Compounds 4h Research Articles

Discovery of novel dihydro-pyrimidine hybrids: insight into the design, synthesis, biological evaluation and absorption, distribution, metabolism and excretion studies.

Aim: By keeping in aspects, the pharmacological potential of heterocyclic compounds, pyrimidine-based compounds were designed, synthesized and evaluated for α-amylase inhibitory potential.Materials & methods: Five new series 1a-l, 2a-d, 3a-d, 4a-d and 5a-d of 1,2,3,4-tetrahydroprimidine-5-carboxylate derivatives were designed by de novo method by taking Alogliptin as reference compound. Here in we describe synthesis and characterization of compounds as potential α-amylase inhibitor.Results: Structure activity relationship (SAR), in vitro analysis and molecular modelling approaches generate compounds 1h, 1i, 1k and 4c as potential lead with good α-amylase inhibitory selection. However, compound 1k failed the criteria of optimization as drug lead by ADME studies while all other compounds showed optimum range for all in silico ADME parameters.Conclusion: Therefore, these compounds can serve as potential lead candidate in developing anti-diabetic therapy.

Synthesis, antibacterial, anti-urease, DFT and molecular docking studies of novel bis-1,3,4-thiadiazoles

A series of 2-substitutedamino-1,3,4-thiadiazoles (4a-4j) were synthesized starting from various isothiocyanate derivatives. The newly synthesized compounds were characterized by 1H NMR, 13C NMR, and elemental analysis. All compounds were tested for antibacterial activity against Proteus vulgaris (ATCC 7829) via the microbroth dilution technique. Among them, compound 4h emerged as the most potent antibacterial agent with MIC value of 4.1 μM. All synthetic compounds were additionally evaluated for their urease inhibitory activity and exhibited good inhibitory potential against urease with IC50 values in the range of 1.732 ± 0.186 - 3.786 ± 0.300 μM as compared to the standard thiourea (IC50 = 11.008 ± 0.932 μM). Compounds 4d, 4h and 4i showed significant inhibitory effects with IC50 values of 1.981 ± 0.265, 1.732 ± 0.186 and 1.937 ± 0.173 μM, respectively. In silico molecular docking study showed the critical interactions of compound 4h with the active site of the urease. According to DFT, compounds 4j and 4d (with low ΔE=4.536 eV and 4.629 eV values, respectively) are more chemically reactive than the other molecules, in which consistent with their inhibitory potentials against the urease enzyme. Molecular Dynamics simulations also were performed to assess the energetic features of the urease in complex with compound 4h. Furthermore, the predicted ADMET characteristics of the compound 4h was calculated using QikProp to gain insights into its pharmacokinetic properties. These newly identified inhibitors of the urease enzyme can serve as leads for further antibacterial drug research and development.

Exploring the anti-diabetic activity of benzimidazole containing Schiff base derivatives: In vitro α-amylase, α-glucosidase inhibitions and in silico studies

The current study explores the anti-diabetic potential of some Schiff bases containing benzimidazole scaffold. These derivative were synthesized by refluxing sodium metabisulfite with ethyl 2-(2-ethoxy-6-formylphenoxy)acetate followed by the addition of ortho phenylene diamine in DMF solvent to get the benzimidazole which was further refluxed in hydrazine hydrate to obtain the hydrazide. Finally various substituted benzaldehydes were treated with the desired hydrazide using a catalytic quantity of acetic acid to obtain the hydrazone Schiff bases. These compounds were evaluated for their ability to inhibit α-amylase and α-glucosidase inhibitory potentials. Among them, six derivatives including 2g, 2h, 2q, 2p, 2i, and 2m displayed noteworthy inhibitory activities against α-amylase (IC50 = 2.15 ± 0.17 µM to 15.18 ± 3.29 µM ) and α-glucosidase (IC50 = 4.21 ± 0.78 to 16.10 ± 0.52 µM) superior than the standard acarbose, while the remaining compounds showed significant to less inhibitory activities. By clarifying the mechanisms of interaction between the chemicals and amino acid residues, the molecular docking analysis attempted to shed light on the binding modalities of these molecules. The reactivity indices of these compounds were calculated using the Density Functional Theory (TD-DFT) approach, employing the B3LYP-d energy function and lacvp**(d,p) basis set for calculations. Schiff base derivatives based on benzimidazole, especially compounds 2h and 2g, exhibited lower electrophilicity and higher bioactivity compared to their counterparts 2i and 2m.

