Valuable Scaffolds Research Articles

Teaching Transnational Asian American History Using a Human Rights Approach: Illustrating with Chinese American History

As an increasing number of states mandate or consider the incorporation of Asian American history into school curricula, educators and curriculum developers are actively responding to this growing demand. Recognizing the transnational nature of Asian American history and the explanatory power of Asian Critical (AsianCrit) Theory in addressing this complexity, I advocate for the pedagogical effectiveness of a human rights framework. This framework provides a valuable scaffold for students’ learning and the development of a transnational perspective. After reviewing multiple typologies of Human Rights Education, I propose that the C3 Inquiry framework offers a robust model for implementing Human Rights Education. This approach provides a comprehensive strategy for teaching about, through, and for human rights within the context of teaching and learning about Asian American history. To illustrate this approach, a sample unit plan focusing on key moments in Chinese American history is presented.

Indole Derivatives: A Versatile Scaffold in Modern Drug Discovery-An Updated Review on Their Multifaceted Therapeutic Applications (2020-2024).

Indole derivatives have become an important class of compounds in medicinal chemistry, recognized for their wide-ranging biological activities and therapeutic potential. This review provides a comprehensive overview of recent advances in the evaluation of indole-based compounds in the last five years, highlighting their roles in cancer treatment, infectious disease management, anti-inflammatory therapies, metabolic disorder interventions, and neurodegenerative disease management. Indole derivatives have shown significant efficacy in targeting diverse biological pathways, making them valuable scaffolds in designing new drugs. Notably, these compounds have demonstrated the ability to combat drug-resistant cancer cells and pathogens, a significant breakthrough in the field, and offer promising therapeutic options for chronic diseases such as diabetes and hypertension. By summarizing recent key findings and exploring the underlying biological mechanisms, this review underscores the potential of indole derivatives in addressing major healthcare challenges, thereby instilling hope and optimism in the field of modern medicine.

Aziridines as Versatile C(sp3) Precursors in Transition-Metal Catalyzed Cross-Coupling Strategies

Aziridines, which serve as valuable scaffolds in numerous pharmaceuticals and bioactive molecules, have emerged as highly efficient C(sp3) precursors in the realm of organic chemistry. Particularly, employing aziridines as versatile electrophiles in transition metal-catalyzed cross-coupling has enabled precise control over the regiochemistry in the formation of new C(sp3)-C, Si, B bonds. This review explores recent innovative aziridine cross-coupling approaches using Ni or Pd catalysis, highlighting initial findings of new mechanistic approaches and delineating distinct catalytic pathways.

A Review on Synthetic Thiazole Derivatives as an Antimalarial Agent.

Thiazole is a widely studied core structure in heterocyclic chemistry and has proven to be a valuable scaffold in medicinal chemistry. The presence of thiazole in both naturally occurring and synthetic pharmacologically active compounds demonstrates the adaptability of these derivatives. The current study attempted to review and compile the contributions of numerous researchers over the last 20 years to the medicinal importance of these scaffolds, with a primary focus on antimalarial activity. The review is based on an extensive search of PubMed, Google Scholar, Elsevier, and other renowned journal sites for a thorough literature survey involving various research and review articles. A comprehensive review of the antimalarial activity of the thiazole scaffold revealed potential therapeutic targets in Plasmodium species. Furthermore, the correlation of structure-activity-relationship (SAR) studies from various articles suggests that the thiazole ring has therapeutic potential. This article intends to point researchers in the right direction for developing potential thiazole-based compounds as antimalarial agents in the future.

Germacrone: A Multi-targeting Sesquiterpene with Promising Anti-cancer and Chronic Disease Applications.

Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease. This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction. A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities. Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics. The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts.

Exploration of Synthetic Potential of 2‐Chloro‐Quinoline‐3‐Carbaldehyde

Quinoline is one of the most important simple nitrogen heterocycles, being widespread in nature and present in a broad variety of pharmacologically active compounds. Specifically, quinoline is renowned antimalarial agents from several past decades and showed strong potential in this field. 3‐Formyl‐quinoline is a versatile precursor which transformed through the several easy methods into a wide range of biologically valuable scaffolds. The exploration of 3‐formyl‐quinoline gained much more attention to medicinal chemists in the field of drug discovery to design and synthesize new fused/tethered quinolines as potent therapeutical agents. The aim of this review, which covers the period from 2011 to 2023, is to update the role of formyl functionality of quinolines showing the extraordinary ability to play role in organic synthesis.

