Although inflammation triggers immune-mediated healing and repair, chronic inflammation can result in several diseases. Cyclooxygenase (COX) enzymes are inhibited by NSAIDs, which are used to relieve the symptoms of inflammation. Meclofenamic and Zileuton are examples of dual COX/LOX inhibitors that provide improved stomach protection and safer cardiovascular characteristics. This study was aimed to develop anti-inflammatory medications with improved safety profiles by presenting novel flufenamate conjugates that combine 5-LOX inhibitor efficacy with COX inhibition. The COX-1 inhibition of compounds 14 and 15 was higher than that of Celecoxib (IC50 = 77.4 µM), with an IC50 range of 15-26 µM. Compounds 14 and 16 showed the best selectivity indices (ratio between IC50 of COX-1 and COX-2), which were 5.01 and 5.86 µM, respectively. Conjugates 14 and 16 displayed excellent COX-2 inhibiting activity, with IC50 values of 5.0 -17.6 µM. Outstanding 5-LOX inhibition was demonstrated by all conjugates, with IC50 values varying between 0.6 and 8.5 µM. In RAW 264.7 cells, compounds 14 and 15 significantly decreased PGE2 levels to a range of 61-89 pg/mL in contrast to Celecoxib (119.9 pg/mL). Compounds 14 and 17 showed exceptional NO scavenging action, with IC50 values of 0.238 × 106 and 0.289 × 106 µM, respectively. mTOR levels dramatically diminished for all conjugates. Conjugates 14 and 17 markedly raised levels nrf2. Molecular docking studies were used to validate the findings of this investigation.
© 2025. The Author(s).

This study integrates bioinformatics and experimental approaches to characterize bioactive peptides derived from quinoa 11S-globulin (Chenopodium quinoa Willd) hydrolyzedin silico by stem bromelain (EC3.4.22.32). A total of 109 peptides were generated, of which 14 sequences with more than five amino acids were selected based on molecular docking and dynamics simulations against key metabolic targets (ACE-I, DPP-IV, α-glucosidase, and lipoxygenase). NIYQIS and QDQHQKIR demonstrated the highest binding affinities and hydrogen-bonding interactions, with ADMET predictions confirming their non-toxic and bioavailable profiles. In vitro, NIYQIS showed the strongest inhibitory activity against ACE-I (53%), DPP-IV (16.36%) and exhibited the highest antioxidant capacity (ORAC: 0.75 μM TE/μM peptide). Conversely, QDQHQKIR demonstrated the highest α-amylase inhibition (18.43%) and Cu2+ chelation (40.4%), supporting its role in carbohydrate metabolism and metal-ion homeostasis. Overall, NIYQIS emerged as the most promising peptide, highlighting the potential of quinoa-derived peptides as functional ingredients to mitigate oxidative stress and metabolic disorders.

Resveratrol was subjected to a diversity-oriented synthesis using oxidative transformations by various biorelevant, biomimetic, or biomimetic-related chemical reagents. Using a combined strategy of ultrahigh-resolution profiling, bioactivity screening, and bioactivity-guided isolation, 19 metabolites were obtained. The compounds were tested for their in vitro enzyme inhibitory activity on angiotensin-1 converting enzyme (ACE), cyclooxygenase-1 and -2, and 15-lipoxygenase (LOX), and evaluated for their relevant drug-like properties in silico. The compounds demonstrated a generally increased cardiovascular protective and anti-inflammatory potential and better drug-likeness compared to resveratrol. Trans-δ-viniferin (6) was identified as a competitive, C-domain-selective ACE inhibitor that is over 20 times more potent than resveratrol. Further, trans-ε-viniferin (2) acted as an over 40 times stronger LOX inhibitor than resveratrol. While our results cannot be directly translated to the health benefits of dietary resveratrol consumption without further studies, it is demonstrated that biologically relevant oxidative environments transform resveratrol into potent cardiovascular protective and anti-inflammatory metabolites.

Corallocarpus glomeruliflorus (CGP), a plant native to Yemen, has been traditionally used for the management of various health conditions, including cancer, inflammation, and diabetes. This study presents the first comprehensive phytochemical and pharmacological investigation of CGP, revealing novel molecular mechanisms and therapeutic potential. Phytochemical analysis of the CGP extract revealed the presence of diverse bioactive compounds, including phenols, flavonoids, and other secondary metabolites. Notably, this is the first report identifying maritimetin, assafoetidin, kaempferol 3-rhamnoside 7-xyloside, and lespenefril in CGP, compounds with significant therapeutic potential. The total phenolic content was 88.12 ± 4.48 mg GAE/g, significantly higher than previously reported for related species (63.78 ± 1.27 mg GAE/g), and the total flavonoid content was 22.1 ± 0.01 mg QE/g. The extract demonstrated superior antimicrobial activity against Pseudomonas aeruginosa compared to previous studies, with a zone of inhibition of 16.7 ± 1.53 mm at 200 mg/mL concentration. The CGP extract displayed strong antioxidant activity in DPPH, FRAP, and phosphomolybdenum assays, with an IC50 value of 48.39 ± 1.58 μg/mL in the DPPH assay, compared to 9.88 ± 0.54 μg/mL for the positive control ascorbic acid. Most significantly, the CGP extract exhibited more potent selective anticancer effects on human breast (MCF-7) and colon (HCT-116) cancer cell lines than previously reported for related Cucurbitaceae species, with IC50 values of 49.18 ± 2.81 μg/mL and 244.2 ± 9.86 μg/mL, respectively. Our novel molecular docking studies revealed previously unreported interactions between CGP compounds and key therapeutic targets, particularly Pim-1, PIK3CA, α-amylase, and Gyr-B, providing new insights into its mechanism of action.
© 2025 The Authors.

A series of 2-(4-bromobenzyl) tethered 4-amino aryl/alkyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines (7a-7u) were designed, synthesized, characterized and screened against a panel of cancer cell lines. Compound 7a, in particular, emerged as a potent antiproliferative agent against FaDu cells (HTB-43) with an IC50 value of 1.73 μM. 7a induced morphological alterations in FaDu cells were observed via brightfield microscopy and DAPI staining, confirming cytotoxicity. Autophagy and apoptotic effects of 7a were confirmed by acridine orange staining, Rhodamine 123 staining, and western blot analysis, which revealed dose-dependent increases in LC3A/B and cleaved caspase-3 levels, respectively. Further, 7a impaired cell migration and colony formation, as demonstrated by scratch and clonogenic assays. Additionally, 7a reduced oxidative stress and induced G2/M phase cell cycle arrest in MCF-7 cells. 7a emerged as a dual topoisomerase I and II inhibitor, and results were supported by molecular docking and simulation studies. In anti-inflammatory studies, 7a exhibited selective inhibition of COX-2 over COX-1, supporting its dual anticancer and anti-inflammatory properties.
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