Light-activated targeted degradation of VHL drug for selective tumor killing: A novel strategy for precision therapy of bladder cancer.

Cocrystals of telmisartan with ascorbic acid: Enhanced solubility and antiviral potency against Japanese encephalitis virus.

Salinomycin inhibits orthopoxvirus infection in vitro and in vivo by blocking endosomal acidification.

From pain relief to proliferation arrest: Synthesis and biological evaluation of novel diclofenac-tethered Schiff bases as VEGFR-2 inhibitors and apoptosis inducers, guided by in silico molecular docking and ADME profiling.

Hepatitis B virus ribonuclease H inhibitors: Coming of age?

Phenoxy-linked colchicine derivatives: A structure-based approach toward enhanced selectivity and α-tubulin interaction.

Discovery of 2-(methylamino)-5,6,7,8-tetrahydropyrido[4,3-d] pyrimidine derivatives as novel HsClpP activators for multiple myeloma therapy.

Lilium lancifolium bulbs are edible-medicinal resources rich in polysaccharides, proteins, polyphenols, and saponins, but fresh bulbs are prone to browning, nutrient loss, and microbial contamination. Blanching combined with drying is a key postharvest strategy for maintaining quality. This study evaluated steam and hot-water blanching followed by hot-air drying to determine their effects on color, polyphenols, antioxidant activity, and cytotoxicity. Blanching markedly reduced browning, with steam for 15 min and hot water for 2 min showing the best color protection. Treatments enhanced polyphenol retention, reducing losses of regaloside A and promoting accumulation of regaloside E. Antioxidant capacity was highest after 6 min of hot-water blanching, while 10 min of steam blanching produced the strongest antiproliferative effect with good selectivity (selectivity index = 5.08). Multi-criteria decision analysis identified hot-water blanching for 6 min (B6-D) as optimal and steam blanching for 10 min (S10-D) as secondary. Blanching-drying synergy effectively improved color stability, preserved key phenolics, and enhanced bioactivity in L. lancifolium bulbs. Hot-water blanching for 6 min followed by drying is recommended as the optimal method, providing a scientific basis for high-quality processing and functional product development. © 2026 Society of Chemical Industry.

Equivalence of the Peripheral Common Trunk and Adrenal Central Vein in Left Adrenal Vein Sampling.

Organometallic gold(III) (C^S)-cyclometallated complexes as candidates to new drugs against chagas disease.

Drug resistance in non-small cell lung cancer (NSCLC), frequently driven by EGFR mutations and compensatory bypass signaling via ACK1 and c-Met, remains a critical clinical challenge. Consequently, the design of multi-targeted agents capable of dual EGFR/ACK1 inhibition with c-Met activity represents a rational strategy to overcome these resistance mechanisms. Based on this hypothesis, a novel series of fused pyridopyrimidopyrimidine derivatives was designed and synthesized. The structures of the target compounds were confirmed using elemental analysis and spectral methods (IR, NMR, MS). The anticancer potential of the synthesized compounds was evaluated against a panel of solid tumor cell lines, with a focus on drug-resistant phenotypes. Among these, compound 11b and its analogue 7g demonstrated the strongest activity in drug-resistant H1975 cells, showing IC₅₀ values of 0.42 μM and 0.85 μM, respectively, and favorable selectivity indices. Mechanistic assays confirmed that 11b effectively suppressed the phosphorylation of EGFR, ACK1, and c-Met kinases. Furthermore, flow cytometric analysis indicated the induction of apoptosis, characterized by Annexin-V binding and Caspase-3 activation, alongside cell cycle modulation. Computational ADME-toxicity prediction indicated drug-like properties and low predicted toxicity risks. These findings position compound 11b , and to a lesser extent 7g , as strong candidates for further optimization as multitargeted kinase inhibitors against resistant forms of non-small-cell lung cancer. N-substituted and Fused different pyridopyrimidopyrimidines systems.

