Abstract:
Rheumatoid arthritis is the chronic autoimmune disease which affects the entire body. We analyzed three compound classes, including Benzoic acid derivatives, Cinnamic acid derivatives, and flavonoids, to predict their drug-like features. Computational analysis using Molinspiration tool, SWISS ADME and pKCsm tools, showed that cinnamic acid and benzoic acid derivatives had good oral absorption, but flavonoids had poor oral absorption, as indicated by literature. Absorption levels of compounds are measured using several parameters, including P-glycoprotein substrate or inhibitors, Caco-2 permeability, skin permeability, and intestinal absorption in humans. A Papp coefficient of >8 × 10-6 and values >0.90 indicate high Caco-2 permeability and easy uptake. All compounds, except flavonoids had less Caco-2 permeability. Values 90%). Most values for log Kp (> -2.5) indicate high permeation through the skin. Nearly all other tested molecules complied with Lipinski's rule and bioavailability criteria in SWISS ADME. Docking was performed to determine the binding affinities between the drugs and receptors. Amongst flavonoid compounds, rutin showed the most significant interaction, with diverse hydrogen bonding with amino acids Tyr340, Asp450, Tyr451, Lys294, Lys221, Arg194, Gln220, and Val342. Gallic acid also showed strong interaction with the receptor, with participation of amino acids Ser343, Val342, Trp213, Arg194, and Arg217. Finally, ferulic acid presented the best docking results, with maximum interaction with amino acids Arg435, Thr190, and Arg458. It was concluded that tested polyphenolic compounds have interesting anti arthritic activities and the tested compounds can be processed for further analysis.
Page(s):
60-60
DOI:
DOI not available
Published:
Journal: Abstract Book on International Conference on Life Sciences (ICLS-23) 11-12 May 22-23, Volume: 0, Issue: 0, Year: 2023
Keywords:
Bioavailability
,
molecular docking
,
Dug likeness
,
Active pocket
,
Blood brain Barrier