Lead Structure Research Articles

Utilizing Metasurfaces for Directional Control of LED Emission

This study provides a detailed modeling and analysis of four different three-dimensional GaN-based LED structures. The results reveal that incorporating DBRs effectively focuses light and enhances the light extraction efficiency (LEE). Additionally, the integration of Metasurface in the Micro-LED+DBRs+M structure allows for precise control of light emission direction and further radiation focusing. Furthermore, in the Micro-LED+DBRs+M2 structure with improved periodic nanocolumns, the light beam can be deflected simultaneously in multiple directions. These findings offer new possibilities for the advancement of LED technology.

Discovery of Piperazin‐2‐yl‐pyrimidines as Anticancer Agents via Targeting JNK Signaling Pathway in Human MCF‐7 Breast Carcinoma

AbstractBreast cancer (BC) is the second leading cause of cancer‐related mortality in women, and targeting biological pathways such as the JNK pathway has proven to be a viable therapeutic target for BC therapy. Here, we synthesized piperazin‐2‐yl‐pyrimidines and evaluated them for anticancer activity against MCF‐7 cells. In addition, antioxidant, reactive oxygen species (ROS) inhibition, caspase activity, and toxicity in platelets were studied in the presence and absence of active compound IA‐6 or IA‐7. Our detailed experimental analysis found that the compound IA‐7 showed anticancer activity by either activating p‐JNK or by inducing radical species in cancer and thrombosis model. Evident to in vitro analysis, the structure based molecular interaction studies of binding of IA‐7 to JNK3S exhibited a significant binding energy of −7.56 kcal/mol which was found to be a better binder when compared to previously reported JNK inducer (PC‐12). Overall, we herein report the analytically pure IA‐7 as lead structure that could be used as a template to develop target based anticancer agents where JNK modulation is predominant.

Host-Guest Interactions of Ruthenium(II) Arene Complexes with Cucurbit[7/8]uril.

Cucurbit[n]urils (CB[n]s) have been recognized for their chemical and thermal stability, and their ability to bind many neutral and cationic guest molecules makes them excellent hosts in a range of supramolecular applications. In drug delivery, CB[n]s can enhance drug solubility, improve chemical and physical drug stability, and allow for triggered and controlled release. This study aimed to investigate the ability of CB[7] and CB[8] as molecular hosts to bind ruthenium(II) arene complexes that are current anticancer lead structures in the area of metallodrugs. Both, experimental and computational methods, led to insights into the binding preferences and geometries of [RuII(cym)Cl2]2 (1; cym = η6-p-cymene), [RuII(cym)(dmb)Cl2]) (2; cym = η6-p-cymene; dmb = 1,3-dimethylbenzimidazol-2-ylidene), and [RuII(cym)(pta)Cl2] (3, RAPTA-C; cym = η6-p-cymene; pta = 1,3,5-triaza-7-phospha-adamantane) with CB[7] and CB[8]. Competition experiments by mass spectrometry revealed clear preferences of 2 for CB[8] and 3 for CB[7]. Based on a comparison of the associated interaction energies from quantum chemical calculations as well as experimental data, 3@CB[7] clearly prefers a binding mode, where the pta ligand is located inside the cavity of the host, and the metal ion interacts with two of the carbonyl groups on the rim of CB[7]. In contrast, complex 2 binds in two different orientations with interaction energies similar to those of both CB[n]s, with the cym ligand being either inside or outside of the cavity. These findings suggest that ruthenium(II) arene complexes are able to form stable host-guest interactions with CB[n]s, which can be exploited as drug delivery vehicles in further metallodrug development to improve their chemical stability.