Trypanosoma cruzi and Leishmania spp. are the protozoan parasites responsible for Chagas disease and leishmaniasis. The treatment of these neglected diseases relies on repurposed drugs and faces several challenges including high toxicity, and the emergence of resistant strain. Therefore, there is a constant demand for promising antiparasitic agents. The present work aimed to investigate seventeen prepared N1,N4-bisbenzylbutane-1,4-diamines against recombinant T. cruzi and L. infantum as well as their inhibitory effects against the T. cruzi recombinant trypanothione reductase (TcTR). N1,N4-bis(4-chlorobenzyl)butane-1,4-diamine showed significant trypanocidal activity with an IC50 of 6.0±0.9μM with a selectivity index of 4.3. This compound was more active than the positive control, benznidazole (IC50 of 14.6). It moderately inhibited TcTR with an IC50 of 55.6±18.6μM. N1,N4-bis(4-chlorobenzyl)butane-1,4-diamine also inhibited L. infantum with an IC50 of 19.3±1.2μM (SI of 3.4). N1,N4-bis((E)-3-(2-methoxyphenyl)allyl)butane-1,4-diamine exhibited potent inhibitory effect against T. cruzi (2.4±0.3μM); However, it also turned out to be highly cytotoxic to the L929 fibroblast cell line. Its inhibitory effect against TcTR was also significant, with an IC50 of 3.9±1.9μM. Alongside the two diamines, nine other synthesized derivatives displayed antitrypanosomal activity with IC50 ranging from 8 to 150μM. Concerning the leishmanicidal effects, all tested compounds were moderately active. Moreover, during in silico studies of the active compounds using TcTR (PDB ID 4NEW), N1,N4-bis((E)-3-(2-methoxyphenyl)allyl)butane-1,4-diamine emerged as the most promising candidate, displaying both strong binding affinity and significant biological activity.

Discovery of mangiferin lipophilic amide derivatives as novel fatty acid synthase inhibitors with potent anti-hepatocellular carcinoma activity.

Neuronal cancers, including glioblastoma and neuroblastoma, remain highly aggressive malignancies with limited therapeutic success, thereby necessitating the identification of novel agents with improved selectivity and safety profiles. The present study aimed to evaluate the in vitro anticancer potential of neferine, a bisbenzylisoquinoline alkaloid isolated from Nelumbo nucifera, against neuronal cancer cell lines. Neferine was extracted and purified using acid–base partitioning followed by flash column chromatography. Its cytotoxic activity was assessed against N2a (mouse neuroblastoma) and U-87 MG (human glioblastoma) cell lines, along with NHA (normal human astrocytes), using the MTT assay. Neferine exhibited a concentration-dependent reduction in cell viability across all tested cell lines. The IC₅₀ values were determined to be 26.2 µg/mL for N2a and 34.8 µg/mL for U-87 MG cells, indicating moderate cytotoxic potency. Importantly, a significantly higher IC₅₀ value of 73.2 µg/mL was observed in normal astrocytes, demonstrating reduced toxicity toward non-cancerous cells. The selectivity index (SI) values of 2.79 (N2a) and 2.10 (U-87 MG) further confirmed the preferential cytotoxicity of neferine toward cancer cells. In comparison, the reference drug cisplatin showed higher cytotoxic potency but lower selectivity, indicating greater toxicity to normal cells. Overall, the findings suggest that neferine possesses promising anticancer activity with a favorable selectivity profile, highlighting its potential as a lead compound for the development of safer therapeutic strategies against neuronal cancers.

Feline infectious peritonitis virus (FIPV) poses a significant threat to cats worldwide. Besides the limited development of antiviral drugs that mainly target virus proteins, concerns about resistance to mutant strains - similar to those seen in human and other mammalian viruses - remain high. Therefore, addressing these challenges involves developing innovative antiviral therapies, such as host-directed treatments that target host cell processes essential for viral replication. FIPV infection induced distinctive dynamics of lipid droplet (LD) remodelling, characterized by an increase in LD abundance from early to mid-infection, followed by a subsequent decline. Phosphorylated hormone-sensitive lipase, a key mediator of LD hydrolysis and fatty-acid release, became activated after the mid-infection phase, potentially contributing to elevated intracellular fatty-acid availability during late infection. Notably, atglistatin (DABPU-DM) and its derivatives robustly suppressed FIPV replication in Crandell-Rees feline kidney (CRFK) and feline macrophage Fcwf-4 cells, coincident with preservation of LD integrity and inhibition of LD breakdown. Among these compounds, DABPU-DE had the best selectivity index (686.0±35.2) against FIPV, with a higher half-maximal cytotoxic concentration (274.4±3.6 µM) and a lower half-maximal inhibitory concentration (0.4±0.02 µM). Moreover, combining DABPU-DE (0.18 µM) with remdesivir (1.35 µM), a viral RNA-dependent RNA polymerase inhibitor, showed a very strong synergistic effect (CI=0.09 and Bliss synergy score=14.46±1.80) in inhibiting FIPV replication in CRFK cells, even at lower doses than either drug alone. In conclusion, DABPU-DE is a promising antiviral candidate for FIPV, and its synergistic effect with remdesivir warrants further research in cats infected with FIPV.

