Aug 2026· Bioorganic chemistry (Print)· Vol 181, pp.
110407
· 0 citations· 54 references
Medicine
TL;DR
Biochemical evaluation of triazinone 3 revealed significant reductions in acetylcholinesterase activity and in total protein, carbohydrate, and lipid contents compared with untreated larvae, indicating that larval mortality was accompanied by cholinergic disturbance and depletion of metabolic reserves.
Abstract
A new series of benzo[h]quinoline-based heterocyclic derivatives was synthesized and evaluated as larvicidal candidates against third instar Culex pipiens larvae. The prepared compounds showed concentration-dependent toxicity with clear structure-related variation across the series. Benzo[h]quinolone-triazinone hybrid 3 was the most active derivative, giving the lowest LC50 value (142 ± 0.2 μg/mL) and the highest toxicity index (100), and was approximately 2.1-fold more potent than chlorpyrifos under the same assay conditions. Biochemical evaluation of triazinone 3 revealed significant reductions in acetylcholinesterase activity and in total protein, carbohydrate, and lipid contents compared with untreated larvae, indicating that larval mortality was accompanied by cholinergic disturbance and depletion of metabolic reserves. Molecular docking was performed for all synthesized compounds against acetylcholinesterase (AChE) and nicotinic acetylcholine receptor (nAChR), whereas molecular dynamics simulations were applied to the bioassay-selected compound 3 and the reference systems to examine the dynamic behavior of the predicted complexes. Triazinone 3 maintained a stable AChE complex during simulation and showed persistent contacts with residues including SER250, TRP212, HIS567, PHE416, THR252, TYR258, SER327, and PHE457. In the nAChR model, the trajectory was more mobile but retained recurrent contacts involving ASP153, ASN196, SER149, LYS198, TYR200, TYR152, LYS156, and TYR94. SwissADME analysis further suggested that the activity profile was influenced by a balance between target-recognition potential and physicochemical accessibility. Overall, the findings identify benzo[h]quinoline-based heterocycles, particularly triazinone 3, as promising larvicidal scaffolds and support further optimization of this class as potential alternatives to conventional insecticides.
In the pursuit of novel insecticidal agents, a series of new thieno[2,3-b]quinoline derivatives were synthesized via efficient and versatile routes, starting from ethyl 3-aminothieno[2,3-b]quinoline-2-carboxylate. The synthesized compounds including hydrazone (8a–c), arylidene (9a–c), and pyrano[3,2-c]thieno[2,3-b]quinoline (10a–c) derivatives were characterized using FT-IR, NMR, and mass spectrometry. Their insecticidal efficacy was evaluated against both nymph and adult stages of Aphis fabae, with median lethal concentration (LC50) values determined through probit analysis. Compound 10b exhibited the highest potency, with LC50 values of 0.117 mg/L (nymphs) and 0.366 mg/L (adults), approaching the activity of the commercial insecticide acetamiprid. Molecular docking studies against the Aplysia californica acetylcholine-binding protein (AChBP, PDB: 3SQ6), a surrogate for insect nicotinic acetylcholine receptors, revealed strong binding affinities for the pyranothienoquinoline derivatives, particularly 10b (−7.30 kcal/mol), supported by multiple hydrogen bonds and hydrophobic interactions with key residues. These findings underscore the potential of the pyrano[3,2-c]thieno[2,3-b]quinoline scaffold as a promising candidate for the development of new, target-specific insecticides.
Mokhtar A Abdul-Malik, A. K. Kamal El‐dean, Abdel Haleem M. Hussein et al.· ACS Omega· 0 citations
Natural products from fungi are a significant source for drug discovery. This study investigates six previously uncharacterized metabolites isolated from the poisonous mushroom Tricholoma pardinum using an integrated in silico approach to evaluate their therapeutic potential. Pharmacokinetic (ADMET) profiling predicted varied drug-likeness and toxicity profiles, with several compounds showing potential to cross the blood-brain barrier. Molecular docking and MM-GBSA calculations identified compound 1 as a potent inhibitor of Poly [ADP-ribose] polymerase 1 (PARP1), with a strong binding affinity (XP GScore: -6.756; ΔGbind: -48.75 kcal/mol). This interaction is anchored by a robust network of hydrogen bonds with key residues, including ASP914, CYS908, and THR866. Similarly, compound 6 emerged as a strong binder to Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (PIP4K2γ) (XP GScore: -7.705; ΔGbind: -45.94 kcal/mol), with its binding stabilized by extensive hydrophobic interactions complemented by a critical hydrogen bond with the residue Methionine 206 (MET206). Subsequent 100 ns molecular dynamics simulations confirmed the high stability of both protein-ligand complexes, validating the persistence of these key interactions. These computational findings highlight the potential of metabolites from T. pardinum as novel scaffolds for developing anticancer agents targeting PARP1 and PIP4K2γ, warranting further experimental validation.
