Structure Activity Relationship of 4-((2-hydroxybenzylidene) amino) benzoic acid and 4-((4 methoxybenzylidene) amino) benzoic acid as Potential Larvicidal Agents against Aedes aegypti Larvae
2026· Journal of Applied Sciences and Environmental Management· Vol 30, pp. 2066-2073· 0 citations
TL;DR
Findings indicate that these Schiff bases have promising larvicidal activity, suggesting their potential as safer and more environmentally friendly pest management alternatives, and highlight the possibility of these compounds supporting environmental biodiversity.
Abstract
The widespread application of conventional synthetic pesticides has raised major environmental issues because of their persistence, bioaccumulation, and biomagnification. The urgent need to address these risks calls for the development of more eco-friendly alternatives in pest management. Consequently, the objective of this paper was to investigate the structure activity relationship of 4-((2-hydroxybenzylidene) amino) benzoic acid [A1] and 4-((4 methoxybenzylidene) amino) benzoic acid [A2] as potential larvicidal agents against Aedes aegypti larvae using appropriate standard procedures. Data obtained reveals that percentage mortality was determined using Abbott's formula. Both compounds demonstrated larvicidal activity in a dose-dependent manner. At 2.5 mg/mL, the Schiff bases achieved 95.5 and 99 % mortality for A1 and A2 respectively. At lower concentrations of 0.5 mg/ml, the ligands showed slightly high activity. These findings indicate that these Schiff bases have promising larvicidal activity, suggesting their potential as safer and more environmentally friendly pest management alternatives. The results highlight the possibility of these compounds supporting environmental biodiversity.
In this study of antiplasmodium activity of ethyl 4-oxocyclohexane-1-carboxylate-based 1,2,4,5-tetraoxane analogs containing aromatic and alicyclic moieties, tetraoxanes were synthesized using a non-metallic approach in two steps from ethyl 4-oxocyclohexane-1-carboxylate, aromatic aldehydes, and ketones; the yields of 1,2,4,5-tetraoxane analogs varied from 29% to 54%. The newly synthesized tetraoxanes were evaluated for their in vitro antiplasmodium activity against chloroquine-sensitive (3D7) strains of Plasmodium falciparum. The compounds exhibited antiplasmodial activity ranging from 43.41 nM to 7.89 nM. Two tetraoxanes (3 and 4) had comparable antiplasmodial activity with artemisinin (5.97 nM), which was taken as a standard drug. The cytotoxicity (CC50) of the tested compounds was not detectable. The ligand binding mechanism was further corroborated using the molecular docking analysis on the most active compound, i.e., 2k, from the series of tetraoxanes having an aromatic moiety, and compounds 3 and 4 from the series of tetraoxanes having an alicyclic moiety with the active site of Plasmodium cysteine protease falcipain-2 enzyme. Among them, compound 2k showed a docking score of −4.36 kcal mol−1, and artemisinin portrayed a score of −4.46 kcal mol−1. Evidence suggests that synthesized compounds derived from tetraoxanes exhibit antiplasmodial activity, and further biological validation may be required to advance their potential for malaria treatment.
A library of 4-aminoquinoline derivatives and benzoxaborole-4-aminoquinoline hybrids, linked through amide and 1H-1,2,3-triazole spacers, was synthesized and evaluated against both chloroquine-sensitive (3D7) and -resistant (W2) strains of Plasmodium falciparum. Structure–activity relationship studies revealed that antiplasmodial potency was strongly influenced by the length of the alkyl chain and by the nature of the terminal functional group (azido, aldehyde, or benzyl alcohol). Notably, incorporation of the benzoxaborole core significantly enhanced activity relative to the parent 4-aminoquinoline derivatives. Among the series, hybrid 8b emerged as the most potent analogue, displaying superior activity against the CQ-resistant W2 strain compared with the reference antimalarials quinine and chloroquine. The hybrids exhibited negligible cytotoxicity toward HEK-293 cells, affording selectivity indices of up to ∼700. UV-visible spectroscopic titrations demonstrated that compound 8b binds monomeric heme more selectively than CQ at both physiological and digestive vacuole pH, supporting inhibition of hemozoin formation as its primary mode of action. Furthermore, homology modelling, induced-fit docking, and molecular dynamics simulations with both wild-type and benzoxaborole-resistant (H36Y/D470N) PfCPSF3 suggested that the scaffold can maintain a stable Zn2+-coordinated binding mode in both protein variants. These findings indicate a potential dual mechanism involving hemozoin inhibition and PfCPSF3 targeting, warranting further experimental validation.
