Compounds 4n Research Articles

Design, Synthesis and in Silico Molecular Docking Studies of Adamantanyl hydrazinylthiazoles as Potential Anti-diabetic Agents.

Diabetes mellitus is a widespread disease that poses a major threat to millions of people. To address this issue, we have synthesized seventeen new 4-(adamantan-1-yl)-(2-(arylidene)hydrazinyl)thiazolesvia Hantzsch synthetic approach. The molecular structures of all the compounds were confirmed using spectroscopic techniques. Protein kinase, α-amylase, glycation, and oxidation inhibition potential of all compounds were also investigated and it was found, compounds 3b, 3c, 3e-3g and 3i-3q have shown excellent α-amylase inhibition (IC50= 7.91 ± 0.07 to 28.57 ± 0.1 µM), compounds 3c, 3e, 3i, 3k and 3p (IC50= 30.6 ± 0.06 to 37.8 ± 0.005 ppm) were found to be highly potent anti-glycating agents and compounds 3c, 3g, 3h, 3k, and 3m were found more potent protein kinase inhibitors. The compounds 3b, 3c, 3d, 3e, 3f, 3g, 3i, 3k, 3l, 3m, 3n, 3p and 3q have shown good antioxidant potential (IC50= 27.5 ± 0.09 to 48.8 ± 0.09 µM). The biocompatibility of all samples was also tested by employing brine-shrimp lethality and in-vitro hemolytic assays and was found to be safe to human erythrocytes at tested concentrations. Furthermore, the Molecular docking simulation study also revealed that almost all synthesized compounds have potential interactions with target proteins at the molecular level.

Synthesis and antifungal activity of arecoline derivatives containing amino acid fragments.

A series of new arecoline derivatives containing amino acid fragments were synthesized, and their fungicidal activities were investigated. All synthesized compounds were characterized by 1H NMR, 13CNMR, and HRMS. Preliminary bioactivity assays demonstrated that Compounds 3k, 3n, 3p, 3q, 3r, and 3s exhibited significant antifungal activity against Botryosphaeria cactivora, Botryosphaeria dothidea, and Fusarium pseudograminearum at a concentration of 100μg/mL. Among them, Compound 3s displayed the highest inhibitory activity against Botryosphaeria dothidea (96.63%), surpassing the commercial fungicide chlorothalonil (91.30%). To explore the underlying mechanisms of the compounds, preliminary investigations into the antifungal mechanism involved molecular docking study, scanning electron microscopy and fluorescence microscopy observations, assessments of membrane permeability, and measurements of malondialdehyde content were carried out, respectively. The findings demonstrated that Compound 3s effectively inhibits fungal hyphal growth by compromising the integrity of the hyphal cell membrane. These results indicate that arecoline derivatives containing amino acid benzyl esters have potential as promising fungicides.

Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity.

The main protease (Mpro) of SARS-CoV-2 is a key drug target for the development of antiviral therapeutics. Here, we designed and synthesized a series of small-molecule peptidomimetics with various cysteine-reactive electrophiles. Several compounds were identified as potent SARS-CoV-2 Mpro inhibitors, including compounds 8n (IC50 = 0.0752 μM), 8p (IC50 = 0.0887 μM), 8r (IC50 = 0.0199 μM), 10a (IC50 = 0.0376 μM), 10c (IC50 = 0.0177 μM), and 10f (IC50 = 0.0130 μM). Most of them additionally inhibited cathepsin L and were also active against SARS-CoV-1 and MERS-CoV Mpro. In Calu-3 cells, several inhibitors, including 8r, 10a, and 10c, displayed high antiviral activity in the nanomolar range without showing cellular toxicity. The cocrystal structure of SARS-CoV-2 Mpro in complex with 8p revealed covalent binding to the enzyme's catalytic residue Cys145 and showed specific, unprecedented interactions within the substrate binding pocket. Compounds 10c and especially 8n were effective against a panel of naturally occurring nirmatrelvir-resistant mutants, particularly E166V, and showed metabolic stability and additional favorable pharmacokinetic properties, making it a suitable candidate for further preclinical development.