Design and Synthesis of Gefitinib Derivatives as Potential Drugs fo r Cancer Treatment: Antiproliferative Activity, Molecular Docking, and ADMET Prediction

Background: Non-small cell lung cancer is one of the most common cancers worldwide, and targeted chemotherapy has become a kind of the main treatment. Gefitinib, the most widely studied targeted agent in non-small cell lung cancer, is an orally active tyrosine kinase inhibitor. However, gefitinib inevitably generates acquired drug resistance, leading to treatment failure. Objective: A new class of compounds containing 4-anilinoquinazoline lead structure was designed and synthesized by modifying the structure of gefitinib. These compounds are expected to exert better anticancer activity and better binding to the EGFR-TK domain, enrich the structure of 4-anilinoquinazoline derivatives and inspire further structural modifications. Methods: The antiproliferative activity of nine derivatives was determined in three cancer cell lines (A549, PC9, and HepG2) using the MTT method. The ADMET profile of all compounds was predicted, and the binding affinity of the compounds (5 and 6) to EGFR was predicted by Schrödinger. In addition, the effect of these compounds (3-6) in inducing apoptosis in HepG2 cells was also studied. Results: Four (3, 5, 6 and 9) of the newly synthesized derivatives exhibited superior antiproliferative activity against A549 to gefitinib (IC50 = 12.64 ± 3.59 μM), with compound 5 having the best activity (IC50 = 7.39 ± 1.24 μM). Moreover, the ability of compounds (3-6) to induce HepG2 cell apoptosis was significantly better than that of gefitinib. Conclusion: Nine structures (compounds 2-10) were synthesized and characterized, and compound 5 had the best antiproliferative activity. Compound 3 possessed the best ability to induce HepG2 apoptosis. Also, ADMET calculations were performed in silico, and the results revealed that compound 3 has more suitable characteristics as a potential drug candidate.

New 3-(Dibenzyloxyphosphoryl)isoxazolidine Conjugates of N1-Benzylated Quinazoline-2,4-diones as Potential Cytotoxic Agents against Cancer Cell Lines.

In this study, a new series of cis and trans 5-substituted-3-(dibenzyloxyphosphoryl)isoxazolidines 16a-g were synthesized by the 1,3-dipolar cycloaddition reaction of N-benzyl-C-(dibenzyloxyphosphoryl)nitrone and selected N1-allyl-N3-benzylquinazoline-2,4-diones. All the obtained trans-isoxazolidines 16a-g and the samples enriched in respective cis-isomers were evaluated for anticancer activity against three tumor cell lines. All the tested compounds exhibited high activity against the prostate cancer cell line (PC-3). Isoxazolidines trans-16a and trans-16b and diastereoisomeric mixtures of isoxazolidines enriched in cis-isomer using HPLC, namely cis-16a/trans-16a (97:3) and cis-16b/trans-16b (90:10), showed the highest antiproliferative properties towards the PC-3 cell line (IC50 = 9.84 ± 3.69-12.67 ± 3.45 μM). For the most active compounds, induction apoptosis tests and an evaluation of toxicity were conducted. Isoxazolidine trans-16b showed the highest induction of apoptosis. Moreover, the most active compounds turned out safe in vitro as none affected the cell viability in the HEK293, HepG2, and HSF cellular models at all the tested concentrations. The results indicated isoxazolidine trans-16b as a promising new lead structure in the search for effective anticancer drugs.

Comparative study on the effect of SRB and Sporosarcina pasteurii on the MICP cementation and solidification of lead–zinc tailings

The production of tailings sand due to mining and smelting activities is one of the reasons for the accelerated environmental pollution caused by heavy metals, drawing social attention to the management of tailings sand. Microbially induced carbonate precipitation (MICP) is an environmentally friendly soil remediation technique that is gradually becoming the preferred method for soil stabilisation and heavy metal pollution control. To address the issues of heavy metal pollution release and the loose particle structure of lead–zinc tailings sand (LZTS), this study employs a layered MICP approach. The solidification effects of two typical mineralising bacteria, sulfate-reducing bacteria (SRB) and Sporosarcina pasteurii, on LZTS, were compared for the first time. The results show that the maximum unconfined compressive strength (UCS) of SRB cemented solidified lead–zinc tailings sand (SRB-CS-LZTS) specimens is 0.22 MPa, while that of S. pasteurii cemented solidified lead–zinc tailings sand (SP-CS-LZTS) specimens is 0.95 MPa. Compared with the UCS of SRB-CS-LZTS, the UCS of SP-CS-LZTS increased by 3.32 times. The effect of S. pasteurii on the improvement of UCS and immobilisation of heavy metal ions was greater than that of SRB. The immobilisation effect of SRB on SO42- in the LZTS was better than that of S. pasteurii. Compared with SRB, the biological CaCO3 formed by S. pasteurii exhibited stronger adhesion and was more suitable for the cementation and solidification of LZTS. This study uses MICP technology to treat LZTS, aligning with the green environmental concept and providing a reference for the bioremediation of multiple heavy metals in tailing areas.

