In silico and pharmacokinetic assessment of echinocystic acid effectiveness in Alzheimer's disease like pathology

Figures & data

Figure 1. Docked compound echinocystic acid with various targets related to Alzheimer's disease like pathology.

Table 1. Evaluation of in silico activity of echinocystic acid on Alzheimer's disease-like pathology.

Protein name	PDB ID	Binding energy (Kcal/mol)	Amino acid residues	Interaction
Bcl 2	5UUK	-6.07	GLUA76, GLUA80, PHEA79, ASNA72	Van der Waals, conventional hydrogen bond
IL6	1ALU	-6.0	ARGA179, LYSA66, META67	Conventional hydrogen bond
Cox 1	6Y3C	-5.45	LYSA473	Conventional hydrogen bond
NFκB	6M2D	-5.36	ARGA340, LYSA335	Conventional hydrogen bond
Cox 2	5F19	-1.85	LEUA390, ALA199	Van der Waals, conventional hydrogen bond
CREB	5I86	1.2	–	Unfavorable hydrogen bond
Il-1β	5R8Q	2.17	GLUA83, TYRA24	Conventional hydrogen bond
BDNF	1B8M	19.23	–	Unfavourable hydrogen bond
AchE	2GYU	57.59	THRA528, LYSA332	Van der Waals, conventional hydrogen bond
Caspase 3	4JJE	2010	–	Unfavourable hydrogen bond

Table 2. Pharmacokinetic profile of echinocystic acid.

Parameter	Predicted value
Water solubility (log mol/l)	-3.109
Intestinal absorption (human) (% absorbed)	94.939
P-glycoprotein I/II inhibitor	No
VDss (human) (log l/kg)	-1.217
Fraction unbound (human) (Fu)	0.065
BBB permeability (log BB)	-0.544
CNS permeability (log PS)	-1.448
CYP2D6 substrate	No
CYP3A4 substrate	Yes
CYP1A2/2C19/2C9/2D6/3A4 inhibitor	No
Total clearance (log ml/min/kg)	-0.043
Maximum tolerated dose (human) (log mg/kg/day)	0.034
hERG I/II inhibitor	No
Oral rat acute toxicity (LD50) (mol/kg)	2.227
Oral rat chronic toxicity (LOAEL) (log mg/kg/day)	1.808

Table 3. Physicochemical properties of echinocystic acid using swiss ADME.

Physicochemical Properties
Parameter	Value
Molecular weight	472.70 g/mol
Heavy atoms (n)	34
Arom. heavy atoms (n)	0
Fraction Csp3	0.90
Rotatable bonds (n)	1
H-bond acceptors (n)	4
H-bond donors (n)	3
Molar refractivity	137.82
TPSA	77.76 Å^2

Table 4. Lipophilicity profile of echinocystic acid profile using swiss ADME.

Lipophilicity
Parameter	Value
Log Po/w (iLOGP)	3.47
Log Po/w (XLOGP3)	6.88
Log Po/w (WLOGP)	6.20
Log Po/w (MLOGP)	4.97
Log Po/w (SILICOS-IT)	4.96
Consensus Log Po/w	5.30

Table 5. Water solubility profile of echinocystic acid using swiss ADME.

Water solubility
Parameter	Value
Log S (ESOL)	-7.04
Solubility	4.32e-05 mg/ml; 9.14e-08 mol/l
Class	Poorly soluble
Log S (Ali)	-8.32
Solubility	2.24e-06 mg/ml; 4.75e-09 mol/l
Class	Poorly soluble
Log S (SILICOS-IT)	-5.30
Solubility	2.37e-03 mg/ml; 5.02e-06 mol/l
Class	Moderately soluble

Table 6. Toxicity profile of echinocystic acid using OSIRIS.

Parameters	Echinocystic acid (scores)
Mutagenic	GREEN
Tumorigenic	GREEN
Irritant	GREEN
Reproductive effect	GREEN
TPSA	77.76
Drug likeness	-1.63
Drug score	0.33

Table 7. Evaluation of biological activity of echinocystic acid using PASS online.

Pa (active probability)	Pi (inactive probability)	Biological activity
0.827	0.005	Anti-inflammatory
0.786	0.006	Lipid metabolism regulator
0.779	0.004	Lipid peroxidase inhibitor
0.770	0.009	Hypolipemic
0.710	0.025	Acylcarnitine hydrolase inhibitor

Table 8. Bioactivity score of echinocystic acid using molinspiration.

Parameter	Value
GPCR ligand	0.23
Ion channel modulator	-0.12
Kinase inhibitor	-0.41
Nuclear receptor Ligand	0.72
Protease inhibitor	0.17
Enzyme inhibitor	0.58