Microwave-Assisted Synthesis of Bis-1,2,3-Triazole-Based Benzophenones, In Vitro Antimicrobial Activity, and Molecular Docking Studies.

In this work, we have adopted an easy route to synthesize bis-1,2,3-triazole-based benzophenone compounds via a 1,3-dipolar cycloaddition reaction (Click chemistry). All the target compounds achieved better yields through the microwave-assisted method than the conventional method. Target compound structures were confirmed on the basis of the IR, 1H NMR, 13C NMR, and HR mass analysis. Additionally, we have carried out in vitro antibacterial and antifungal activities with ciprofloxacin and fluconazole standard drugs, respectively. Compounds 5b, 5f, 5i, 5k, and 5n were antibacterial, whereas 5a, 5e, 5g, 5i, and 5k showed promising antifungal activity with respect to standard drugs. Further, a molecular docking study performed against DNA gyrase and lanosterol 14-alpha demethylase envisioned promising binding interactions with a good docking score.

Quinoline-thiosemicarbazone-1,2,3-triazole-acetamide derivatives as new potent α-glucosidase inhibitors

In this work, a novel series of quinoline-thiosemicarbazone-1,2,3-triazole-aceamide derivatives 10a-n as new potent α-glucosidase inhibitors was designed, synthesized, and evaluated. All the synthesized derivatives 10a-n were more potent than acarbose (positive control). Representatively, (E)-2-(4-(((3-((2-Carbamothioylhydrazineylidene)methyl)quinolin-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-phenethylacetamide (10n), as the most potent entry, with IC50 = 48.4 µM was 15.5-times more potent than acarbose. According to kinetic study, compound 10n was a competitive inhibitor against α-glucosidase. This compound formed the desired interactions with important residues of the binding pocket of α-glucosidase with favorable binding energy in the molecular docking and molecular dynamics. Compounds 10n, 10e, and 10 g as the most potent compounds among the synthesized compounds were evaluated in term of pharmacokinetics and toxicity via online servers. These evaluations predicted that compounds 10n, 10e, and 10 g had good pharmacokinetic properties and toxicity profile.

The antibacterial and anti-biofilm effects of novel synthetized nitroimidazole compounds against methicillin-resistant Staphylococcus aureus and carbapenem-resistant Escherichia coli and Klebsiella pneumonia in vitro and in silico

The antibiotic resistance and biofilm formation by bacterial pathogens has led to failure in infections elimination. This study aimed to assess the antibacterial and anti-biofilm properties of novel synthesized nitroimidazole compounds (8a–8o). In this study, nitroimidazole compounds were synthesized via the A3 coupling reaction of sample substrates in the presence of copper-doped silica cuprous sulfate (CDSCS). Fifteen and two carbapenemase producing Escherichia coli and Klebsiella pneumonia (CP-E. coli and CP-K. pneumonia, respectively) and one methicillin-resistant Staphylococcus aureus (MRSA) and one methicillin-susceptible S. aureus (MSSA) plus standard strain of each isolate were included. The antibacterial effects of these compounds demonstrated that the lowest minimum inhibitory and bactericidal concentrations (MIC/MBC, respectively) levels corresponded to compound 8g against S. aureus (1/2 µg/mL) and K. pneumonia (8/32 µg/mL) standard and clinical strains and confirmed by in silico assessment. This was comparable to those of metronidazole being 32–128 µg/mL against K. pneumonia and 32–64 µg/mL against S. aureus. In comparison to metronidazole, against CP-E. coli, compounds 8i and 8m had significantly higher antibacterial effects (p < 0.001) and against CP-K. pneumonia, compounds 8a–8j and 8l–8o had significantly higher (p < 0.0001) antibacterial effects. Compound 8g exhibited significantly higher antibacterial effects against MSSA and compounds 8b (p < 0.001), 8c (p < 0.001), 8d (p < 0.001), 8e (p < 0.001) and 8g (p < 0.0001) exerted significantly higher antibacterial effects than metronidazole against MRSA. Moreover, potential anti-biofilm effects was corresponded to compounds 8a, 8b, 8c, 8e, 8f, 8g, 8i, 8k, 8m and 8n. Considering the antibacterial and anti-biofilm effects of novel synthesized compounds evaluated in this study, further assessments is warranted to verify their properties in vivo and clinical trials in the future.