Structure-Based Design and Synthesis of Covalent Inhibitors for Deubiquitinase and Acetyltransferase ChlaDUB1 of Chlamydia trachomatis.

Upon infection by an intracellular pathogen, host cells activate apoptotic pathways to limit pathogen replication. Consequently, efficient proliferation of the obligate intracellular pathogen Chlamydia trachomatis, a major cause of trachoma and sexually transmitted diseases, depends on the suppression of host cell apoptosis. C. trachomatis secretes deubiquitinase ChlaDUB1 into the host cell, leading among other interactions to the stabilization of antiapoptotic proteins and, thus, suppression of host cell apoptosis. Targeting the bacterial effector protein may, therefore, lead to new therapeutic possibilities. To explore the active site of ChlaDUB1, an iterative cycle of computational docking, synthesis, and enzymatic screening was applied with the aim of lead structure development. Hereby, covalent inhibitors were developed, which show enhanced inhibition with a 22-fold increase in IC50 values compared to previous work. Comprehensive insights into the binding prerequisites to ChlaDUB1 are provided, establishing the foundation for an additional specific antichlamydial therapy by small molecules.

Tetrazole-Functionalized Organoboranes Exhibiting Dynamic Intramolecular N→B-Coordination and Cyanide-Selective Anion Binding.

Starting from two different cyano-functionalized organoboranes, we demonstrate that 1,3-dipolar [3+2] azide-nitrile cycloaddition can serve to generate libraries of alkyl-tetrazole-functionalized compounds capable of intramolecular N→B-Lewis adduct formation. Due to the relatively low basicity of tetrazoles, structures can be generated that exhibit weak and labile N→B-coordination. The reaction furnishes 1- and 2-alkylated regio-isomers that exhibit different effective Lewis-acidities at the boron centers, and vary in their optical absorption and fluorescence properties. Indeed, we identified derivatives capable of selectively binding cyanide over fluoride, as confirmed by 11B NMR. This finding demonstrates the potentialities of this synthetic strategy to systematically fine-tune the properties of lead structures that are of interest as chemical sensors.

Synthesis of ionizable lipopolymers using split-Ugi reaction for pulmonary delivery of various size RNAs and gene editing.

We present an efficient approach for synthesizing cationic poly(ethylene imine) derivatives using the multicomponent split-Ugi reaction to rapidly create a library of complex functional ionizable lipopolymers. We synthesized a diverse library of 155 polymers, formulated them into polyplexes to establish structure-activity relationships crucial for endosomal escape and efficient transfection. After discovering a lead structure, lipopolymer-lipid hybrid nanoparticles are introduced to preferentially deliver to and elicit effective mRNA transfection in lung endothelium and immune cells, including T cells with low in vivo toxicity. The lipopolymer-lipid hybrid nanoparticles showed 300-fold improvement in systemic mRNA delivery to the lung compared to in vivo -JetPEI ® . Lipopolymer-lipid hybrid nanoparticles demonstrated efficient delivery of mRNA-based therapeutics for treatment of two different disease models. Lewis Lung cancer progression was significantly delayed after treatment with loaded IL-12 mRNA in U155@lipids after repeated i.v. administration. Systemic delivery of human CFTR (hCFTR) mRNA resulted in production of functional form of CFTR protein in the lungs. The functionality of hCFTR protein was confirmed by restoration of CFTR- mediated chloride secretion in conductive airway epithelia in CFTR knockout mice after nasal instillation of hCFTR mRNA loaded U155@lipids. We further showed that, U155@lipids nanoparticles can deliver complex CRISPR-Cas9 based RNA cargo to the lung, achieving 5.6 ± 2.4 % gene editing in lung tissue. Moreover, we demonstrated successful PD-1 gene knockout of T cells in vivo . Our results highlight a versatile delivery platform for systemic delivering of mRNA of various sizes for gene therapy for a variety of therapeutics.