A. Amin, H. M. Amin, A. R. Hamad et al.· Technology and Health Care· 0 citations
The increasing resistance of Aedes aegypti L. to conventional larvicides has intensified the search for novel bioactive compounds through molecular design. This study explores the larvicidal efficacy and toxicological profiles of piperine and its saturated analog, tetrahydropiperine, by integrating in silico molecular docking and experimental bioassays. Both compounds were subjected to docking studies using as target enzymes human and insect acetylcholinesterases (PDB: 4EY6 and 6XYU) and the juvenile hormone-binding protein (PDB: 5V13). Tetrahydropiperine exhibited higher binding affinities, with binding energies of -9.36 kcal.mol-1 (4EY6), -9.32 kcal.mol-1 (6XYU), and -10.60 kcal.mol-1 (5V13), compared to piperine, which showed energies of -9.56, -10.83, and -10.49 kcal.mol-1, respectively. In larvicidal bioassays, tetrahydropiperine demonstrated greater activity, with an LC50 of 54.5 μΜ, whereas piperine showed an LC50 of 78.8 μΜ after 24 hours of exposure. Toxicological evaluation in Swiss mice revealed that tetrahydropiperine, at 300 mg.kg-1, caused no significant adverse effects, while piperine induced mortality and behavioral alterations at doses above 50 mg.kg-1. These results suggest that the unsaturation in piperine side chain may act as a toxicophoric moiety, and that its saturation enhances larvicidal selectivity while reducing systemic toxicity. Tetrahydropiperine thus emerges as a promising scaffold for the development of selective, safe, and effective larvicidal agents.
M. S. de Lima Silva, Marcilene S da Silva, Rômulo Carlos Dantas da Cruz et al.· Experimental parasitology· 0 citations
In this study, 30 tetrahydroquinoline-based pyrazole-4-carboxamide derivatives were designed, synthesized, and screened for antifungal activities. Among them, compound 6m displayed the strongest inhibitory activity against Rhizoctonia solani, with a half-maximal effective concentration (EC50) as low as 0.03 μg/mL, superior to Boscalid (EC50 = 0.40 μg/mL) and Fluxapyroxad (EC50 = 0.06 μg/mL). Further detached-leaf assays on rice verified that 6m could markedly suppress the growth of R. solani with strong protective and curative effects even at 50 μg/mL. Follow-up mechanistic studies indicated that compound 6m might exert antifungal activity through SDH inhibition-related mechanisms. These findings suggested that compound 6m might be a potent candidate as a succinate dehydrogenase inhibitor (SDHI) against R. solani. Further research, including field trials and biosafety assessment, was needed to realize the potential of compound 6m as an effective tool for rice protection.
Bo Luo, Yanbing Wu, Qingsi Zhang et al.· Journal of Agricultural and...· 0 citations
The growing crisis of antimicrobial resistance urges the immediate development of new therapeutic pharmaceuticals that can overcome current resistance mechanisms, including biofilm formation. This study included the synthesis and strategic design of a novel set of quinoline-based scaffolds (3-11) to enhance interactions with the bacterial Peptide Deformylase (PDF) enzyme. The compounds underwent extensive in vitro biological assessment, comprising initial inhibition zone (IZ) screening, followed by quantitative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests against a range of Gram-positive, Gram-negative, and fungal strains. The synthesized derivatives exhibited potent, primarily bactericidal activity, with compounds 4, 6, and 10 emerging as notably outstanding candidates. These three compounds exhibited significant activity against S. aureus (MIC = 7.8 μg/mL), demonstrating equivalent potency to the standard reference antibiotic. Additionally, the anti-biofilm efficacy of these leading candidates was assessed against S. aureus and S. typhi at sub-inhibitory doses. Compound 6 emerged as a prominent dual-action drug, demonstrating strong bactericidal activity and significant dose-dependent biofilm destruction. It exhibited considerable biofilm inhibition against both S. aureus (56.76%) and S. typhi (65.93%) even at substantially diluted sub-lethal concentrations (25% MBC). The findings strongly confirm the substituted benzo[h]quinoline core as a highly promising pharmacophore for the development of next-generation antimicrobial medicines effective against both free-floating planktonic cells and tough structured biofilms.
Reham R Raslan, S. Eissa, Moustafa S. Abusaif et al.· Bioorganic chemistry (Print)· 0 citations
4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a vital target for herbicide development. A series of pyrazole-quinoxaline conjugates were designed and synthesized via scaffold hopping and structural optimization. Bioassays revealed that B9 exhibited potent inhibitory activity against Arabidopsis thaliana HPPD (AtHPPD) with an IC50 of 0.11 μM, outperforming mesotrione (0.22 μM) and topramezone (0.48 μM). B18 achieved 100% control over six weeds at 75 g a.i./ha and retained full efficacy against three broadleaf weeds even at 18.75 g a.i./ha. Furthermore, B18 produced less than 20% injury to rice, wheat, cotton, and peanut at 150 g a.i./ha, exhibiting superior crop safety to topramezone (47%-72%). Molecular docking elucidated the binding mechanism of B18 with AtHPPD via Fe2+ coordination, π-π interactions, and hydrogen bonds. Fluorescence titration and microscale thermophoresis assays further confirmed strong binding of B9 and B18 to AtHPPD. This study demonstrated that B18 is a promising, safe, and efficient HPPD-inhibiting herbicide candidate.
Li Liu, Mei Zhang, Lingling Wang et al.· Journal of Agricultural and...· 0 citations