Table 2.

Physicochemical and pharmacokinetic properties of ART-THY hybrids, parental and control compounds

Compound	MW (g/mol)	N.RB	N.HBAs	N.HBDs	Physicochemical properties				Pharmacokinetics
					TPSA at pH 7.4 (Å2)	Lipophilicity	Water solubility at pH 7.4		Absorption		Distribution
						log P	log S	mol/L	HIA (%)	PCaco-2 (nm/s)	PPB (%)	BBB (Cbrain/Cblood)
Parental ligands
ART	282.33	0	5	0	53.99	1.68	− 2.69	0.0020	96.31	30.32	93.36	1.30
ARA	384.42	5	8	1	103.35	1.70	− 1.62	0.0238	83.94	13.21	90.61	0.01
THY	164.20	1	2	0	34.14	2.51	− 2.66	0.0021	99.28	23.03	100.00	1.78
Artemisinin–thymoquinone hybrids
T1	588.69	11	10	0	123.66	4.69	− 6.69	0.0076	97.00	21.18	93.30	0.02
T2	602.71	12	10	0	123.66	5.15	− 7.00	0.0037	97.52	24.18	94.30	0.03
T3	574.66	10	10	0	123.66	4.24	− 6.38	0.0002	96.42	22.11	92.79	0.02
T4	530.65	8	8	0	97.36	4.79	− 6.83	0.0001	99.10	36.05	93.54	0.07
T5	544.68	9	8	0	97.36	5.24	− 7.13	0.0225	99.30	40.17	94.56	0.06
T6	488.61	6	7	0	80.29	4.90	− 6.53	0.0005	99.12	46.47	96.20	0.06
T7	502.64	7	7	0	80.29	5.36	− 6.84	0.0775	99.12	49.14	98.43	0.09
Control-ligands
ANK	509.55	10	9	3	176.34	1.83	− 3.37	0.0004	46.52	17.57	87.45	0.04
AZT	748.996	7	13	5	182.48	2.45	− 3.33	0.0004	69.32	31.40	14.49	0.06
BRT	371.42	4	6	1	120.56	0.40	− 0.14	0.7179	93.54	3.08	78.87	0.00
CLQ	319.88	8	3	1	30.61	4.53	− 4.59	0.0095	98.05	56.61	92.53	7.73
RDS	602.585	14	9	4	203.55	1.71	− 3.18	0.0006	53.50	3.26	81.26	0.04

AZT azithromycin, BRT baricitinib, RDS remdesivir, ANK anakinra, CLQ chloroquine, ART artemisin, ARA artemisin acid, THY thymoquinone