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

Bulletin of the National Research Centre

Table 12 Predicted ADMET properties of some selected arylimidamide-azole derivatives and the newly designed analogues

Comp ID	A					D		M				E	T
	HIA	P-glycoprotein			Skin	BBB	CNS	CYP-2D6		CYP3A4		TCE	AMES	MRTD
	%	S	I	II	LogKp	LogBB	LogPS	S	I	S	I	TCE	AMES	MRTD
Six (6) arylimidamide-azole hybrids with the highest pIC₅₀
21	92.56	YES	YES	YES	− 2.74	− 0.62	− 2.36	NO	YES	YES	YES	0.843	YES	0.276
22	90.83	YES	YES	YES	− 2.74	− 0.62	− 2.31	NO	YES	YES	YES	0.906	NO	0.193
26	90.68	YES	YES	YES	− 2.74	− 0.55	− 2.27	NO	YES	YES	YES	0.939	YES	0.282
31	92.52	YES	YES	YES	− 2.74	− 1.13	− 2.45	NO	NO	YES	YES	0.904	YES	0.406
33	90.80	YES	YES	YES	− 2.74	− 1.16	− 2.40	NO	YES	YES	YES	0.997	YES	0.323
36	100.0	YES	YES	YES	− 2.74	− 0.70	− 2.29	NO	YES	YES	YES	0.848	NO	0.132
Newly designed arylimidamide-azole analogs
36a	100	YES	YES	YES	− 2.74	− 0.66	− 1.92	NO	YES	YES	YES	0.437	NO	0.073
36b	100	YES	YES	YES	− 2.74	− 0.70	− 2.13	NO	YES	YES	YES	0.529	NO	0.088
36c	100	YES	YES	YES	− 2.74	− 0.63	− 1.80	NO	YES	YES	YES	0.354	NO	0.072
36d	100	YES	YES	YES	− 2.74	− 0.60	− 1.74	NO	YES	YES	YES	0.144	NO	0.068
36e	100	YES	YES	YES	− 2.74	− 0.42	− 1.47	NO	NO	YES	YES	0.237	NO	0.098
36f	100	YES	YES	YES	− 2.74	− 0.61	− 1.44	NO	NO	YES	YES	0.290	NO	0.112
36 g	100	YES	YES	YES	− 2.74	− 0.55	− 1.26	NO	NO	YES	YES	0.338	NO	0.123

BBB—Blood–brain barrier, CNS—central nervous system, HIA—human intestinal absorption, Skin—skin permeability, LogBB—the logarithmic ratio of brain to plasma drug concentration, LogPS—blood–brain permeability-surface area product, CYP-34A—cytochrome p450 isoform, CYP-2D6—cytochrome p450 isoform, S—substrate, I—inhibitor, MRTD—maximum recommended tolerated dose, TCE—total clearance