High Efficiency Flat-Type GaN-Based Light-Emitting Diodes with Multiple Local Breakdown Conductive Channels.

We investigated a flat-type p*-p LED composed of a p*-electrode with a local breakdown conductive channel (LBCC) formed in the p-type electrode region by applying reverse bias. By locally connecting the p*-electrode to the n-type layer via an LBCC, a flat-type LED structure is applied that can replace the n-type electrode without a mesa-etching process. Flat-type p*-p LEDs, devoid of the mesa process, demonstrate outstanding characteristics, boasting comparable light output power to conventional mesa-type n-p LEDs at the same injection current. However, they incur higher operating voltages, attributed to the smaller size of the p* region used as the n-type electrode compared to conventional n-p LEDs. Therefore, despite having comparable external quantum efficiency stemming from similar light output, flat-type p*-p LEDs exhibit diminished wall-plug efficiency (WPE) and voltage efficiency (VE) owing to elevated operating voltages. To address this, our study aimed to mitigate the series resistance of flat-type p*-p LEDs by augmenting the number of LBCCs to enhance the contact area, thereby reducing overall resistance. This structure holds promise for elevating WPE and VE by aligning the operating voltage more closely with that of mesa-type n-p LEDs. Consequently, rectifying the issue of high operating voltages in planar p*-p LEDs enables the creation of efficient LEDs devoid of crystal defects resulting from mesa-etching processes.

Newly synthesized based Schiff of phenylferrocene: Molecular and crystal structures, Density Functional Theory calculations, Hirshfeld surface analyses, and improved molecular docking data

In three steps, ferrocene-derived Schiff bases were synthesized, beginning with an arylation reaction, followed by a reduction reaction. The last step describes a condensation reaction between 4-ferrocenylaniline 2a and various aromatic aldehydes in ethanol under reflux. Several techniques were used to determine the structures of the prepared compounds, including 1HNMR , 13CNMR , FTIR, UV/Vis and single crystal X-ray diffraction for compounds 3a, 3f, and 3j. Hirshfeld surface analysis measurements were also performed to measure the interaction energies between molecules. Moreover, the geometric structure of the selected compound (3a, 3f, and 3j) was optimized using a computational analysis involving density functional theory (DFT) calculations based on B3LYP/6–31 G (d, p). Strong binding affinities were observed via both hydrophobic and H-bond interactions with pertinent molecules when molecular docking investigations were conducted on the target crystal structure, the FabX (7e1q). The maximum binding energy is found in the 3d, at -7.99 kcal/mol. Therefore, it is feasible that this structure will work well as a potential lead structure for the synthesis and design of stronger inhibitors that can be used in conjunction with anti-corrosive drugs to treat gastric cancer.