Acetylcholinesterase/butylcholinesterase Inhibitory Activities of Substituted Chromenone Derivatives

3,6-Disubstituted-2H-2-chromenones 3a-l and 3,4,6-trisubstituted 2H-2-chromenones 3m &amp; 3n were synthesized from 5-bromosalicylaldehyde 1 and 5-bromo-2-hydroxyacetophenone 5. Suzuki coupling of 5-bromosalicylaldehyde with various phenylboronic acids yielded 5-substituted salicylaldehydes 2b-l and these compounds were reacted with various β-ketoesters in presence of piperidine afforded substituted chromenone derivatives 3a-l in very good yields. The compounds 3m &amp; 3n were prepared by Suzuki coupling of 2m. Synthesized compounds 3a-n were screened for in vitro AChE &amp; BuChE activities and found that the compound 3n shown significant activity where as 3g, 3h, 3j, 3k &amp; 3m compounds were shown moderate activity of AChE. The compound 3d shown potent activity, where as 3c &amp; 3m shown moderate activity of BuChE and the results were compared with the standard drug Galanthamine.

Synthesis of Fused 1,2,3‐Triazoles of Benzimidazole Using Copper (I) Catalysis; in Vitro and in Silico Studies

AbstractIn this study, we described the synthesis of some new benzimidazole‐1,2,3‐triazole hybrids (4a–n) using well‐known copper‐catalyzed CuAAC and C─H arylation cascade reactions. We validated the structures of all compounds by using 1H NMR, 13C NMR, and mass spectrometry. In vitro assessment of anticancer efficacy against breast cancer cells, such as MCF‐7 and MDA‐MB‐468, demonstrated that compounds 4d, 4e, and 4f had superior activity comparable to the standard drug Erlotinib. Furthermore, compounds 4d, 4e, and 4f have the highest inhibitory efficacy against the tyrosine kinase EGFR, relative to the reference drug Erlotinib. Molecular docking investigations of the effective compounds 4d, 4e, 4f, and 4n with EGFR showed a greater affinity for the target protein. Furthermore, the in silico pharmacokinetic profile of the potent compounds 4d, 4e, 4f, and 4n was determined by using SWISS/ADME and pkCSM, and all the four compounds obeyed Lipinski, Ghose, Veber, Egan, and Muegge guidelines without any variation.

Design, synthesis and biological evaluation of some imidazo[1,2-a]pyridine derivatives as anti-tubercular agents: an in silico – in vitro approach

In this study, we designed, synthesized and evaluated some novel imidazo[1,2-a]pyridine derivatives as potential anti-TB agents. Preliminary in vitro screening for anti-TB activity of the synthesized compounds was performed against H37Rv strain using the microplate Alamar Blue assay (MABA). Network pharmacology was used to identify the possible targets and pathways of these compounds against Mtb infection. Molecular docking and molecular dynamics simulations were also performed to investigate the binding modes and stability of these compounds with the selected targets. The results showed that some of the synthesized compounds (6b, 6c, 6e, 6f, 6h, 6i, 6j, 6n and 6o) exhibited potent anti-TB activity, with minimum inhibitory concentrations (MICs) ranging from 1.6 to 6.25 μg/mL. The network pharmacology analysis revealed that among the 455 putative targets of imidazo[1,2-a]pyridine derivatives, 24 targets are the potential targets for treatment of Mtb infection. Among these 24 targets, 10 hub-targets were identified (TLR4, ICAM1, TLR9, STAT3, TNFRSF1A, ERBB2, CXCR3, ACE, IKBKG and NOS2) which were significantly involved in GO processes such as positive regulation of DNA-binding transcription factor activity, peptidyl-tyrosine phosphorylation, positive regulation of inflammatory response, mononuclear cell proliferation, regulation of hemopoiesis and cytokine production involved in inflammatory response and KEGG pathways such as pathways in Tuberculosis, NF-kappa B signalling, HIF-1 signalling PD-L1 expression, and PD-1 checkpoint pathway in cancer. Molecular docking and dynamics simulations confirmed the stable interactions of imidazo[1,2-a]pyridine derivatives with core target active sites, highlighting their potential as novel anti-TB drug candidates.