Assessing β-Carboline Analogues As Antibiotic Agent Using In Vitro Studies

The mortality rate caused by bacterial diseases and bacterial antimicrobial resistance (AMR) is a significant concern in global public health. There is an urgent demand for new therapeutic agents that not only offer improved efficiency but also entail fewer secondary effects, addressing the challenges posed by the currently available drugs used in clinical practice. In this study, 40 analogues of β-carboline were subjected to solubility tests to determine their solubility. Among them, 22 analogues proved to be soluble and were subsequently tested for in vitro antibacterial activity using the agar disc diffusion method against S. aureus and E. coli to evaluate their effectiveness. The results of the in vitro antibacterial studies revealed that compounds 1h, 7d, and 1l displayed appreciable growth-inhibitory effects against E. coli, while compounds 1a, 1f, 1l, and 1j exhibited appreciable growth-inhibitory effects against S. aureus. Notably, compounds 1j and 1l displayed the highest growth-inhibitory potency against S. aureus and E. coli, respectively, out of the 22 compounds tested. Of all the analogues examined, 1l and 1j demonstrated the most substantial growth-inhibitory effects against E. coli and S. aureus, respectively, underscoring their potential as inhibitors.

Diphenyl urea-benzylidene acetohydrazide hybrids as fibroblast growth factor receptor1 inhibitors and anticancer agents.

Molecular hybridization between diphenyl urea and benzylidene acetohydrazide was adopted for the design of a new series of FGFR-1 targeting cancer. The designed series was synthesized and submitted to NCI-USA to be screened for their growth inhibitory activity on NCI cancer cell lines. Some of the synthesized hybrids displayed promising growth inhibitory activity on NCI cancer cell lines with a mean GI% between 70.39% and a lethal effect. Compounds 9a, 9i, 9j, and 9n-p were further selected for a five-dose assay and all the tested candidates showed promising antiproliferative activity with GI50 reaching the submicromolar range. Encouraged by the potent activity of 9a on colon cancer on the one hand and the well-known overexpression of FGFR-1 in it on the other hand, it was further selected as a representative example to be evaluated for its mechanism on the cell cycle and apoptosis of HCT116 cell line. Interestingly, 9a was found to pause the cell cycle of the HCT116 cell line at the G1 phase and induced late apoptosis. In parallel, all the synthesized hybrids 9a-p were examined for their potential to inhibit FGFR-1 at 10 µM. Compounds 9a, 9g, 9h, and 9p were found to have potent inhibitory activity with % inhibition = 63.04%, 58.31%, 60.87% and 79.84%, respectively. Molecular docking simulation of 9a in the binding pocket of FGFR-1 confirms its capability to achieve the characteristic interactions of the type II FGFR-1 inhibitors. Exploration of the ADME properties of 9a-p by SwissADME web tool proved their satisfactory physicochemical properties for the discovery of new anticancer hits.

Molecular hybridization of pyridine-thiophene clubbed isoxazole heterocycle in a single entity: Synthesis, antimicrobial, antitubercular, molecular docking and ADMET analysis

In the present study, 10 new hybrid pyridine-thiophene clubbed isoxazole derivatives (8a-j) were synthesized from the reaction of benzylideneacetophenones (7a-j) with hydroxylamine hydrochloride in alkaline medium. The synthesized compounds were tested for in vitro antimicrobial and antitubercular properties. Four promising new lead compounds such as 8c, 8d, 8f, and 8h endowed with excellent antimicrobial and antitubercular activity. In addition, the docking score for the most active compounds 8b, 8e, 8g, and 8h was found to be -8.6 to -8.8 kcal/mol demonstrating its favorable accommodation within the active site of the PknB enzyme.. KEYWORDS :ADMET analysis, Antimicrobial, Antitubercular, Molecular docking, Molecular hybridization, Pyridine-thiophene clubbed isoxazole.

