DESIGN, SYNTHESIS, AND ANTI-INFLAMMATORY EVALUATION OF QUINOLINE-SCHIFF BASE HYBRIDS: COMPUTATIONAL PREDICTION, COX INHIBITION, AND TNF-α SUPPRESSION STUDIES
DOI:
https://doi.org/10.22159/ijap.2026v18i4.58718Keywords:
Quinoline, Schiff base, Cyclooxygenase, Molecular docking, ADMET, MD simulations, Anti-inflammatory, TNF-αAbstract
Objective: The aim of the study is to design, synthesize, and evaluate novel quinoline-Schiff base hybrids for their anti-inflammatory potential through in silico screening and in vitro assays.
Methods: The study commenced with in silico molecular docking of cyclooxygenase (COX) enzymes (COX-1 and COX-2) and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling. Molecular dynamics (MD) simulation was also performed. This was followed by the synthesis of a series of novel quinoline-Schiff base hybrids and their characterization using analytical methods. Further anti-inflammatory properties were evaluated by in vitro methods such as protein denaturation inhibition assays and tumor necrosis factor-alpha (TNF-α) assays in RAW 264.7 macrophage cell lines.
Results: The designed molecules showed a favorable ADME profile and predicted lower toxicity as per computational analysis. Out of the tested compounds, QSA2 showed the strongest binding affinity toward COX-2 with a docking score of -7.396 kcal/mol and also showed stable interactions in MD simulation. QSA2 and QSC2 exhibited IC₅₀ values of 33.33 and 32.26 µg/mL in the bovine serum albumin (BSA) denaturation assay, and 33.08 and 34.66 µg/mL in the egg albumin denaturation assay, respectively. In the cell viability assay, they preserved over 90% viability in RAW 264.7 cells. In addition, QSA2 showed 27.53% inhibition of LPS-induced TNF-α production.
Conclusion: Among the synthesized Quinoline-Schiff base hybrids, compounds QSA2 and QSC2 have higher binding affinity, pharmacokinetic characteristics, and notable in vitro anti-inflammatory activity. Considering the stable enzyme interaction and superior TNF-α inhibition, the compound QSA2 is the most promising candidate as a lead molecule for further evaluation in preclinical investigations to confirm therapeutic safety and efficacy.
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Copyright (c) 2026 RUTUJA S., DEEPTHI K., MANJUNATH S. KATAGI, JENNIFER FERNANDES, ABDUL FAIROZ AHAMED, SHESHAGIRI DIXIT, KARTHIK G. PUJAR
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