Novel Hydrazide-Hydrazones Bearing a Benzimidazole Ring: Design, Synthesis, and Evaluation of Inhibitor Properties Against CA I and CA II Isozymes.

In this study, we propose identifying potential novel compounds targeting carbonic anhydrase I and II. Herein, we have designed and synthesized new benzimidazole-hydrazide-hydrazones derivatives (4a-4r) to investigate the effects of these synthesized compounds on CA isoenzymes. The compounds' 1H NMR, 13C NMR, and HRMS spectra were used to confirm their chemical structures. The synthetic derivatives were screened for their inhibitory potential against carbonic anhydrase I and II by invitro assay. These compounds have IC50 values of 3.727-1.493 μM (hCA I) and 3.892-1.547 μM (hCA II). Inhibition types and Ki values of the compounds were determined. The Ki values of the compounds were 3.006 ± 0.17 μM-0.356 ± 0.0 μM (hCA I) and 2.923 ± 0.15 μM-0.346 ± 0.0 μM (hCA II). Acetazolamide (AAZ) was used as the reference in the study. The most potent derivatives, a 4-methoxy derivative (compound 4k) and 4-(trifluoromethyl) derivative (compound 4g), than AAZ (IC50 = 2.26 μM) and their IC50 values were found as 1.493 μM and 1.675 μM, respectively. Compared to AAZ, the other derivatives having more effect on hCA I were compounds 4b, 4e, 4l, 4m, 4n, and 4o. The compounds gave IC50 values of 1.743, 1.789, 1.933, 1.966, 1.983, and 1.986 μM, respectively. Compounds 4a-4r found no more effective inhibitory activity against hCA II isozyme than AAZ (IC50 = 1.17 μM). According to the invitro test results, detailed protein-ligand interactions of the compounds 4b and 4k exhibited considerably low binding energies, suggesting strong interaction affinities against hCA I. In addition, the cytotoxic effects of the compounds on the L929 healthy cell line were evaluated.

Novel Cephalosporins Against the Main Protease of SARS CoV (Mpro O, MproWT): Molecular Docking and DFT Study

AbstractOur study predicts potential inhibitors targeting nucleophilic catalytic dyed residues H41 and C145 of Mpro WT and Mpro omicron (Mpro O) following drug designing method protocols. Docking studies were used to find potent and efficient inhibitors that can compete with ATP for binding to a particular target protein location. Both proteins' structures were docked against library of cephalosporin derivatives, that is, Mpro WT and Mpro omicron are predicted with binding energy (ΔG bind‐PB) in range −11.501 to −14.8396 kcal/mol. It has been discovered that several kinds of residues, particularly His41, Cys145, Gly143, Gln189, His132, and Gln109, are necessary for the continual existence of inhibitors in the active pocket. DFT studies were also carried out to calculate optimized geometries, energies of HOMO–LUMO, MEP, and global chemical reactivity descriptors were obtained. In addition, the 1H‐NMR chemical shift of compounds was calculated using the GIAO method; the shifts of the molecules are in good agreement with the experimental value. In this series, compound 3N has the lowest ∆E value (3.31 eV) and compound 3C has the highest ∆E value (3.66 eV) showing them the most and the least reactive, respectively. According to this research, these ligands appear to have a bright future as SARS‐CoV‐2 treatment drugs.

