Alkaloids from Cryptolepis sanguinolenta as Potential Inhibitors of SARS-CoV-2 Viral Proteins: An In Silico Study

Table 4

QSAR and drug-likeness profile predicted for the Cryptolepis sanguinolenta alkaloids from the SwissADME and ADMETlab web servers.

Ligand	MW	HBA	HBD	TPSA	cLogPo/w	ESOL logs	ESOL class	GI abs.	LogKp (S.P.)	LP.V	LD.V	SA	-score
11-Isopropylcryptolepine	276.38	0	1	19.03	4.11	-5.1	Moderately soluble	High	-4.51	0	1	3.5	-0.62
Biscryptolepine	468.59	0	2	38.06	5.23	-7.37	Poorly soluble	High	-4.42	1	2	5.46	-0.86
Cryptoheptine	246.26	3	1	46.01	2.95	-4.06	Moderately soluble	High	-5.56	0	1	2.43	-0.49
Cryptolepicarboline	397.47	1	0	22.75	5.57	-6.99	Poorly soluble	Low	-4.18	1	2	2.99	-0.99
Cryptolepine	232.28	1	0	17.82	3.29	-4.08	Moderately soluble	High	-5.35	0	1	1.71	-0.69
Cryptolepinone	248.28	1	1	37.79	2.97	-4.29	Moderately soluble	High	-5.28	0	2	2.08	-0.20
Cryptomisrine	468.57	1	3	56.92	4.94	-8.00	Poorly soluble	High	-3.70	1	2	5.01	-0.48
Cryptoquindoline	448.52	2	0	35.64	5.92	-7.53	Poorly soluble	Low	-4.24	1	2	3.2	-1.18
Cryptospirolepine	504.58	1	1	45.96	5.63	-7.64	Poorly soluble	Low	-4.82	0	2	4.95	-0.34
Hydroxycryptolepine	250.3	1	2	39.26	2.47	-3.65	Soluble	High	-5.95	0	0	3.17	-0.24
Isocryptolepine	232.28	1	0	17.82	3.25	-4.05	Moderately soluble	High	-5.38	0	1	1.44	-0.84
Neocryptolepine	232.28	1	0	17.82	3.47	-4.32	Moderately soluble	High	-5.08	0	2	1.56	-0.38
Quindoline	217.25	2	0	25.78	1.94	-4.17	Moderately soluble	High	-5.10	0	2	1.57	-1.03

MW: molecular weight; HBA: hydrogen bond acceptor; HBD: hydrogen bond donor; TPSA: topological polar surface area; cLogP_o/w: lipophilicity; ESOL logs: water solubility; ESOL class: classification of water solubility; GI abs.: gastrointestinal absorption; LogK_p (S.P.): skin permeability; LP.V: number of Lipinski’s rules violated; LD.V: lead-likeness violation; SA: synthetic ability; -score: drug-likeness model score. All alkaloids violated none or only one of Lipinski’s rules. Cryptomisirine donates the most hydrogen bonds followed by biscryptolepine and hydroxycryptolepine. Cryptoheptine had the ability to accept the most hydrogen bonds followed by cryptoquindoline and quindoline. With a similar molecular landscape, all 13 alkaloids were largely hydrophobic, with most being moderately soluble to poorly soluble. Only hydroxycryptolepine was completely soluble. All ligands have the ability to cross the blood-brain barrier with most having high gastrointestinal absorption indices.