Synthesis of New Thiazole-Privileged Chalcones as Tubulin Polymerization Inhibitors with Potential Anticancer Activities.

A series of novel thiazole-based chalcones were evaluated for their anticancer activity as potential tubulin polymerization inhibitors. In vitro anticancer screening for the thiazole derivatives 2a-2p exhibited broad-spectrum antitumor activity against various cancer cell lines particularly Ovar-3 and MDA-MB-468 cells with a GI50 range from 1.55 to 2.95 μΜ, respectively. Compound 2e demonstrated significant inhibition of tubulin polymerization, with an IC50 value of 7.78 μM compared to Combretastatin-A4 (CA-4), with an IC50 value of 4.93 μM. Molecular docking studies of compounds 2e, 2g, and 2h into tubulin further supported these findings, revealing that they bind effectively to the colchicine binding site, mirroring key interactions exhibited by CA-4. Computational predictions suggested favorable oral bioavailability and drug-likeness for these compounds, highlighting their potential for further development as chemotherapeutic agents.

Design, synthesis and docking studies of new molecular hybrids bearing benzimidazole and thiazolidine-2,4-dione as potential antitubercular agents

Finding novel therapeutic medications to combat tuberculosis (TB) is crucial, as evidenced by the disease's growth as a worldwide health concern in recent decades and the rise of drug-resistant forms of Mycobacterium tuberculosis (Mtb). In this article, we describe the synthesis and design of a novel class of thiazolidine-2,4-dione derivatives (5a-i) based on 1H-benzo [d]imidazoles as antitubercular drugs. Spectroscopic techniques and elemental analysis were used to characterize each of the newly synthesized molecules. The antitubercular activity of all the newly synthesized title compounds was assessed against drug-sensitive Mtb H37Rv, multidrug-resistant (MDR-TB), and extensively drug-resistant (XDR-TB) tuberculosis. Compounds 5e and 5 h had the most antitubercular activity among all the newly synthesized hybrids against drug-sensitive, MDR-TB, and XDR-TB strains, with MIC values ranging from 0.21 to 47.84 μM. When it comes to drug-sensitive, drug-resistant, and XDR Mtb strains, compound 5 h with a trifluoromethyl group is 1.71, 10.86, and 3.50 times more potent, whereas compound 5e with a nitro group is 1.12, 8.50, and 2.61 times more active. Remarkably, the compounds' in vitro cytotoxicity test demonstrated good selectivity indices, highlighting their safety on the normal lung fibroblast (WI-38) cell line experiment. To further understand the interactions between potent hybrids and the target enzyme, molecular docking investigations were conducted against the decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1) enzyme. The target protein exhibited preferentially positive interactions with the potent compounds 5e, 5f, 5 h, and 5i. Relationships between structure-activity as well as drug-likeness were used to connect the freshly synthesized compounds' physical and biological properties. When considered collectively, these results suggest that compounds 5e and 5 h might be promising candidates for the development of drug-sensitive and drug-resistant TB therapies in the future.

Synthesis, Anti-Oomycete and Anti-Fungal Activities of Anhydride Derivatives of Oleanolic Acid.