Etching-free pixel definition in InGaN green micro-LEDs

The traditional plasma etching process for defining micro-LED pixels could lead to significant sidewall damage. Defects near sidewall regions act as non-radiative recombination centers and paths for current leakage, significantly deteriorating device performance. In this study, we demonstrated a novel selective thermal oxidation (STO) method that allowed pixel definition without undergoing plasma damage and subsequent dielectric passivation. Thermal annealing in ambient air oxidized and reshaped the LED structure, such as p-layers and InGaN/GaN multiple quantum wells. Simultaneously, the pixel areas beneath the pre-deposited SiO2 layer were selectively and effectively protected. It was demonstrated that prolonged thermal annealing time enhanced the insulating properties of the oxide, significantly reducing LED leakage current. Furthermore, applying a thicker SiO2 protective layer minimized device resistance and boosted device efficiency effectively. Utilizing the STO method, InGaN green micro-LED arrays with 50-, 30-, and 10-µm pixel sizes were manufactured and characterized. The results indicated that after 4 h of air annealing and with a 3.5-μm SiO2 protective layer, the 10-µm pixel array exhibited leakage currents density 1.2 × 10−6 A/cm2 at −10 V voltage and a peak on-wafer external quantum efficiency of ~6.48%. This work suggests that the STO method could become an effective approach for future micro-LED manufacturing to mitigate adverse LED efficiency size effects due to the plasma etching and improve device efficiency. Micro-LEDs fabricated through the STO method can be applied to micro-displays, visible light communication, and optical interconnect-based memories. Almost planar pixel geometry will provide more possibilities for the monolithic integration of driving circuits with micro-LEDs. Moreover, the STO method is not limited to micro-LED fabrication and can be extended to design other III-nitride devices, such as photodetectors, laser diodes, high-electron-mobility transistors, and Schottky barrier diodes.

Cocatalytic Activity of the Furfuryl and Oxanorbornane-Substituted Guanidines in the Aldol Reaction Catalyzed by (S)-Proline

This work investigated the cocatalytic activity of recently prepared guanidinium salts containing an oxanorbornane subunit in an (S)-proline-catalyzed aldol reaction. The activity was interpreted by the diastereoselectivity of the reaction (anti/syn ratio) and for the most interesting polycyclic guanidinium salt, the enantioselectivity of the reaction was determined. The results indicated a negative impact on the oxanorbornane unit if present as the flexible substituent. For most of the tested aldehydes, the best cocatalysts provided enantioselectivities above 90% and above 95% at room temperature and 0 °C, respectively, culminating in >99.5% for 4–chloro– and 2–nitrobenzaldehyde as the substrate. The barriers for forming four possible enantiomers were calculated and the results for two anti–enantiomers are qualitatively consistent with the experiment. Obtained results suggest that the representatives of furfurylguanidinium and rigid polycyclic oxanorbornane-substituted guanidinium salts are good lead structures for developing new cocatalysts by tuning the chemical space around the guanidine moiety.

Fungicidal Activity of New Pyrrolo[2,3-d]thiazoles and Their Potential Action on the Tryptophan Metabolic Pathway and Wax Biosynthesis.

The main challenge in the development of agrochemicals is the lack of new leads and/or targets. It is critical to discover new molecular targets and their corresponding ligands. YZK-C22, which contains a 1,2,3-thiadiazol-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole skeleton, is a fungicide lead compound with broad-spectrum fungicidal activity. Previous studies suggested that the [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole scaffold exhibited good antifungal activity. Inspired by this, a series of pyrrolo[2,3-d]thiazole derivatives were designed and synthesized through a bioisosteric strategy. Compounds C1, C9, and C20 were found to be more active against Rhizoctonia solani than the positive control YZK-C22. More than half of the target compounds provided favorable activity against Botrytis cinerea, where the EC50 values of compounds C4, C6, C8, C10, and C20 varied from 1.17 to 1.77 μg/mL. Surface plasmon resonance and molecular docking suggested that in vitro potent compounds C9 and C20 have a new mode of action instead of acting as pyruvate kinase inhibitors. Transcriptome analysis revealed that compound C20 can impact the tryptophan metabolic pathway, cutin, suberin, and wax biosynthesis of B. cinerea. Overall, pyrrolo[2,3-d]thiazole is discovered as a new fungicidal lead structure with a potential new mode of action for further exploration.

Isolation of anthraquinone derivatives from Rubia cordifolia (Rubiaceae) and their bioactivities against plant pathogenic microorganisms.