Docking and Simulation Studies on Novel Analogues of 3,4,5-Trihydroxy Benzoic Acid as HSP90Alpha Inhibitors

HSP90 assists as a crucial molecular chaperone that responds to environmental stressors and helps in the survival of cells in microorganisms. This protein is integral to the stress response, aiding in the stabilization of various proteins essential for microbial survival. Consequently, the ability of a number of tissues to adjust to endogenous stress depends critically on appropriate chaperone activity. Modulators of chaperone activity, however, have emerged as a novel and developing area of drug discovery due to the association between changed chaperone function and the development of numerous illnesses. Inhibition of HSP90alpha can disrupt proper protein folding, thus impairing growth and virulence in fungi. In this work, we selected novel leads of gallic acid derivatives with the help of OSIRIS Property Explorer and DruLiTo software. Selected leads were subjected to ADME-T studies for further screening. Docking and molecular simulation studies on selected compounds were performed using Schrodinger v21 and GROMACS software to predict the bioactivity of novel leads of 3,4,5 trihydroxy benzoic acid for suppression of the HSP90alpha enzyme. Compounds 4N, 18N, 15N, and 14N showed good docking scores of -6.5, -6.4, -5.91, and -5.98, respectively, which was comparable to standard ciprofloxacin. Compound 4N and compound 14N demonstrated notable binding interactions and were selected for further investigation through molecular dynamics studies with HSP90alpha (PDB ID: 1YC1). RMSD, H BOND, and RMSF analysis confirmed the stable binding of compounds 4N and 14 N with the HSP90 enzyme. The RMSF plot showed less than 0.35 nm fluctuation for the HSP90alpha enzyme in complex with different ligands. It can be concluded that ligand binding can cause stability to the conformation of the protein. Compounds 4N and 14N are considered to be the best theoretical lead, which can further be studied experimentally as HSP90 alpha inhibitors for antimicrobial activity.

Microwave‐Assisted Fe3O4 Nanoparticles Catalyzed Cascade Synthesis of 3‐(1,4,5‐Triaryl‐1H‐imidazol‐2yl)quinolin‐2‐amines as COX‐1, COX‐2 Inhibitors and Antioxidant Agents

ABSTRACTA proficient Fe3O4 nanoparticle catalyzed cascade multicomponent synthetic protocol has been established to synthesize the title compounds. 2‐Chloroquinoline‐3‐carbaldehydes, aniline, and substituted benzils were subjected to cascade coupling to produce novel 3‐(1,4,5‐triaryl‐1H‐imidazol‐2‐yl)quinolin‐2‐amine 5k–z under microwave irradiation using Fe3O4 NPs. According to the biological data and the computational analysis, the compounds were found to bind COX‐2 enzyme superior than the COX‐1 enzyme. The molecular docked positions of the compounds (PDB ID: 4O1Z and PDB ID: 5IKR; A chain) were examined, and the results showed that these configurations are similar to those of the highly selective COX‐1 and COX‐2 inhibitors. Compared to mefenamic acid (1.318 μg), the compounds 5k, 5l, 5n, 5p, 5q, 5r, 5s, 5t, 5v, 5x, and 5z Showed IC50 values of 1.172, 1.136, 1.508, 1.0373, 1.186, 1.017, 1.827, 1.008, 1.504, 1.217, 1.440, and 1.832, respectively, making them the most effective and selective COX‐1 and COX‐2 inhibitors. For every significantly active molecule, a selectivity index was calculated. Interestingly, these molecules that worked as COX inhibitors also functioned well and showed promising results for antioxidant activity.

Structure–activity relationship studies of Imidazo[1′,2′:1,6]pyrido[2,3-d]pyrimidine derivatives to develop selective FGFR inhibitors as anticancer agents for FGF19-overexpressed hepatocellular carcinoma

The aberrant activation of fibroblast growth factor (FGF) and FGF receptor (FGFR)-mediated signaling pathways are associated with cancer development, including hepatocellular carcinoma (HCC). A novel series of imidazo[1′,2′:1,6]pyrido[2,3-d]pyrimidine, containing an acrylamide covalent warhead, were synthesized as selective FGFR 1–4 inhibitors. Compound 7n was identified as the most potent inhibitor against FGFR1, 2, and 4, with IC50 values of 8/4 nM (FGFR1/2) and 3.8 nM (FGFR4), and the covalent docking analyses suggested that 7n form a covalent adduct with cysteine residue on the hinge or p-loop of FGFR. Compound 7n exhibited a favorable pharmacokinetic profile and significant in vivo antitumor efficacy in human liver cancer xenograft mouse models (xenograft, FGF/FGFR-dependent HCC cells).

