Design, Synthesis, Characterization, Toxicological Effects, and Molecular Docking Insights of Some Novel Quinoline Compounds as Potential Insecticides

Design, Synthesis, and Exploration of Biological Activities of Novel Benzoxazole Derivatives through In-silico and In vivo Approaches.

INTRODUCTION Many natural and synthetic compounds have been investigated for their anti-inflammatory and analgesic properties, but most of them possess significant adverse effects. The versatility of benzoxazole derivatives allows for the design of compounds with specific target interactions. Structural modifications may lead to the development of more efficacious and safer drugs for various medical conditions. METHOD A series of substituted benzoxazole compounds was synthesized, yielding six (E)-1-[4-{2- (benzo[d]oxazol-2-yl)phenylamino}phenyl]-3-(substituted phenyl)prop-2-en-1-ones, denoted as 3a-3f, and further characterized by IR, NMR, and mass spectroscopic methods. The synthesized derivatives were tested for anti-inflammatory and analgesic activities using animal models. The binding interactions of the synthetic compounds with the targets were investigated through a molecular docking study using Schrodinger Maestro version 2022-4. Molecular dynamics (MD) simulation was performed for 50 ns to investigate the protein's characteristics, monitor internal molecular transformations, and assess the long-term stability of the protein-ligand complex. RESULTS All the compounds exhibited significant anti-inflammatory and analgesic activities at a dose of 100 mg/kg compared to Diclofenac. In in silico studies, the compounds exhibited the required binding interactions and stability. DISCUSSION The docking studies indicated that the compound substituted with 3-hydroxyphenyl (3c) behaved as a COX-1 inhibitor. The simulated complexes of 3c with COX-1 and COX-2 demonstrated stability throughout the simulation, with RMSD values of 3.5 Å and 4 Å, respectively. CONCLUSION The present research would pave the way for researchers to synthesize more benzoxazole derivatives devoid of significant adverse effects using novel approaches.

Synthesis, Characterization, Molecular Docking, and In Silico ADMET Analysis of Newly Bioactive Pyrazolophosphonate and Spiro-Pyrazole Derivatives

This study presents an efficient and simple method for synthesizing novel bioactive organophosphorus compounds 4 and 5 via a three-component condensation reaction of aminophenylpyrazolinone, an aromatic aldehyde, and triethyl phosphite, using L-proline as the organocatalyst. Furthermore, a series of spiro-pyrazolone derivatives was successfully obtained by a simple condensation reaction between aminophenylpyrazolinone and various aromatic aldehydes. In addition, molecular docking studies demonstrated that all compounds effectively interact with the target protein's active site, forming stable ligand–protein complexes. ADMET analysis against E. coli also reveals favorable pharmacokinetic properties for most compounds. However, compounds 6a, 6g, and 7j show potential toxicity, which may limit their applicability as drugs. 3-amino-1-phenyl-2-pyrazolin-5-one, aromatic aldehydes, and triethyl phosphite were used in condensation reactions and Kabachnik–Fields/Pudovik-type reactions to create the compounds. HRMS and NMR (1H, 13C, 2D) were used for characterization. Pharmacokinetic characteristics were predicted using pKCSM, and binding affinities were evaluated using molecular docking with the E. coli protein 1FJ4. The produced compounds showed stable docking conformations and strong binding affinities (-7.0 to -9.2 kcal/mol). The compounds with the best interaction profiles were 6d, 6e, 6f, and 7i. Compounds 6a, 6g, and 7j showed potential toxicity, but ADMET analysis indicated good intestinal absorption and acceptable metabolism. The synthetic method worked well and did not harm the environment. Several derivatives show promising pharmacological potential, as indicated by docking and ADMET results. This study introduces a simple synthesis of biologically active pyrazolophosphonate and spiro-pyrazole derivatives with promising antibacterial and pharmacokinetic profiles, highlighting compounds 6d, 6e, 6f, and 7i as potential drug candidates.

Design, Synthesis, In Vitro Cytotoxicity, and Molecular Docking of Novel 2-Thioxoimidazolidin-4-one Derivatives

Synthesis, Biological Evaluation, and in Silico Studies of Novel Triazole- and Oxadiazole-Based Acetamides as Urease and α-Glucosidase Inhibitors.