The discovery of antimicrobial ingredients from natural products could be an effective way to create novel fungicides. Rubia cordifolia L., a traditional Chinese herb, may have antimicrobial effects on plant pathogens according to our previous screening study. Rubia cordifolia L. extracts had moderate inhibitory effects on apple Valsa canker (Valsa mali) and tomato grey mould (Botrytis cinerea) at a concentration of 10 mg mL-1. With the use of bioguided isolation methods, eight compounds (1-8) were obtained, including the new compound 2,2,6-trimethyl-6-(4-methylphenyl)-tetrahydropyrano- 3-ol (7), and seven quinone derivatives. Two compounds, mollugin (1) and 1,3,6-trihydroxy-2-methylanthraquinone (6), were found to exhibit outstanding antifungal activities against V. mali and Phytophthora capsici Leon. The half maximal effective concentration (EC50) of compound 1 and compound 6 against V. mali were 79.08 and 81.78 μg mL-1, respectively, and the EC50 of compound 6 against P. capsici was 4.86 μg mL-1. Compound 1 also showed excellent activity against tobacco mosaic virus (TMV). The inactive, inductive, protective and curative activities against TMV were 84.29%, 83.38%, 86.81%, and 60.02%, respectively, at a concentration of 500 μg mL-1, which were all close to or greater than that of the positive control (100 μg mL-1 chitosan oligosaccharide, COS). Mollugin and 1,3,6-trihydroxy-2-methylanthraquinone are potentially valuable active compounds that lay a foundation for research on botanical fungicide products derived from R. cordifolia L. and provide lead structures for quinone derivative synthesis and structural modification. © 2024 Society of Chemical Industry.

11-Hydroxy-7-Methoxy-2,8-Dimethyltetracene-5,12-Dione

Microorganisms are a valuable source of pharmaceutically active chemicals, serving as scaffolds for synthesis as well as lead structures. Investigating novel biomes frequently yields intriguing chemistry; the Atacama Desert in Chile is one such example. This study reports the isolation of a new reduced anthracycline-related compound from the Atacama Desert-derived bacterium Saccharothrix S26. Structural characterisation was achieved by one-dimensional and two-dimensional NMR, HR-LCMS, and X-ray crystallography. The compound was tested against the ESKAPE pathogens, bovine mastitis-related pathogens, and the fungal strain Cryptococcus neoformans, but no antimicrobial activity was observed.

Tannic acid inhibits Escherichia coli biofilm formation and underlying molecular mechanisms: Biofilm regulator CsgD

Biofilms often engender persistent infections, heightened antibiotic resistance, and the recurrence of infections. Therefor, infections related to bacterial biofilms are often chronic and pose challenges in terms of treatment. The main transcription regulatory factor, CsgD, activates csgABC-encoded curli to participate in the composition of extracellular matrix, which is an important skeleton for biofilm development in enterobacteriaceae. In our previous study, a wide range of natural bioactive compounds that exhibit strong affinity to CsgD were screened and identified via molecular docking. Tannic acid (TA) was subsequently chosen, based on its potent biofilm inhibition effect as observed in crystal violet staining. Therefore, the aim of this study was to investigate the specific effects of TA on the biofilm formation of clinically isolated Escherichia coli (E. coli). Results demonstrated a significant inhibition of E. coli Ec032 biofilm formation by TA, while not substantially affecting the biofilm of the ΔcsgD strain. Moreover, deletion of the csgD gene led to a reduction in Ec032 biofilm formation, alongside diminished bacterial motility and curli synthesis inhibition. Transcriptomic analysis and RT-qPCR revealed that TA repressed genes associated with the csg operon and other biofilm-related genes. In conclusion, our results suggest that CsgD is one of the key targets for TA to inhibit E. coli biofilm formation. This work preliminarily elucidates the molecular mechanisms of TA inhibiting E. coli biofilm formation, which could provide a lead structure for the development of future antibiofilm drugs.

Biological and Medicinal Properties of Natural Chromones and Chromanones.