Ionic Liquid Assisted Green Synthesis of Quinoxaline Based Bisspirooxindoles: Anticancer Evaluation and Molecular Dynamics

AbstractIn this study, we have synthesized a series of novel quinoxaline based bisspirooxindoles through green protocol using ionic liquid [Bmim]BF4. All the compounds were well characterized by spectroscopic methods like FT‐IR, 1H NMR, 13C NMR, mass and finally the structures were authenticated by single crystal X‐ray diffraction (SCXRD) (4e). The target compounds were evaluated for their anticancer activity with different cancer cell lines like MDAMB‐231, MCF‐7, MCF‐10A, HCC‐1395, Molt‐4, and FaDU. The compounds 4d, 4g, 4m, and 4n showed 42.0%, 43.3%, 52.7%, and 56.0 percentage of growth inhibition respectively with the T cell acute lymphoblastic Molt‐4 cell line. The compounds 4b, 4c, 4 h, 4k, and 4m have shown 30%–39% of growth inhibition against FaDU cell line. Further, anticancer activity was validated with in silico molecular docking and molecular dynamics simulations. The outcomes of dynamics simulations exclusively emphasize that the compounds bind to HIS862 and TYR896 residues which are among the catalytic triad of PARP1. Finally, the results of ADME is also used to assess the drug likeness, which clearly shows that our target compounds are adaptable as potential drug pathways for medicinal chemists.

Design and Synthesis of Ester Linked 1,2,3‐Triazole Quinoline Derivatives with Pancreatic β Cells Protective Activity against Oxidative Stress and Endoplasmic Reticulum Stress for Better Management of Type II Diabetes Mellitus

AbstractUnresolved endoplasmic reticulum (ER) stress and oxidative stress lead to the pathogenesis of type II diabetes mellitus (DM). Connecting links between the ER stress and oxidative stress pathways might play an important role in treatment and pathogenesis of diabetes. Here, we used network pharmacology approach to find the target proteins linking the ER stress and oxidative stress pathways. CHOP emerged as a hub protein from our results and was targeted by 16 newly designed and synthesized ester linked 1,2,3‐triazole quinoline derivatives by molecular docking. Drug likeliness prediction studies revealed all compounds as good druggable candidates. Compounds 5b (R = H, R1 = F), 5j (R = CH3, R1 = F), 5m (R = OCH3, R1 = H), and 5n (R = OCH3, R1 = F) were found to have considerable binding energies and active site amino acid interactions with CHOP. We further showed that compounds 5b, 5m, and 5n exhibited low toxicity with more than 50% cell survival and low IC50 values. These were therefore subjected to evaluate their effects on ER stress and oxidative stress. Finally, compound 5n (R = OCH3, R1 = F) was found to alleviate ER stress and is also a good antioxidant. Identification of such targets and compounds effective in improving ER stress and oxidative stress may provide new insights in the development of therapies and management of T2DM.

Microwave expedited Cu(I) catalyzed regioselective 1,2,3-triazoles as Mycobacterium Tuberculosis H37Rv inhibitors, in vitro α-amylase and α-glucosidase inhibition, in silico studies

In the present study, an efficient and convenient synthesis of novel 1,2,3-triazoles (8i-t) incorporated quinoline and coumarin cores has been reported. Microwave-assisted Huisgen 1,3-dipolar cycloaddition reaction of azide and alkyne resulted in high yields (88–94 %) of the title compounds. Regioselective single-product formation both under conventional and microwave methods is the foremost supremacy of this work. All the molecules were subjected to in vitro antibacterial assessment wherein the compounds 8i, 8k, 8l, 8n, and 8r demonstrated very good antibacterial activity against other bacterial strains tested. Compounds 8i, 8k, 8l, 8n, 8o, 8q, and 8r demonstrated excellent antitubercular activity with MICs in the range 1.60–6.25 µg/mL in comparison to the standard drugs (Isoniazid-1.60 µg/mL, Ciprofloxacin-3.25 µg/mL, Pyrazinamide-6.25 µg/mL). Compounds 8i, 8n, and 8r also exhibited inhibitory effects against α-amylase and α-glucosidase and thus, also showed anti-diabetic activity. The significantly active compounds were subjected to molecular docking and molecular dynamics simulation studies to study the putative binding pattern as well as the stability of the docked complexes, respectively. In silico ADME profiles of the titled compounds were also predicted to access the drug-likeness properties of the designed compounds. Titled compounds showed potential effectiveness as antibacterial and antidiabetic agents.

