Pyridine-N-Oxide Alkaloids from Allium stipitatum and Their Synthetic Disulfide Analogs as Potential Drug Candidates against Mycobacterium tuberculosis: A Molecular Docking, QSBAR, and ADMET Prediction Approach

Table 2

ADME/Tox predicted values of the disulfide alkaloids.

Cpd ID	Drug-likeness (no. of violations)		Oral bioavailability prediction			Cardiotoxicity prediction	Blood-brain barrier (BBB) penetration			Skin permeability	Protein binding	Primary metabolism	Passive membrane permeability
	Ro5	Ro3	QPlogS	%PHOA	QPPCaco (nm/sec)	QPlogHERG	QPlogBB	CNS	QPPMDCK (nm/sec)	QPlogKp	QPlogKhsa	#metab	Membrane dG insert (kcal/Mol)	Log perm RRCK (cm/s)
A1	0	0	-1.78	100	3034.94	-3.60	0.21	1	4518.15	-1.84	-0.51	1	6.229630	-4.359774
A2	0	0	-2.58	100	3038.80	-4.23	0.15	1	7490.62	-1.64	-0.36	1	5.336709	-4.376275
A3	0	0	-2.83	100	1523.45	-4.60	-0.16	0	1873.12	-1.80	-0.17	3	10.959890	-4.673919
A4	0	0	-2.09	100	8470.62	-3.85	0.59	2	10000	-0.83	-0.27	1	2.591768	-4.204556
A5	0	0	-1.61	100	5091.54	-3.68	0.41	1	8584.47	-1.37	-0.57	2	6.893223	-4.376285
A6	0	0	-3.61	100	8544.57	-4.62	0.59	2	10000	-0.56	0.14	0	4.415087	-4.375935
A7	0	0	-2.73	100	9906.04	-3.89	-0.09	0	10000	-0.64	-0.11	0	-0.264257	-4.094258
A8	0	0	-2.90	100	9906.04	-3.55	0.15	1	10000	-0.83	-0.06	1	1.752616	-4.147198
B9	0	0	-2.71	85	303.06	-5.98	-0.05	1	626.22	-4.03	-0.12	1	4.308330	-4.446987
B10	0	0	-2.86	100	1714.01	-3.86	0.05	1	5095.63	-2.31	-0.29	1	11.416972	-4.640013
B11	0	0	-3.53	100	6345.49	-4.15	0.67	2	10000	-1.15	-0.04	1	2.017210	-4.245295
B12	0	0	-2.09	90	953.75	-3.17	-0.33	0	1135.252	-3.188	-0.45	0	6.398424	-4.404494

QPlogS: predicted aqueous solubility (-6.5-0.5); %PHOA: predicted human oral absorption on 0 to 100% scale (>80%: great, <25% is poor); QPPCaco: predicted apparent Caco-2 cell (a model for the gut-blood barrier) permeability in nm/sec (<25: poor, >500: great); QPlogHERG: predicted IC₅₀ value for blockage of HERG K+ channels (concern below -5); QPlogBB: predicted brain/blood partition coefficient (-3 to 12.0); CNS: predicted central nervous system activity on a –2 (inactive) to +2 (active) scale; QPPMDCK: predicted apparent MDCK cell permeability in nm/sec. MDCK cells are considered to be a good mimic for the blood-brain barrier (<25: poor, >500: great). QikProp predictions of Caco and MDCK are for nonactive transport; QPlogKp: predicted skin permeability, log Kp. (-8.0-1.0). QPlogKhsa: prediction of binding to human serum albumin (-1.5 to 1.5); #metab: number of likely metabolic reactions (1-8).