Purpose: To evaluate the In vitro antiplasmodial, cytotoxic and antioxidant activities of Chrysophyllum albidum (African star apple) kernel extracts, with emphasis on their potential as dual-function antimalarial agents. Methods: Ethanol, aqueous and essential oil extracts of C. albidum kernels were prepared using standard extraction procedures. Antiplasmodial activity was assessed against Plasmodium falciparum 3D7 (chloroquine-sensitive) and Dd2 (chloroquine-resistant) strains using a lactate dehydrogenase (LDH) fluorescence assay at concentrations of 1.56–25 µg/mL, with chloroquine and artemisinin as reference drugs and resistance index was dertermined. Cytotoxicity was evaluated on RAW 264.7 macrophage cells at 62.5–1000 µg/mL using a resazurin-based assay to determine CC50 and selectivity index (SI). Antioxidant activity was determined using DPPH (1–30 µg/mL), nitric oxide and hydrogen peroxide (10–100 µg/mL) scavenging assays. IC50 values were calculated by nonlinear regression analysis. Results: Ethanol and essential oil extracts exhibited notable antiplasmodial activity (IC50 : 4.08–5.50 µg/mL) against both parasite strains, with slightly higher efficacy against the 3D7 strain compared to Dd2. The aqueous extract showed comparatively higher IC50 values, indicating lower potency. All extracts demonstrated low cytotoxicity (CC50 > 479 µg/mL) and high selectivity indices (SI > 10), suggesting preferential toxicity towards the parasite. Resistance indices (≤ 1.5) indicated minimal cross-resistance with standard drugs. The extracts also showed strong antioxidant activity across all assays, with IC50 values ranging from 33 to 46 µg/mL, and were most effective in DPPH radical scavenging, comparable to ascorbic acid. Conclusion: These findings support the traditional use of C. albidum kernel extracts as potential sources of antiplasmodial and antioxidant agents, warranting further isolation of active compounds.

The co-evolution of multidrug resistance amongst oral pathogens and sub-par treatment outcomes associated with traditional OSCC therapy calls for alternative strategies, which not only differ in terms of the underlying mechanism but should also be biocompatible. One such strategy entails nanoparticle synthesis utilizing plant extracts as both reducing agents and ligands; secondary metabolic compounds endow the produced nanomaterials with unique biological activity. The aim of the present review is a comprehensive analysis of the preparation, characterization, and dual antibacterial/antitumorigenic activities of AgNPs, CuNPs, and FeNPs produced from aqueous extracts of Azadirachta indica and Syzygium cumini. The nucleation, growth kinetics, size distribution, and particle charge are all governed by the polyphenols content of aqueous plant extract; in particular, Syzygium cumini nanoparticles display monodispersity and low particle sizes (<20 nm) in comparison to larger Azadirachta indica nanoparticles that show enhanced stability due to the abundant presence of terpenoids. Amongst oral biofilm-forming bacteria, AgNPs have shown the greatest breadth of antimicrobial action at the minimum concentration range of 5-25 μg/mL; AgNPs showed greater than 90% biofilm inhibition whereas CuNPs showed antifungal efficacy against Candida albicans. FeNPs, though inherently less cytotoxic, offer a magnetically responsive platform for targeted drug delivery and localized hyperthermia. In OSCC cell lines, biogenic nanoparticles induced dose-dependent apoptosis through mitochondrial membrane depolarization, upregulation of the Bax/Bcl-2 ratio, cytochrome c release, and caspase-3 activation, with selectivity indices consistently superior to chemically synthesized counterparts — attributed to the modulation of oxidative thresholds by surface-adsorbed phytochemicals. Taken together, these phytometallic nanocomplexes represent a mechanistically integrated dual-action platform with potential translational relevance to precision oral therapeutics.

