activation of acquired immunity by the immune checkpoint blockade, the activation of innate immunity via anti-phagocytosis checkpoint blockade could significantly increase the beneficiary population of immunotherapy. However, the activation of innate immunity and the occurrence of phagocytosis are only accomplished when the interaction between pro-phagocytosis signals and anti-phagocytosis signals is realized. Herein, a versatile nanoplatform (DHMR) based on mesoporous silicon nanoparticles (MSNPs) has been constructed...

Biofilm formation on biomedical devices is a major cause of device-associated infection. Traditional antibiotic treatment for biofilm-associated infection increases the risk of multidrug resistance. Thus, there is an urgent need to develop antibiotic-free strategies to prevent biofilm formation on biomedical devices. Herein, we report a layer-by-layer strategy to construct an antifouling and bactericidal dual-functional coating for silicone rubber (SR)-based substrates. Five zwitterionic active ester copolymers, p(SBMA- co -NHSMA), with varied zwitterionic pSBMA components that ranged from 50 to 90% (molar ratio) were precisely prepared...

The cyclic structure of proline (Pro) confers unique conformational properties on this natural amino acid that influences polypeptide structure and function. Pseudoprolines are a family of Pro isosteres that incorporate a heteroatom, most prominently oxygen or sulfur but also silicon and selenium, to replace the Cβ or Cγ carbon atom of the pyrrolidine ring. These readily synthetically accessible structural motifs can facilitate facile molecular editing in a fashion that allows modulation of the amide bond topology of dipeptide elements and influence over ring pucker...

Silicon quantum dots (SiQDs) have fully demonstrated their applicability in light of their fluorescence. The extension of their applications to other fields, especially considering their excellent biocompatibility, would be more appealing. Herein, a kind of versatile nitrogen-doped silicon quantum dot (N-SiQD) was facilely synthesized via a one-pot hydrothermal method with 3-aminopropyltrimethoxysilane and tetraethylpentylamine as sources. The N-SiQDs were used as a probe for bacterial imaging owing to their good fluorescence properties, stability and biocompatibility...

Glucose biosensors that could be subcutaneously injected and interrogated without a physically connected electrode and transmitter affixed to skin would represent a major advancement in reducing the user burden of continuous glucose monitors (CGMs). Towards this goal, an optical glucose biosensor was formed by strategically tailoring a thermoresponsive double network (DN) membrane to house a phosphorescence lifetime-based glucose sensing assay. This membrane was selected based on its potential to exhibit reduced biofouling via 'self-cleaning' due to cyclical deswelling/reswelling in vivo ...

Antibiotics are a category of chemical compounds used to treat bacterial infections and are widely applied in cultivation, animal husbandry, aquaculture, and pharmacy. Currently, residual antibiotics and their metabolites pose a potential risk of allergic reactions, bacterial resistance, and increased cancer incidence. Residual antibiotics and the resulting bacterial antibiotic resistance have been recognized as a global challenge that has attracted increasing attention. Therefore, monitoring antibiotics is a critical way to limit the ecological risks from antibiotic pollution...

The development of a fast and safe reactive oxygen species (ROS)-responsive vector is generally limited by the intracellular unstable ROS concentration, and a relatively long time is still needed for the complete intracellular release of drugs or genes induced by ROS. In this work, a gene transfection platform based on ROS-responsive silicon nanowire arrays (SN) is developed, to promote the gene transfection efficiency for several cell lines. Briefly, the surface of the ROS generating system, gold nanoparticle modified SN (SN-Au), is grafted with poly[(2-acryloyl)ethyl( p -boronic acid benzyl)diethylammonium bromide] (B-PDEAEA), an oxidation-responsive charge-reversal cationic polymer...

A scaffold is one of the most significant implants for treating bone injury, while the precise control of stem cell proliferation and differentiation within a scaffold is still challenging. In this work, a composite scaffold was designed to be capable of recruiting endogenous stem cells, stimulating osteogenic differentiation and achieving significant bone repair function. The designed SiCP + SF@PFS silica-calcium phosphate composite scaffold was obtained by mixing the peptide PFS containing silk fibroin solution with the SiCP scaffold, and treating with horseradish peroxidase and H2 O2 ...

Pretargeted PET imaging allows the use of radiotracers labeled with short-living PET radionuclides for tracing drugs with slow pharmacokinetics. Recently, especially methods based on bioorthogonal chemistry have been under intensive investigation for pretargeted PET imaging. The pharmacokinetics of the radiotracer is one of the factors that determine the success of the pretargeted strategy. Here, we report synthesis and biological evaluation of two 68 Ga-labeled tetrazine (Tz)-based radiotracers, [68 Ga]Ga-HBED-CC-PEG4 -Tz ([68 Ga]4) and [68 Ga]Ga-DOTA-PEG4 -Tz ([68 Ga]6), aiming for development of new tracer candidates for pretargeted PET imaging based on the inverse electron demand Diels-Alder (IEDDA) ligation between a tetrazine and a strained alkene, such as trans-cyclooctene (TCO)...

Recently inorganic-based metallodrugs provide an effective mechanism for the drugs on the choice of metal and its properties. Medicinal complex compounds provide an efficient platform for various pharmacological and therapeutic applications. Six new organotin and organosilicon complexes containing sulphur and nitrogen donor atoms were synthesised. These complexes of ( E )-2-((4-methoxybenzylidene)amino)benzenethiol were characterized by elemental analyses, molecular weights, conductance measurements, infrared, electronic, and NMR spectroscopy...

One of the most straightforward approaches to access chiral silanes is catalytic enantioselective hydrosilylation. Although significant advances have been achieved in enantioselective construction of either a carbon-stereogenic center or a silicon-stereogenic center through enantioselective hydrosilylation, simultaneous establishment of a carbon- and a silicon-stereogenic center in an acyclic molecule through a single intermolecular hydrosilylation remained undeveloped. Herein, an unprecedented cobalt-catalyzed regio-, diastereo- and enantioselective hydrosilylation of 1,3-dienes is presented, enabling construction of a carbon- and a silicon-stereogenic center in a single intermolecular transformation...

Liver X receptor (LXR) α and LXRβ are nuclear receptors playing key roles in lipid metabolism, and LXR ligands are attractive drug candidates for metabolic disorders. Here we report the structural development of 4-(1,1,1,3,3,3-hexafluoro-2-hydroxyprop-2-yl)phenylsilane derivatives as LXR agonists bearing silyl functionalities as the hydrophobic pharmacophore, based on the structure of the known sulfonamide LXR agonist T0901317. Most of the synthesized compounds exhibit agonistic activity toward LXRs, but the LXR subtype-selectivity differs depending upon the substituents on the silicon atom...