Emerging threats to human health require a concerted effort to search for new treatment therapies. One of the biggest challenges is finding medicines with few or no side effects. Natural products have historically contributed to major advances in the field of pharmacotherapy, as they offer special characteristics compared to conventional synthetic molecules. Interest in natural products is being revitalized, in a continuous search for lead structures that can be used as models for the development of new medicines by the pharmaceutical industry. Chromone and chromanones are recognized as privileged structures and useful templates for the design of diversified therapeutic molecules with potential pharmacological interest. Chromones and chromanones are widely distributed in plants and fungi, and significant biological activities, namely antioxidant, anti-inflammatory, antimicrobial, antiviral, etc., have been reported for these compounds, suggesting their potential as lead drug candidates. This review aims to update the literature published over the last 6 years (2018-2023) regarding the natural occurrence and biological activity of chromones and chromanones, highlighting the recent findings and the perspectives that they hold for future research and applications namely in health, cosmetic, and food industries.

Metal-modulated epitaxy of Mg-doped Al0.80In0.20N-based layer for application as the electron blocking layer in deep ultraviolet light-emitting diodes

This work reports the growth and characterization of p-AlInN layers doped with Mg by plasma-assisted molecular beam epitaxy (PAMBE). AlInN was grown with an Al molar fraction of 0.80 by metal-modulated epitaxy (MME) with a thickness of 180 nm on Si(111) substrates using AlN as buffer layers. Low substrate temperatures were used to enhance the incorporation of indium atoms into the alloy without clustering, as confirmed by X-ray diffraction (XRD). Cathodoluminescence measurements revealed ultraviolet (UV) range emissions. Meanwhile, Hall effect measurements indicated a maximum hole mobility of 146 cm2/(V∙s), corresponding to a free hole concentration of 1.23 × 1019 cm−3. The samples were analyzed by X-ray photoelectron spectroscopy (XPS) estimating the alloy composition and extracting the Fermi level by valence band analysis. Mg-doped AlInN layers were studied for use as the electron-blocking layer (EBL) in LED structures. We varied the Al composition in the EBL from 0.84 to 0.96 molar fraction to assess its theoretical effects on electroluminescence, carrier concentration, and electric field, using SILVACO Atlas. The results from this study highlight the importance and capability of producing high-quality Mg-doped p-AlInN layers through PAMBE. Our simulations suggest that an Al content of 0.86 is optimal for achieving desired outcomes in electroluminescence, carrier concentration, and electric field.

S-Dihydrodaidzein and 3-(1,3-benzoxazol-2-yl)-benzamide, Two New Potential β-estrogen Receptor Ligands with Anti-adipogenic Activity.

The elucidation of molecular pathways associated with adipogenesis has evidenced the relevance of estrogen and estrogen receptor beta (ERβ). The positive effects of ERβ ligands on adipogenesis, energy expenditure, lipolysis, food intake, and weight loss, make ERβ an attractive target for obesity control. From ligand-based virtual screening, molecular docking, and molecular dynamic simulations, six new likely ERβ ligands (C1 to C6) have been reported with potential for pharmacological obesity treatment. In this study, the effect of molecules C1-C6 on adipogenesis using the murine 3T3-L1 cell line was evaluated. Cell viability was assessed by MTT assays. Lipid accumulation and gene expression were investigated by ORO staining and real-time quantitative RT-PCR experiments, respectively. Cell viability was not significantly affected by C1-C6 at concentrations up to 10 μM. Interestingly, treatment with 10 μM of C1 (S-Dihydrodaidzein) and C2 (3-(1,3-benzoxazol-2-yl)- benzamide) for 72 h inhibited adipocyte differentiation; moreover, ORO staining evidenced a reduced intracellular lipid accumulation (40% at day 7). Consistently, mRNA expression of the adipogenic markers, PPARγ and C/EBPα, was reduced by 50% and 82%, respectively, in the case of C1, and by 83% and 59%, in the case of C2. Altogether, these results show the two new potential β-estrogen receptor ligands, C1 and C2, to exhibit anti-adipogenic activity. They could further be used as lead structures for the development of more efficient drugs for obesity control.