Synthesis, evaluation and molecular docking studies of cycloalkyl/aryl-3,4,5-trimethylgallates as potent non-ulcerogenic and gastroprotective anti-inflammatory agents

Supplementary Information

Table S1 Free energies of binding [ΔGbind (kcal/mol)] of test compoundsand their hydrogen bonding interactions with various amino acids involved in the binding site of COX-1 (PDB ID:3KK6) and COX-2 (PDB ID:1CX2) isoenzymes

Compound / Hydrogen bonds between atoms of compounds and
amino acids of COX-1 / ΔGbind (kcal/mol) / Hydrogen bonds between atoms of compounds and
amino acids of COX-2 / ΔGbind (kcal/mol)
Atom of compound / Amino acid / Distance (Å) / Atom of compound / Amino acid / Distance (Å)
4a / OCH3 of acidic moiety
OCH3 of acidic moiety
OH of phenolic moiety
OH of phenolic moiety / OH Tyr385
OH Ser530
NH Gln192
NH Ile517 / 1.531
1.526
1.827
1.989 / -57.79 / OCH3 of acidic ring
OCH3 of acidic moiety
OH of phenolic moiety
C=O of ester / NH2 Arg120
OH Tyr355
OH Tyr385
NH Ser353 / 2.093
2.203
1.850
1.994 / -61.20
4b / OCH3 of acidic moiety
OCH3 of acidic moiety
O of ester / NH2 Arg120
OH Tyr355
NH Gly526 / 2.381
1.793
3.359 / -68 / OCH3 of acidic moiety
OCH3 of acidic moiety
OCH3 of phenolic moiety
OCH3 of phenolic moiety / NH2 Arg120
OH Tyr355
OH Ser530
OH Tyr385 / 1.713
1.465
1.987
2.446 / -70.44
4c / OCH3 of ring A
OCH3 of acidic moiety / NH2 Arg120
OH Ser530 / 1.59
3.5 / -49.45 / OCH3 of acidic moiety
OCH3 of acidic moiety
OCH3 of phenolic moiety
OCH3 of phenolic moiety / OH Ser530
OH Tyr385
NH2 Arg120
OH Tyr355 / 2.8
3.327
3.043
1.844 / -51.71
4d / OCH3 of acidic moiety
C=O of ester / OH Tyr355
OH Ser530 / 2.046
2.959 / -37.51 / OCH3 of acidic moiety
OCH3 of acidic moiety / OH Tyr385
OH Ser530 / 1.945
3.618 / -57.46
4e / OCH3 of acidic moiety
OCH3 of acidic moiety
C=O of Aldehyde / NH2 Arg120
OH Tyr355
OH Tyr385 / 1.622
2.169
3.674 / -50.46 / OCH3 of phenolic moiety
C=O of Aldehyde / OH Tyr355
NH2 Arg120 / 3.433
2.098 / -58.28
4f / OCH3 of acidic moiety
OCH3 of acidic moiety
C=O of ester / NH2 Arg120
OH Tyr355
OH Ser530 / 3.482
1.709
3.483 / -31.81 / OCH3 of acidic moiety
OCH3 of acidic moiety / NH2 Arg120
OH Tyr355 / 1.988
1.995 / -51.43
4g / OCH3 of acidic moiety
OCH3 of acidic moiety
OCH2O of phenolic moiety / NH2 Arg120
OH Tyr355
OH Tyr385 / 2.076
1.979
2.449 / -53.42 / OCH3 of acidic moiety
OCH3 of acidic moiety
OCH2O of phenolic moiety / NH2 Arg120
OH Tyr355
OH Ser530 / 2.566
1.864
1.896 / -58.43
4h / OCH3 of acidic moiety
C=O of phenolic moiety
O of lactone ring / OH Ser530
OH Ser516
NH His90 / 2.536
1.806
1.726 / -56.89 / OCH3 of acidic moiety
OCH3 of acidic moiety
OCH3 of acidic moiety / NH2 Arg120
OH Tyr355
NH2 Arg513 / 2.493
2.527
2.468 / -46.31
4i / OCH3 of acidic moiety
OCH3 of acidic moiety
C=O of ester / NH2 Arg120
OH Tyr355
OH of Ser530 / 3.963
2.086
3.378 / -24.54 / OCH3 of acidic moiety
OCH3 of acidic moiety / NH2 Arg120
OH Tyr355 / 2.127
2.099 / -12.54

Fig. S1 The electrostatic (Coulomb) interaction energy (in kcal/mol) between indomethacin, celecoxib, SC-558, 4b, 4d and each single amino acid involved in ligand recognition obtained after docking simulations inside the binding site COX-2 receptor

Fig. S2 The vdW interaction energy (in kcal/mol) between indomethacin, celecoxib, SC-558,4b, 4d and each amino acid residue involved in ligand recognition obtained after docking simulations inside the binding site COX-2 receptor

Fig. S3The electrostatic interaction (Coulomb) energy (in kcal/mol) between indomethacin, celecoxib, SC-558, 4b, 4d and each single amino acid involved in ligand recognition obtained after docking simulations inside the binding site COX-1 receptor

Fig. S4 The vdW interaction energy (in kcal/mol) between indomethacin, celecoxib, Sc-558, 4b, 4d and each amino acid residue involved in ligand recognition obtained after docking simulations inside the binding site COX-1 receptor

Fig. S5 Correlation between calculated logP and predicted logP values of test compounds

Fig. S6 Correlation between calculated logS and predicted logS values of test compounds