Crystal structures of coronaviral main proteases in complex with the non-covalent inhibitor X77

Main proteases (Mpros) are a class of conserved cysteine hydrolases among coronaviruses and play a crucial role in viral replication. Therefore, Mpros are ideal targets for the development of pan-coronavirus drugs. X77, previously developed against SARS-CoV Mpro, was repurposed as a non-covalent tight binder inhibitor against SARS-CoV-2 Mpro during COVID-19 pandemic. Many novel inhibitors with favorable efficacy have been discovered using X77 as a reference, suggesting that X77 could be a valuable scaffold for drug design. However, the broad-spectrum performance of X77 and underlying mechanism remain less understood. Here, we reported the crystal structures of Mpros from SARS-CoV-2, SARS-CoV, and MERS-CoV, and several Mpro mutants from SARS-CoV-2 variants bound to X77. A detailed analysis of these structures revealed key structural determinants essential for interaction and elucidated the binding modes of X77 with different coronaviral Mpros. The potencies of X77 against these investigated Mpros were further evaluated through molecular dynamic simulation and binding free energy calculation. These data provide molecular insights into broad-spectrum inhibition against coronaviral Mpros by X77 and the similarities and differences of X77 when bound to various Mpros, which will promote X77-based design of novel antivirals with broad-spectrum efficacy against different coronaviruses and SARS-CoV-2 variants.

Exploitation of pyrazole C-3/5 carbaldehydes towards the development of therapeutically valuable scaffolds: a review

Exploitation of pyrazole C-3/5 carbaldehydes towards the development of therapeutically valuable scaffolds: a review

Pyrazolidinone-Aided Ru(II)-Catalyzed Regioselective C-H Annulation with Allenes.

Regioselective annulation of allenes via C-H activation represents an elegant synthetic approach toward the construction of valuable scaffolds. Considering the importance of allenes, herein we developed an unprecedented Ru(II)-catalyzed highly regioselective redox-neutral C-H activation/(4 + 1)-annulation of 1-arylpyrazolidinones employing allenyl acetates to access pyrazolo[1,2-a]indazol-1-one derivatives. Additionally, allenyl cyclic carbonates, which were never tested in C-H activation, were utilized to construct a similar class of heterocycles having a pendent alcohol functionality. Notably, double C-H functionalization was achieved by a simple modification of reaction conditions. The synthetic significance of this methodology is underscored by late-stage modification of natural products, broad substrate scope, gram-scale synthesis, and postfunctionalizations.

Synthesis of Azo-Substituted Bicyclo[1.1.1]pentanes (BCPs) via Base-Promoted Halogen Atom Transfer.

Because of the three-dimensional bioisosteric feature, bicyclo[1.1.1]pentylamines (BCPAs) are valuable scaffolds in synthetic chemistry and medicinal chemistry. Here, we report a Halogen Atom Transfer (XAT) mediated radical C-N coupling between C3-iodo-BCPs and diazonium salts in the presence of base. Similarly, a multicomponent reaction (MCR) enables the simultaneous construction of the C-C bond and C-N bond simultaneously. Versatile roles of diazonium salts were also explored.

Recent Advances in the Use of 2‐Aminobenzyl Alcohols in the Synthesis of Quinolines, Quinazolines and Other N‐Heterocycles

AbstractN‐Heterocyclic compounds, in particular, quinolines and quinazolines are frequently used in medicinal chemistry. Therefore, the direct and clean synthesis of these valuable scaffolds has been a great interest for many years. 2‐Aminobenzyl alcohols as an alternative reactant instead of unstable and expensive 2‐aminobenzaldehydes can be used in the construction of N‐fused heterocycles including quinolines, quinazolines, oxazines, thiazines, selenazines, imidazoles, diazepines, etc. In this review article, we have discussed recent developments in the use of 2‐aminobenzyl alcohols in the synthesis of diverse heterocycles.

Therapeutic applications of carbohydrate-based compounds: a sweet solution for medical advancement.

Carbohydrates, one of the most abundant biomolecules found in nature, have been seen traditionally as a dietary component of foods. Recent findings, however, have unveiledtheir medicinal potential in the form of carbohydrates-derived drugs. Their remarkable structural diversity, high optical purity, bioavailability, low toxicity and the presence of multiple functional groups have positioned them as a valuable scaffold and an exciting frontier in contemporary therapeutics. At present, more than 170 carbohydrates-based therapeutics have been granted approval by varying regulatory agencies such as United States Food and Drug Administration (FDA), Japan Pharmaceuticals and Medical Devices Agency (PMDA), Chinese National Medical Products Administration (NMPA), and the European Medicines Agency (EMA). This article exploresan overview of the fascinating potential and impact of carbohydrate-derived compounds as pharmacological agents and drug delivery vehicles.