Self-assembling nano-antimicrobial peptides (nano-AMPs) hold significant promise for addressing bacterial resistance, yet the persistent activity-biocompatibility paradox remains a major scientific challenge. Here, we present an "integrated offense‒defense" strategy in which binding to mammalian cells is inhibited (defense) but bacterial membrane insertion is improved (offense), effectively decoupling antimicrobial potency from host cytotoxicity. We demonstrated that nano-AMPs with moderate surface potentials (∼+20mV) preferentially bind to bacteria and exhibit minimal interactions with mammalian cells because of the inherent charge disparity between bacterial and mammalian cell membranes. Experimental and theoretical analysis revealed that systematic sequence engineering resulted in peptide nanofibers with loose molecular packing and high exposure of hydrophobic residues. The optimized nano-AMP exhibited potent antimicrobial activity (MIC of 5∼6 µM) and exceptional biosafety (therapeutic index TI = HC10 / MIC > 30; selectivity index SI = IC20 / MIC> 50). A murine skin wound infection model confirmed the antimicrobial efficacy of this peptide, which reduced the bacterial burden and promoted wound healing.

Conventional targeted protein degradation (TPD) strategies operate by hijacking intracellular proteolytic machinery, limiting their therapeutic scope. Here, we present protein-radical-oxidation targeting enediyne chimera (PROTEC), a TPD platform that can be located exclusively outside of host cells and degrades pathogen proteins via a radical-based oxidative mechanism. The maleimide-fused enediyne core undergoes cycloaromatization under physiological conditions to generate reactive radical species. Strategic incorporation of sulfate-based hydrophilicity-adjusting groups (HAGs) restricts PROTEC activity to the extracellular space, enhancing biosafety. Using a ligand (spc14) that targets the conserved free fatty acid binding pocket, we demonstrate that PROTECs effectively degrade the coronavirus spike protein and potently inhibit seasonal coronaviruses. Further optimization through a propargyl ester moiety and increased sulfation yielded PROTEC-d, a lead compound with a half-maximal inhibitory concentration of 0.22 µM and a selectivity index exceeding 3000. Our findings establish PROTEC as a safe and versatile strategy for the extracellular degradation of pathogen proteins, with promising potential for broad-spectrum antiviral applications.

The first comprehensive study of a series of seven mesoionic tetrazolylidene gold(I) chloride complexes (1-7) featuring a range of alkyl and aryl substituents (Me, t-Bu, iPr, Ph, Tol, Dipp, Mes) is reported. Three synthetic pathways enabling access to scarcely explored abnormal 1,3-disubstituted tetrazolium ligand precursors (L1-L7) have been established. All complexes are characterized by NMR spectroscopy, mass spectrometry, and elemental analysis, confirming their composition and purity. Single-crystal X-ray crystallography of six gold(I) complexes (1-6) reveals nearly linear coordination (176.49(11)-179.0(2)°) at the gold(I) center and a distinct geometric arrangement across the series. NMR stability studies with model nucleophiles L-cysteine (Cys) and glutathione (GSH) support the structural findings, demonstrating rapid and complete reaction of complexes 1-7 with thiols, as confirmed by 1H NMR and ESI-MS. The antiproliferative activity of the obtained complexes (1-7) and selected precursors (L2, L3, L5, L7) has been evaluated using MTT assays against human A2780 (ovarian) and A549 (lung) cancer cell lines, alongside noncancerous VERO E6 kidney cells for comparison. Most of the complexes display high selectivity indices (SIA2780 = 63.2-86.7) and potent antiproliferative effects in the low submicromolar range against A2780, outperforming cisplatin and matching the activity of auranofin. Overall, the results presented here demonstrate the potential of gold(I) tetrazolylidene-based complexes for medicinal applications.