Oleanolic acid is a pentacyclic triterpenoid extracted and isolated from the fruit of plants in the Ligustrum lucidum Ait. in the family Oleaceae. To discover biorational natural product-based pesticides, a series of oleanolic acid derivatives containing anhydride active skeletons were prepared by ingeniously introducing an active acyloxy group at its C-28 carboxyl position, and their structures were well characterized by 1H NMR, 13C NMR, HRMS, and m.p.. The stereochemical configuration of compound 8e was confirmed using single-crystal X-ray diffraction. Furthermore, bioactivities of these compounds as anti-oomycete and anti-fungal agents against two serious agricultural pests, Phytophthora capsici and Fusarium graminearum we assessed. Amongst evaluated compounds, 1) Compounds 8h and 8j displayed significant anti-oomycete against P. capsici, with EC50 values of 54.73 and 65.15 mg/L, respectively. 2) The target compounds have obvious selectivity, and their anti-oomycete activity is significantly better than their anti-fungal activity. 3) Interestingly, there are significant differences in the structure-activity relationship of different substituents or the same substituent at different positions anti-oomycete and anti-fungal against P. capsici and F. graminearum, respectively. The study provides an idea for further exploring the bioactivities of 28-acyloxyoleanolic acid derivatives, and develops the application of 28-acyloxyoleanolic acid derivatives containing anhydride in agriculture.

Design, Synthesis, and Anticancer Activity of Novel Enmein-Type Diterpenoid Derivatives Targeting the PI3K/Akt/mTOR Signaling Pathway.

The enmein-type diterpenoids are a class of anticancer ent-Kaurane diterpnoids that have received much attention in recent years. Herein, a novel 1,14-epoxy enmein-type diterpenoid 4, was reported in this project for the first time. A series of novel enmein-type diterpenoid derivatives were also synthesized and tested for anticancer activities. Among all the derivatives, compound 7h exhibited the most significant inhibitory effect against A549 cells (IC50 = 2.16 µM), being 11.03-folds better than its parental compound 4. Additionally, 7h exhibited relatively weak anti-proliferative activity (IC50 > 100 µM) against human normal L-02 cells, suggesting that it had excellent anti-proliferative selectivity for cancer cells. Mechanism studies suggested that 7h induced G0/G1 arrest and apoptosis in A549 cells by inhibiting the PI3K/AKT/mTOR pathway. This process was associated with elevated intracellular ROS levels and collapsed MMP. In summary, these data identified 7h as a promising lead compound that warrants further investigation of its anticancer properties.

Investigating the superconducting state of 2H−NbS2 as seen by the vortex lattice

2H−NbS2 is a classic example of an anisotropic multiband superconductor, with significant recent work focusing on the interesting responses seen when high magnetic fields are applied precisely parallel to the hexagonal niobium planes. It is often contrasted with its sister compound 2H−NbSe2 because they have similar onset temperatures for superconductivity, but 2H−NbS2 has no charge density wave whereas in 2H−NbSe2 the charge density wave order couples strongly to the superconductivity. Using small-angle neutron scattering, a bulk-sensitive probe, we have studied the vortex lattice and how it responds to the underlying superconducting anisotropy. This is done by controlling the orientation of the field with respect to the Nb planes. The superconducting anisotropy, Γac=7.07±0.2, is found to be field independent over the range measured (0.15 to 1.25 T), and the magnetic field distribution as a function of the applied magnetic field is found to be in excellent quantitative agreement with anisotropic London theory modified with a core-size cutoff correction, providing the first complete validation of this model. We find values of λab=141.9±1.5 nm for the in-plane London penetration depth, and λc∼1µm for the out-of-plane response. The field-independence indicates that we are primarily sampling the larger of the two gaps generating the superconductivity in this material. Published by the American Physical Society 2024

Design, synthesis, biological evaluation and in silico study of N-(Pyrimidin-2-yl)alkyl/arylamide derivatives as quorum sensing inhibitors against Pseudomonas aeruginosa.

The emergence of bacterial resistance to antimicrobial agents poses a serious threat to the effectiveness of treating bacterial illnesses. A major factor contributing to antimicrobial resistance is biofilm formation, driven by quorum sensing (QS). QS suppression inhibits the QS signaling pathway, obstructing cell-to-cell communication. This study focuses on N-(pyrimidin-2-yl)alkyl/arylamide derivatives, which were designed, synthesized, and characterized for their QS inhibitory effects. Among the synthesized compounds (3a-j), compounds 3b, 3d, and 3h exhibited the highest QS inhibitory activity, with inhibition zones of 17.66 ± 6.17, 14.00 ± 6.24, and 17.33 ± 0.66mm, respectively. Further, molecular docking studies revealed binding affinities between -8.4 and -6.3kcal/mol, indicating strong interactions with the target proteins. Moreover, molecular dynamic simulations confirmed the stability of the protein-ligand complexes for compounds 3b and 3h. Additionally, in-silico methods were employed to predict the physicochemical properties of these molecules. Overall, these findings underscore the potential of N-(pyrimidin-2-yl)alkyl/arylamide derivatives as QS inhibitors, offering a new perspective for developing alternative antimicrobial therapies.

