A combined 2-D and 3-D QSAR modeling, molecular docking study, design, and pharmacokinetic profiling of some arylimidamide-azole hybrids as superior L. donovani inhibitors

Ugbe, Fabian Audu; Shallangwa, Gideon Adamu; Uzairu, Adamu; Abdulkadir, Ibrahim

doi:10.1186/s42269-022-00874-1

Bulletin of the National Research Centre

Table 14 Predicted binding interaction profiles of the newly designed molecules with PdxK receptor

From: A combined 2-D and 3-D QSAR modeling, molecular docking study, design, and pharmacokinetic profiling of some arylimidamide-azole hybrids as superior L. donovani inhibitors

ID	Hydrogen bond Interactions			Electrostatic/hydrophobic interactions
ID	Amino acid	Type	Distance (Å)	Electrostatic/hydrophobic interactions
36	THR-229	Conventional	1.95	ASP-124 (π-anion), TYR-85 (π–π stacked), VAL-121 (alkyl), π-alkyl (LEU-43, VAL-41, VAL-19, MET-254, LEU-257) and unfavorable donor–donor clash with SER-47
	GLN-258	Conventional	2.78
	SER-47	Conventional	2.42
	HIS-46	C–H	2.95
	ASP-124	C–H	2.69
	GLY-230	π-donor	3.18
36a	ARG-225	Conventional	2.31	ASP-124 (attractive charge), ASP-124 (π-anion), VAL-121 (alkyl), π-alkyl (LEU-257, LYS-187, ARG-127, TYR-129, VAL-19)
	LYS-187	C–H	2.62
	ASP-124	C –H	2.14
	GLY-228	π –donor	2.32
	GLY-230	π –donor	2.79
36b	HIS-222	Conventional	2.03	ASP-231 (attractive charge), ASP-231 (π-anion), HIS-46 (π–π stacked), VAL-121 (alkyl), π-alkyl (TYR-129, VAL-121, VAL-19, LEU-198, ILE-261)
	HIS-222	C–H	2.35, 2.96
	TYR-129	C–H	3.09
	LYS-187	C–H	2.09
36c	SER-47	Conventional	2.39	π-anion (ASP-124, ASP-125), TYR-85 (π–π stacked), VAL-121 (alkyl), π-alkyl (LEU-43, VAL14, VAL-19, TYR-129, ARG-225)
	ASN-45	C–H	3.00
	THR-227	C–H	2.45
	TYR-226	C–H	1.75
	ARG-225	C–H	2.41
36d	GLY-48	C–H	2.63	ASP-124 (attractive charge), ASP-124 (π-anion), ASP-124 (π-cation), TYR-49 (π–π T-shaped), THR-229 (amide-π stacked), VAL-121 (alky), alkyl (ARG-278, TYR-129, LEU-257, LYS-187) and unfavorable steric bump with THR-229
	GLY-228	π-donor	3.09
	GLY-230	π-donor	2.96
36e	ASP-125	C–H	2.69	ASP-231 (attractive charge), HIS-46 (π-anion), ASP-124 (π-anion), HIS-46 (π–π stacked), VAL-121 (alkyl), π-alkyl (HIS-46, TYR-129, halogen (ASP-231)
	GLY-228	π-donor	3.32
	GLY-230	π-donor	2.83
Pentamidine	SER-47	Conventional	2.52	VAL-19 (π-alkyl) and unfavorable donor-donor clash with SER-12
	THR-229	Conventional	2.53
	TYR-129	C-H	2.36
	GLY-228	π-donor	2.39

ARG—Arginine, ASN—asparagine, ASP—aspartic acid, GLN—glutamine, GLY—glycine, HIS—histidine, LYS—lysine, SER—serine, THR—threonine, TYR—tyrosine

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