This study investigated the therapeutic potential of novel 1,2,4-triazole- and 1,3,4-oxadiazole-based acetamide derivatives as dual-target inhibitors of urease and α-glucosidase, two enzymes implicated in gastrointestinal disorders and type 2 diabetes, respectively. An integrated approach combining multistep organic synthesis, in vitro biological evaluation, molecular docking, in silico ADME prediction, and density functional theory (DFT) analysis was employed to identify potent lead compounds with favorable pharmacokinetic properties. Starting from benzoic acid, a series of 1,2,4-triazole derivatives (8a-c) and 1,3,4-oxadiazole derivatives (9d-f) bearing substituted acetamide moieties were successfully synthesized. All compounds exhibited inhibitory activity against both target enzymes. Compound 8c was the most potent urease inhibitor (IC₅₀ = 6.14 ± 1.06 µM), while compound 9e showed the strongest α-glucosidase inhibition (IC₅₀ = 27.29 ± 0.41 µM), surpassing the reference inhibitor acarbose (IC₅₀ = 38.25 ± 0.12 µM). Computational analyses supported the experimental findings: ADME predictions indicated favorable drug-like properties, and molecular docking demonstrated strong binding interactions, with compound 8a exhibiting the highest affinity for α-glucosidase (-7.165 kcal/mol) and compound 9e showing the strongest binding to urease (-7.30 kcal/mol). DFT calculations further correlated biological activity with electronic properties, revealing relatively small HOMO-LUMO energy gaps for the most active compounds, 8c (0.14831 a.u.) and 9e (0.14302 a.u.). Collectively, these findings identify compounds 8c and 9e as promising lead scaffolds for the development of next-generation inhibitors of urease and α-glucosidase.

Thienopyrimidine–piperazine hybrids as multifunctional pharmacophores: design, synthesis, and biological evaluation

Abstract A series of novel 5,6-dimethylthieno[2,3-d]pyrimidine-piperazine hybrids was rationally designed, synthesized, and evaluated to explore their potential as multifunctional bioactive agents. The target compounds were synthesized via nucleophilic substitution of 4-chloro-5,6-dimethylthieno[2,3-d]pyrimidine with structurally diverse substituted piperazines, affording the desired derivatives in good yields. Structural confirmation was achieved through elemental analysis and comprehensive spectroscopic techniques, which were consistent with the proposed molecular frameworks. Derivatives 4h and 4i showed the most potent antimicrobial activity, while 4f and 4g exhibited superior antioxidant effects. Compounds 4g, 4j, and 4k demonstrated comparatively higher anti-inflammatory activity. Structure–activity relationship (SAR) analysis revealed that electron-withdrawing groups enhance antimicrobial activity, whereas aromatic and electron-rich substituents favor antioxidant and anti-inflammatory responses. Although the activity was lower than that of standard drugs, several compounds displayed meaningful biological potential. These results suggest that the thienopyrimidine–piperazine scaffold is a promising framework for the development of multifunctional therapeutic agents. GRAPHICAL ABSTRACTDiagram of Thienopyrimidine-Piperazine core linked to antibacterial, antifungal, anti-inflammatory, and antioxidant activities with icons.The diagram showcases a central Thienopyrimidine-Piperazine core structure, with arrows pointing to four activity categories: Antibacterial (depicted by Gram-positive and Gram-negative icons), Antifungal (featuring Candida and Aspergillus), Anti-inflammatory (illustrating protein denaturation and COX inhibition), and Antioxidant (showcasing DPPH radical scavenging and OPPH). It includes sections for "Efficient Synthesis & Characterization" and "Broad Spectrum Biological Activities." The overall title emphasizes the multifunctional potential of these hybrids as antimicrobial, antioxidant, and anti-inflammatory agents.

Potential c-Met-targeted pyrazole-pyridine-oxadiazole hybrids: synthesis, anticancer activity, and computational rationale.

A novel series of pyrazole-pyridine-1,3,4-oxadiazole hybrid derivatives (10a-m) was designed, synthesized, and characterized by IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. The multi-step route proceeded via nucleophilic aromatic substitution, cyclocondensation, oxidative aromatization, and S-alkylation, affording target compounds in good to excellent yields (88-93%). Derivatives were screened for anticancer activity against A549 (lung) and MCF-7 (breast) cell lines using Foretinib as reference. Compound 10d (2,4-di-OCH3) was most potent, with IC50 values of 0.29 ± 0.15 μM (A549) and 3.1 ± 0.5 μM (MCF-7), comparable to, or numerically better than, Foretinib (IC50 = 0.49 ± 0.026 μM, A549); no formal statistical comparison was performed. SAR analysis showed electron-donating substituents, especially methoxy groups, enhanced potency. Compounds 10c, 10d, and 10h were markedly less cytotoxic toward non-cancerous NIH/3T3 fibroblasts (IC50 = 138.41, 66.36, and 95.03 μM) than toward the cancer lines, indicating a favorable selectivity margin. Docking against c-Met (PDB: 3LQ8) showed 10d had the highest binding affinity (-5.54 kcal mol-1), forming hydrogen-bond and π-cation interactions with ASP 1222 and ARG 1203, consistent with c-Met as a plausible target, though direct biochemical confirmation is needed. DFT calculations (B3LYP/6-311++G(d,p)) for 10c, 10d, and 10h confirmed that 10d has the smallest HOMO-LUMO gap (3.74 eV) and highest chemical softness, consistent with its superior activity. Collectively, these findings identify 10d as a promising scaffold for further optimization and biological evaluation.