Anuradha Saini, Sumit Kumar, B. Pradines et al.· RSC Advances· 0 citations
Chagas disease (CD), once found mainly in underdeveloped countries, is becoming a public health problem in the developed world. Although the drug benznidazole (BZN) is effective in the acute phase of the disease, it causes toxicity due to the formation of reactive substances resulting from presystemic metabolism, which have the ability to bind to DNA structures. This study conducts experimental tests with the epimastigote and trypomastigote species of the parasite, followed by drug–target interaction analyses through molecular docking against the enzymes trypanothione reductase, cruzain, and TcGAPDH, as well as pharmacokinetic prediction based on MPO analyses. In vitro tests revealed CPN4F’s significant efficacy in reducing host cell viability and inhibiting parasite growth. Molecular docking indicated CPN4F’s favorable energy ordering and superiority to BZN against the cruzain target (ΔG < −6.0 kcal mol–1), while molecular dynamics simulations showed that the complex remains stable in the 500 ns range. Pharmacokinetic estimates suggested high cell permeability (P app > 10 × 10–6 cm/s) but potential metabolic stability concerns (CLint,u > 8 mL/min/kg), showing good oral bioavailability, although with moderate metabolism. The CPN4F molecule demonstrates potent in vitro efficacy against Chagas disease, outperforming BZN in molecular docking studies targeting cruzain. Despite concerns about metabolic stability due to its high cell permeability and lipophilic nature, CPN4F exhibits low acute oral toxicity, highlighting its potential as a safe and effective treatment option.
J. Pinto, Francisco Nithael Melo Lucio, L. R. Ribeiro et al.· ACS Omega· 0 citations
Succinate dehydrogenase (SDH) inhibitors face cross-resistance issues due to similar structures. To address this problem, we designed heterocyclic carboxamide derivatives based on a 3,5-dichloro-2,6-difluoropyridin-4-amine scaffold. Compounds A1 and A2 showed excellent antifungal activity against Rhizoctonia solani (EC50 = 1.08 and 1.18 mg/L), outperforming boscalid (EC50 = 1.82 mg/L). They also exhibited broad-spectrum activity against four pathogenic fungi. In vivo rice leaf tests confirmed good protective effects (A1 and A2 at 92.88% and 89.35%, respectively). Mechanistic studies revealed that A1 and A2 disrupt mycelial morphology (Scanning electron microscopy analysis and transmission electron microscopy analysis) and inhibit SDH, supported by molecular docking and enzyme activity assays. Importantly, acute oral toxicity to bees was low (LC50 > 500 mg/L), comparable to commercial fungicides. These results identify A1 and A2 as promising, bee-safe leads for next-generation SDHI fungicides.
Boyi Sun, Hui Wang, Dandan Wang et al.· Journal of Agricultural and...· 0 citations
Findings suggested that compound 6m might be a potent candidate as a succinate dehydrogenase inhibitor (SDHI) against R. solani with strong protective and curative effects even at 50 μg/mL.
Bo Luo, Yanbing Wu, Qingsi Zhang et al.· Journal of Agricultural and...· 0 citations
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.
E. El‐Helw, Mahmoud Kamal, Eslam M. Hosni et al.· Bioorganic chemistry (Print)· 0 citations