Anti-inflammatory and antioxidant activities of 4-allylpyrocatechol and its derivatives with molecular docking and ADMET investigations

Abnormal production of pro-inflammatory mediators and generation of reactive oxygen species (ROS) play a key role in the development and progression of various human disorders. The study aims to investigate the in vitro anti-inflammatory and antioxidant activity of 4-allyl pyrocatechol (4-APC) and its derivatives (APC-1 and APC-2) by albumin denaturation and 1,1-Diphenyl-2-picrylhydrazyl (DPPH) methods, respectively. Also, the test compounds are studied in silico for their inhibitory potential against the pro-inflammatory and oxidative markers (calpain, FAAH, and TNF-α) via molecular docking. The compounds have exhibited appre- ciable in vitro anti-inflammatory and antioxidant activities. The APC-2 compound has demonstrated significant anti-inflammatory and antioxidant activity (percentage inhibition = 69±0.76 and 77.05±0.92, respectively, at 100 μg/ml) compared to the standard drugs, aspirin and ascorbic acid (percentage inhibition = 82±0.83 and 92.35±0.75, respectively, at 100 μg/ml). The docking study has showed that APC-2 significantly inhibited calpain (PDB ID: 2R9C), FAAH (2WJ1) and TNF-α (2AZ5) inflammatory markers. The drug-likeness, bioactivities, ADME profile (pharmacokinetic) and toxicity properties have also been determined using online tools (Molinspiration, pkCSM, SwissADME, PreADMET). The test compounds have showed accepta- ble drug-likeness, bioactivity score, ADME and toxicity properties. Finally, we conclude that the 4-allylpyrocatechol and its derivatives can be used as lead molecules for their further development as therapeutically useful anti-inflammatory agents