Design, synthesis, 2D-QSAR, molecular dynamic simulation, and biological evaluation of topiramate–phenolic acid conjugates as PPARγ inhibitors

Future Journal of Pharmaceutical Sciences

Table 6 Binding affinities and interactions of TPAC with amino acid residues

Conjugates	Binding energies (Kcal/mol)	Interactions with amino acids
Conjugates	Binding energies (Kcal/mol)	Hydrogen bonds	Hydrophobic interactions
T1	− 9.0	ARG288, GLU343	SER342, ILE281, LEU330, CYS285, ARG288
T2	− 10.84	SER289, CYS285	HIS449, TYR327, LEU469, HIS323, ARG288, ALA292, ILE326, LEU330, ILE281, LEU336, MET364
T3	− 11.27	ARG288, CYS285, MET364, PHE360	MET329, ILE326, LEU330, LEU333, TYR327, CYS285
T4	− 11.14	ARG288, CYS285, PHE360, PHE363	MET329, ILE326, LEU330, LEU333, TYR327, CYS285, ARG288, LEU356, PHE363, MET364, ILE281, LEU353
T5	− 9.34	SER342, LEU340	LEU255, ARG280, ILE281, MET348, CYS285, GLY284, ARG288, VAL339, ILE341, PHE264
T6	− 9.13	ARG288, GLY284, GLU343	ILE341, MET348, LEU330, ILE281, CYS285, ARG288
T7	− 10.56	ARG288, CYS285, PHE360	ALA292, MET329, ILE326, LEU330, LEU333, TYR327, ILE281, LEU353, MET364, CYS285
T8	− 10.36	ARG288, CYS285, PHE360	ALA292, MET364, ILE326, LEU330, LEU333, TYR327, LYS367, ILE281, LEU353, MET364, CYS285
T9	− 9.37	ARG288, GLU343	MET364, ILE326, LEU330, LEU353, PHE287
T10	− 10.40	CYS285, PHE360, PHE363	ILE326, MET329, LEU330, LEU333, ARG288, TYR327, MET364, CYS285, LYS367, ILE281, LEU353
TPM	− 6.9	ARG280	CYS285, ARG288, PHE264, PHE287, LEU330, VAL339, LEU340, MET364
CF	− 6.1	CYS285	ARG288, SER289, ALA292, ILE326, MET329, LEU330, LEU333
GW9662	− 9.0	ARG288, ILE326, TYR327	CYS285, SER289, ALA292, ILE296, HIS323, MET329, LEU330, LEU333, MET364, LYS367, HIS449