Synthesis and evaluation of novel ring-conjugated coumarins as biosafe broad-spectrum antimicrobial candidates

This study presents, for the first time, the synthesis of innovative conjugates identified as a five-membered ring integrating three heteroatoms linked linearly to the coumarin framework. Seven conjugates, comprising combinations of 1,3,2-dioxathiole-2-oxide and coumarin derivatives, were made via a three-stage synthetic procedure originating from benzene 1,2,4-triole. Spectroscopic methodologies, encompassing 1H-NMR, 13C-NMR, and FTIR, were utilized to validate the structural frameworks of the synthesized conjugates. Their capacity in the biomedicine field to act as broad-spectrum antimicrobial agents was evaluated. Furthermore, the biosafety and in silico pharmacokinetic characteristics of the conjugates were also examined. Six pathogenic aerobic bacteriomers, three anaerobic bacteriomers, and two fungiomers were utilized to investigate the broad-spectrum antimicrobial activity of the conjugates. On the other hand, three non-pathogenic bacteriomers were employed to reveal the biosafety profiles of the synthesized conjugates. Finally, two web-based programs were utilized to unveil the pharmacokinetic profiles of the title conjugates. The authors outlined four principal outcomes drawn from the extracted results. The conjugation between 1,3,2-dioxathiole-2-oxide and coumarin derivatives demonstrates biosafety and broad-spectrum antimicrobial implications. Conjugate DOTC5 displayed potent antibacterial activity against the tested aerobic bacteriomers, showing a potency comparable to that of the reference drug. Conjugate DOTC1 demonstrated strong antifungal activity exceeding that of the standard used. The synthesized conjugates, particularly DOTC5, displayed interesting biosafety profiles against the non-pathogenic bacteriomers. It concluded that the conjugates DOTC5 and DOTC1 exhibit the potential to function as valuable scaffolds for developing novel medications with biosafe, broad-spectrum antimicrobial activities in the foreseeable future.

Five Himalayan weeds as potential bioresources for bioactive agents: toxic compounds to valuable scaffolds

Five Himalayan weeds as potential bioresources for bioactive agents: toxic compounds to valuable scaffolds

Facile Synthesis of Some New Peptidomimetic β3 -and β2,3 -Amino Alcohols Possessing Pyridyl Moiety via Reductive Ring Opening of Pyridyl-isoxazolidines.

Regio- and stereoselective 1,3-dipolar cycloadditions of C-(3-pyridyl)-N-phenylnitrone (2) with variedly substituted dipolarophiles (3, 4) were carried out to obtain substituted pyridyl-isoxazolidines (5-8). Reductive cleavage of pyridyl-isoxazolidines (5-8) with ammonium formate, methanol-THF solvents, at ambient temperature, in the presence of Pd/C provided a facile route for the synthesis of β3 -and β2,3 -amino alcohols (9-12), with a substitution pattern having pronounced influence on torsional angles. The obtained compounds (9-12) are valuable scaffolds which can be utilized for peptidomimetics. Thus, the present methodology for reductive opening of isoxazolidine ring avoids the disadvantages of using expensive apparatus and hazards involved in the use of hydrogen gas. The preferential formation of amino-alcohols in case of bicyclic isoxazolidines (8a-c), which precludes any recyclization is rationalized by DFT calculations.

Exploring enantiopure zinc-scorpionates as catalysts for the preparation of polylactides, cyclic carbonates, and polycarbonates.

New and simple ligand design strategies for the preparation of versatile metal-based catalysts capable of operating under greener and eco-friendly conditions in several industrially attractive processes are in high demand for society development. We present the first nucleophilic addition of an organolithium to ketenimines which incorporates a stereogenic centre in an N-donor atom to prepare new enantiopure NNN-donor scorpionates. We have also verified its potential utility as a valuable scaffold for chirality induction through the preparation of inexpensive, non-toxic and asymmetric zinc complexes. The pro-ligands and the corresponding zinc-based complexes have been characterized by X-ray diffraction studies. DFT studies were carried out to rationalize the different complexation abilities of these pro-ligands. These complexes have proved to act as highly efficient catalysts for a variety of sustainable bioresourced processes that are industrially attractive, with a wide substrate scope. Thus, complex 7 behaves as a highly efficient initiator for the well-behaved living ring-opening polymerization (ROP) of rac-lactide under very mild conditions. The PLA materials produced exhibited enhanced levels of isoselectivity, comparable to the highest value reported so far for zinc-based catalysts (Pi = 0.88). In addition, the combination of 7 with onium halide salts functioned as a very active and selective catalyst for CO2 fixation into five-membered cyclic carbonates through the cycloaddition of CO2 into epoxides under very mild and solvent-free conditions, reaching very good to excellent conversions (TOF = 227 h-1). Furthermore, this bicomponent system exhibits a broad substrate scope and functional group tolerance, including mono- and di-substituted epoxides, as well as the very challenging bio-renewable tri-substituted terpene-derived cis/trans-limonene oxide, whose reaction proceeds with high stereoselectivity. Finally, complex 7 also achieved high activity and selectivity as a one-component initiator for the synthesis of poly(cyclohexene carbonate)s via ring-opening copolymerization (ROCOP) of cyclohexene oxide and CO2 under very soft conditions, affording materials with narrow dispersity values.