Design, synthesis and biological evaluation of amphiphilic benzopyran derivatives as potent antibacterial agents against multidrug-resistant bacteria

Antimicrobial resistance has emerged as a significant threat to global public health. To develop novel, high efficiency antibacterial alternatives to combat multidrug-resistant bacteria, A total of thirty-two novel amphiphilic benzopyran derivatives by mimicking the structure and function of antimicrobial peptides were designed and synthesized. Among them, the most promising compounds 4h and 17e displayed excellent antibacterial activity against Gram-positive bacteria (MICs = 1–4 μg/mL) with weak hemolytic activity and good membrane selectivity. Additionally, compounds 4h and 17e had rapid bactericidal properties, low resistance frequency, good plasma stability, and strong capabilities of inhibiting and eliminating bacterial biofilms. Mechanistic studies revealed that compounds 4h and 17e could effectively disrupt the integrity of bacterial cell membranes, and accompanied by an increase in intracellular reactive oxygen species and the leakage of proteins and DNA, ultimately leading to bacterial death. Notably, compound 4h exhibited comparable in vivo antibacterial potency in a mouse septicemia model infected by Staphylococcus aureus ATCC43300, as compared to vancomycin. These findings indicated that 4h might be a promising antibacterial candidate to combat antimicrobial resistance.

An efficient and simple approach for synthesizing indazole compounds using palladium-catalyzed Suzuki-Miyaura cross-coupling.

A series of indazole derivatives (6a-6i and 7a-7i) has been synthesized using Suzuki Miyaura cross-coupling with a palladium catalyst from readily available starting materials. An efficient and reliable methodology was employed for the synthesis, and the compounds were thoroughly characterized using 1H NMR, 13C NMR, FT-IR, and HRMS analysis to confirm their structural integrity and purity. Density function theory (DFT) computation identified four compounds (6g, 6h, 7g, and 7h) with significant energy band gaps. Additionally, the molecular electrostatic potential study highlighted the distinct electrical characteristics of these indazole molecules. Subsequent molecular docking investigations were carried out using the AUTODOCK method with two separate protein data bank (PDB) structures (6FEW, 4WA9) involved in renal cancer pathways. The results showed that eight substances PDB: 6FEW (6g, 6h, 7g, and 7h) and PDB: 4WA9 (6a, 6c, and 7c, 7g) had the highest binding energies, indicating their potential as therapeutic agents for treating kidney cancer.

Convergent synthesis, kinetics and computational attributions of indole-N-phenyltriazole hybrids bearing N-(aryl)butanamides as alkaline phosphatase inhibitors

In the research delineate herein, an innovative sequence of new series of multi-functional target molecules (9a-i) having indole-N-phenyltriazole bi-heterocyclic hybrids unified with N-arylated butanamides was synthesized as alkaline phosphatase inhibitor. The structural validation of all the formulated compounds was accomplished through IR, EI-MS, 1H NMR, 13C NMR and CHN analysis data. The in vitro enzyme inhibitory investigation revealed the efficacy of these bi-heterocyclic derivatives, 9a–i, as potent inhibitors of alkaline phosphatase relative to the standard used. The compound 9h was found to be the most active compound (IC50 = 0.062 ± 0.017 μM), and its inhibitory activity is about 10 times higher than potassium dihydrogen phosphate (KH2PO4) (IC50 = 5.251 ± 0.468 μM). The kinetics mechanism was attributed by evaluating the Lineweaver–Burk plots, which revealed that compound 9h inhibited the alkaline phosphatase non-competitively to form an enzyme–inhibitor complex. The inhibition constant Ki determined from Dixon plots for this compound was 0.045 μM. The computational study was in full agreement with the experimental records and these ligands exhibited good interactions and binding energy values. These molecules also demonstrated mild cytotoxicity toward red blood cell membranes when analyzed through hemolysis. So, based on the presented results, these molecules, being the promising inhibitors of alkaline phosphatase, might be deliberated as suitable medicinal scaffolds to render normal calcification of bones and teeth.