Semi-Preparation and X-ray Single-Crystal Structures of Sophocarpine-Based Isoxazoline Derivatives and Their Pesticidal Effects and Toxicology Study.

Recently, research and development of novel pesticides from natural plant products have received much attention. To accelerate the application of sophocarpine as the agrochemical candidate, a series of novel sophocarpine-based isoxazoline derivatives were prepared by the 1,3-dipolar [2 + 3] cycloaddition reaction of sophocarpine with different chloroximes. Their structures were well characterized by high-resolution mass spectra, infrared spectra, and proton/carbon-13 nuclear magnetic resonance spectra. Eight steric configurations of compounds 5a, 5e', 5f, 5g, 5h, 5i, 5r, and 5u' were further determined by X-ray single-crystallography. Against Aphis citricola Van der Goot, compounds 5n (LD50: 0.032 μg/nymph) and 5o (LD50: 0.024 μg/nymph) exhibited greater than 3.7- and 4.9-fold potent aphicidal activity compared to sophocarpine (LD50: 0.118 μg/nymph). Against Tetranychus cinnabarinus Boisduval, derivative 5g displayed the most promising acaricidal activity with the LC50 value of 0.247 mg/mL, which was 14.2-fold that of sophocarpine. Compounds 5d and 5g also exhibited good control efficacy against T. cinnabarinus. Scanning electron microscopy images indicated that compound 5g can destroy the mite cuticle layer. These results will provide the foundation for the structural modification and use of sophocarpine derivatives as agrochemicals in the future.

Tandem Synthesis of Piriqualone and Analogues Using Deep Eutectic Solvents: Photophysical and Theoretical Insights

This study presents a sustainable chemical approach for the tandem synthesis of Piriqualone a sedative and anxiolytic drug and its analogues using a green protocol. The research investigates the ability of deep eutectic solvents (DESs) to act as catalysts as well as solvent in a tandem reaction involving metal‐free dehydrogenation and sp3 C‐H bond functionalization, leading to the formation of styryl‐heterocyclic compounds (7a‐p). These styryl derivatives were thoroughly characterized through spectral analysis and photophysical property evaluation. The relationship between chemical structure and AIE properties was particularly examined for compound 7n. Additionally, the experimental findings were corroborated by density functional theory (DFT) calculations. The structures of compounds 7j, 7p and 7fa were further validated through single crystal X‐ray diffraction (XRD) analysis.

Synthesis and antifungal activities of small molecule arylthiazolamine derivatives.

Developing new fungicides to compensate for the deficiencies of existing fungicides resistance in phytopathogenic fungi is a research hotspot in the field of pesticides. Aiming to discover novel template small molecules with excellent antifungal activity, thirty-eight arylthiazolamine derivatives were synthesized through bromination, cyclization, halogenation, and acylation reactions. The synthesized compounds were screened for antifungal activity against ten typical fungal pathogens, and some halogenated arylthiazolamines and amides exhibited excellent broad-spectrum antifungal activity, especially compounds 4m (3.96-47.76μg/mL), 5k (0.10-7.70μg/mL) and 5n (2.08-11.21μg/mL). Among them, compound 5k provided comparable protection and curative effects to chloroticonil and boscalid against B. dothidea and V. mali infection in apple and apple tree branches, respectively, and it could exert antifungal effects by inhibiting the differentiation of mycelium spores, spore germination, and bud tube growth. This study provides high-efficiency and inexpensive candidate compounds for managing of diseases caused by plant pathogenic fungi.