Access to distal biaxial atropisomers by iridium catalyzed asymmetric C-H alkylation.

Distal biaxial atropisomers are typical structures in chiral catalysts and ligands and offer a wide variety of applications in biology and materials technology, but the development of efficient synthesis of these valuable scaffolds is still in great demand. Herein, we describe a highly efficient iridium catalyzed asymmetric C-H alkylation reaction that provides a range of new distal biaxial atropisomers with excellent yields (up to 99%) and stereoselectivity (up to 99% ee and essentially one isomer). Based on this unprecedented strategy, a polycyclic skeleton with five successive chiral centers as well as C-C and C-N (or N-N) two distal chiral axes was created successfully in mild circumstances. In addition, the optically pure products bearing fluorophores show circular polarized luminescence (CPL) properties, being potential candidate materials for CPL applications.

Elucidating molecular mechanisms of protoxin-II state-specific binding to the human NaV1.7 channel.

Human voltage-gated sodium (hNaV) channels are responsible for initiating and propagating action potentials in excitable cells, and mutations have been associated with numerous cardiac and neurological disorders. hNaV1.7 channels are expressed in peripheral neurons and are promising targets for pain therapy. The tarantula venom peptide protoxin-II (PTx2) has high selectivity for hNaV1.7 and is a valuable scaffold for designing novel therapeutics to treat pain. Here, we used computational modeling to study the molecular mechanisms of the state-dependent binding of PTx2 to hNaV1.7 voltage-sensing domains (VSDs). Using Rosetta structural modeling methods, we constructed atomistic models of the hNaV1.7 VSD II and IV in the activated and deactivated states with docked PTx2. We then performed microsecond-long all-atom molecular dynamics (MD) simulations of the systems in hydrated lipid bilayers. Our simulations revealed that PTx2 binds most favorably to the deactivated VSD II and activated VSD IV. These state-specific interactions are mediated primarily by PTx2's residues R22, K26, K27, K28, and W30 with VSD and the surrounding membrane lipids. Our work revealed important protein-protein and protein-lipid contacts that contribute to high-affinity state-dependent toxin interaction with the channel. The workflow presented will prove useful for designing novel peptides with improved selectivity and potency for more effective and safe treatment of pain.

Development of Dual Inhibitors of Soluble Epoxide Hydrolase/Fatty Acid Amide Hydrolase with Tetrazole Core.

The attractive biological actions of the eicosatrienoic acids (EETs) and endocannabinoids (eCBs) are terminated by means of enzymatic hydrolysis via soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) enzymes. Simultaneous inhibition of both enzymes is considered a novel approach in the treatment of inflammatory and neuropathic pain. In this study, a novel series of tetrazole derivatives as dual sEH/FAAH inhibitors were designed, synthesized, and biologically evaluated. Compounds 6c, 7d, and 8a, the most potent inhibitors against FAAH and sEH enzymes with acceptable IC50 values, significantly decreased carrageenan- induced paw edema 5h after carrageenan injection compared to the control group compound. In addition, compound 7d exhibited a significant reduction in pain scores compared to the control group. Docking studies showed that the presented dual inhibitors could bind to the essential residues in the catalytic sites of both enzymes. In silico prediction of several pharmacokinetic properties suggests that these dual inhibitors could potentially be orally active agents. These structures will be a valuable scaffold to develop soluble epoxide hydrolase inhibitors with dual potency towards fatty acid amide hydrolase.

Transition‐Metal‐Catalyzed Cyclization of Alkenyl Iodide

AbstractAlkenyl iodide, as an essential precursor and structural unit in organic synthesis, has been widely used in the synthesis of natural products, pharmaceutical pesticides and functional materials. The high reactivity of the Csp2−I bond enables the formation of a C−M bond through oxidative addition, followed by subsequent transformations of the C−M bond to create new chemical bonds. A variety of valuable scaffolds, in particular the cyclic motifs, could be achieved via designing and synthesis the corresponding alkenyl iodide, which makes this strategy to be a hot topic in synthetic chemistry. In this paper, the recent progresses of transition metal‐catalyzed cyclizationof alkenyl iodides are summarized, and the possible mechanisms for most transformations are described in detail.