Synthesis, characterization and thrombolytic activity evaluation of novel pyrazolo[3,4-b]pyridine-4-carbohydrazide derivatives

Thrombosis, a leading cause of numerous fatalities, particularly in developed nations, accounts for thousands of deaths. The contemporary lifestyle inevitably leads to occurrences of venous thrombosis, including deep vein thrombosis and thromboembolism. This article presents a groundbreaking study where a novel series of N′-(arylmethylidene)-6-(p-methoxyphenyl)-3-methyl-1-phenyl-1H-pyrazolo[3,4-b] pyridine-4-carbohydrazide derivatives were efficiently synthesized and screened for thrombolytic activities. Compounds 4a, 4c, 4d, and 4h demonstrated the best antiplatelet activities when using different agonists such as arachidonic acid and collagen. These compounds showed >50 % activity by using agonist collagen and inhibited >50 % platelet aggregation in whole human blood. Compounds 4c and 4d showed the greatest inhibitory effect of 97.98 % and 98.97 %, respectively as compared to other synthesized compounds and aspirin. For platelet aggregation using arachidonic acid, all the synthesized compounds 4a, 4c, 4d and 4h shown >93 % inhibition than that of aspirin. In computational studies, ligands 4c(ap) and 4d(ap) exhibited potent interaction with the COX-1 active site, suggesting inhibitory potential against thrombolytic activities. Ligand 4c(ap) scored 8896 and ACE of -418.31 kcal/mol, while 4d(ap) scored 8742 and ACE of -417.43 kcal/mol. Similarly, ligands 4c(ap) and 4h(ap) displayed outstanding docking scores at the COX-2 active site, with 4c(ap) scoring 8574 (ACE:301.49 kcal/mol) and 4h(ap) scoring 8424 (ACE:276.16 kcal/mol). Synthesized compounds particularly 4c and 4d have the potential to be used for clinical trials and could be beneficial for the designing and development of novel therapeutics for cardiovascular and thromboembolic ailments.

Multicomponent reaction for the synthesis of novel nicotinonitrile analogues bearing imidazole or triazole moieties: Synthesis, antioxidant activity, molecular docking, and ADMET studies

The study is aimed to synthesize, characterize and evaluate antioxidant activity of novel highly functionalized nicotinonitrile analogues bearing imidazole or triazole moieties. The targeted compounds were synthesized via one-pot four component reaction and characterized by elemental and spectrometric analyses. The newly 16-synthesized compounds were assessed as antioxidant agents using the total antioxidant capacity assay. The experimental results indicated that four out of sixteen compounds exhibited the most antioxidant effect with 38.81 and 18.66 mg AAE/g considering ascorbic acid equivalent. The molecular docking screening on the novel potential compounds, further supported by ADMET/drug-likeness screening was conducted. The outcomes of the docking simulations revealed that compounds 4e, 4f, 4g, and 6h are considered safe and non-toxic. These 4 compounds exhibited significant affinity, as evidenced by binding energies of -11.9, -10.9, -11.2, and -11.60 kcal/mol, respectively, with the active site of human cytochrome P450. Additionally, these compounds showed significant binding energies with NAD(P)H Oxidase of -9.90, -9.50, -9.90, and -9.50 kcal/mol, respectively. These interactions involved diverse types of molecular interactions and demonstrated favorable binding energies, indicating the potential of these compounds to modulate antioxidant enzymes and demonstrate promising antioxidant effects. The in-silico ADMET profiles of compounds 4e, 4f, 4g, and 6h indicated their adherence to the Lipinski rules, subsequently, they could be potential orally bioavailable drug-like molecules.

