Table 4.

Molecular docking of 1,3,6-trihydroxy-4,5,7-trichloroxanthone (TTX) against some receptors involved in doxorubicin resistance.

Protein signaling	Protein Data Bank ID	Root median square deviation	Free energy of binding			Hydrogen bond
			Native ligand	TTX	Difference	Native ligand	TTX
Raf-1	3OMV	1.3823	−83.22	−79.37	3.85	Cys424	Cys424, Lys431, Ser427, Gly426
NIK	5T8O	1.6348	−107.13	−69.95	37.18	Glu442, Glu472, Leu474, Phe537	Leu474 (2)
c-JNK	3PZE	1.2523	−75.91	−75.42	0.49	Met111 (2), Glu109	Met111, Glu109, Ser34 (2)
CDK2	2UZO	0.9929	−80.93	−68.47	12.46	His84, Asp86, Asp145, Asn132	Leu83, Asp145, Lys33
Survivin	2QFA	1.7134	−59.85	−46.89	12.96	Arg18 (3), Phe93, Glu40	Arg18, Val89
CDK6	5L2I	1.6338	−107.04	−71.89	35.15	Glu18, Val101	Val101, Asp102, Asp104
p38 MAPK	4TYH	1.6099	−92.61	−72.15	20.46	Lys53, Met109	Gly33, Lys53, Met109
Btk	3GEN	0.9364	−80.78	−68.38	12.4	Thr474, Glu475, Met477	Leu408
Akt	3MV5	0.9403	−83.18	−56.66	26.52	Glu434, Ala230	Leu156
MMP-1	966C	1.0760	−88.55	−63.35	25.2	Glu219, Ala182, Asn180, Leu181	Gly179, His228, His218
Bcl-2	4C5D	1.7437	−126.44	−61.43	65.01	–	–

Protein Data Bank ID were obtained from PDB Database (RCSB, USA).

The boldface types in Raf-1 and c-JNK represented the smallest differences free energy of binding of TTX to that of the native ligands.

The number in parentheses represented the number of hydrogen bonds which were formed by each amino acid.

NIK = nuclear factor kappa B (NFκB)-inducing kinase, c-JNK = c-Jun N- 42 terminal kinase, Btk = Bruton tyrosine kinase, Akt = Ak mouse thymoma, CDK = cyclin-dependent kinases, MAPK = mitogen-activated protein kinase, MMP = matrix metalloproteinase, Bcl = B cell lymphoma.