Plant natural product-based pesticides in crop protection: semi-synthesis, mono-crystal structures and agrochemical activities of osthole ester derivatives, and study of their toxicology against Tetranychus cinnabarinus (Boisduval).

Owing to large amounts of synthetic pesticides being extensively and unreasonably used for crop protection, currently, resistance and negative impacts on human health and environment safety have appeared. Therefore, development of potential pesticide candidates is highly urgent. Herein, a series of ester derivatives of osthole were designed and synthesized as pesticidal agents. Six spatial configurations of 4'-(p-toluenoyloxy)osthole (4b), 4'-(m-fluorobenzoyloxy)osthole (4f), 4'-(p-fluorophenylacetyloxy)osthole (4m), 4'-(3'',4''-methylenedioxybenzoyloxy)osthole (4q), 4'-formyloxyosthole (4u) and 4'-acetyloxyosthole (4v) were determined by X-ray mono-crystal diffraction. Compounds 4b, 4'-(p-chlorobenzoyloxy)osthole (4g), 4'-(m-chlorobenzoyloxy)osthole (4h), 4'-(p-bromobenzoyloxy)osthole (4i) and 4'-(2''-chloropyridin-3''-ylcarbonyloxy)osthole (4p) showed higher insecticidal activity than toosendanin against Mythimna separata Walker; notably, compound 4b displayed 1.8 times insecticidal activity of the precursor osthole. Against Tetranychus cinnabarinus Boisduval, compounds 4g and 4h showed 3.3 and 2.6 times acaricidal activity of osthole, and good control effects in the glasshouse. Scanning electron microscopy assay demonstrated that compound 4g can damage the cuticle layer of T. cinnabarinus resulting in death. Compounds 4g and 4h can be further studied as lead pesticidal agents for the management of M. separata and T. cinnabarinus. These results will pave the way for application of osthole derivatives as agrochemicals. © 2024 Society of Chemical Industry.

Development of Xanthoangelol-Derived Compounds with Membrane-Disrupting Effects against Gram-Positive Bacteria.

Infections caused by multidrug-resistant pathogens have emerged as a serious threat to public health. To develop new antibacterial agents to combat such drug-resistant bacteria, a class of novel amphiphilic xanthoangelol-derived compounds were designed and synthesized by mimicking the structure and function of antimicrobial peptides (AMPs). Among them, compound 9h displayed excellent antimicrobial activity against the Gram-positive strains tested (MICs = 0.5-2 μg/mL), comparable to vancomycin, and with low hemolytic toxicity and good membrane selectivity. Additionally, compound 9h demonstrated rapid bactericidal effects, low resistance frequency, low cytotoxicity, and good plasma stability. Mechanistic studies further revealed that compound 9h had good membrane-targeting ability and was able to destroy the integrity of bacterial cell membranes, causing an increase in intracellular ROS and the leakage of DNA and proteins, thus accelerating bacterial death. These results make 9h a promising antimicrobial candidate to combat bacterial infection.

A New Class of Benzo[b]thiophene-chalcones as Cholinesterase Inhibitors: Synthesis, Biological Evaluation, Molecular Docking and ADME Studies.

In this study, heterocyclic compounds containing a benzothiophene scaffold were designed and synthetized, and their inhibitory activity against cholinesterases (ChE) and the viability of SH-SY5Y cells have been evaluated. Benzothiophenes 4a-4i and benzothiophene-chalcone hybrids 5a-5i were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), revealing interesting structure-activity relationships. In general, benzothiophene-chalcone hybrids from series 5 proved to be better inhibitors of both enzymes, with compound 5f being the best AChE inhibitor (IC50 = 62.10 μM) and compound 5h being the best BChE inhibitor (IC50 = 24.35 μM), the last one having an IC50 similar to that of galantamine (IC50 = 28.08 μM), the reference compound. The in silico ADME profile of the compounds was also studied. Molecular docking calculations were carried out to analyze the best binding scores and to elucidate enzyme-inhibitors' interactions.