TABLE 7.

ADME/T study of the identified best-binding compounds from C. gigantea and C. affinis against DHFR, KOR, and COX-2 macromolecules.

Property	Model name (Unit)	C1/C4	C2a	C2b	C3	C5	C6
Absorption	Water solubility (log mol/L)	−3.386	−6.499	−6.531	−6.044	−3.975	−3.114
	CaCo2 permeability (log Papp in 10–6 cm/s)	−0.045	1.227	1.226	0.362	0.91	0.389
	Intestinal absorption (human) (% absorbed)	88.746	94.062	93.733	90.234	94.821	84.522
	Skin permeability (log Kp)	−2.741	−2.814	−2.811	−2.814	−2.744	−2.735
	P-glycoprotein substrate	Yes	No	No	No	Yes	Yes
	P-glycoprotein I inhibitor	No	Yes	Yes	Yes	No	No
	P-glycoprotein II inhibitor	Yes	Yes	Yes	Yes	Yes	No
Distribution	VDss (human) (log L/kg)	−0.104	0.266	0.268	−0.288	0.375	0.201
	Fraction unbound (human) (Fu)	0.083	0	0	0.123	0.112	0.067
	BBB permeability (log BB)	−0.788	0.674	0.667	−0.911	−0.234	−1.192
	CNS permeability (log PS)	−3.135	−1.773	−1.773	−3.365	−1.816	−2.434
Metabolism	CYP2D6 substrate	No	No	No	No	No	No
	CYP3A4 substrate	Yes	Yes	Yes	Yes	No	No
	CYP1A2 inhibitor	Yes	No	No	Yes	Yes	Yes
	CYP2C19 inhibitor	Yes	No	No	No	Yes	No
	CYP2C9 inhibitor	Yes	No	No	No	Yes	Yes
	CYP2D6 inhibitor	No	No	No	No	Yes	No
	CYP3A4 inhibitor	No	No	No	No	Yes	Yes
Excretion	Total clearance (log mL/min/kg)	0.569	0.119	−0.044	2.04	0.076	0.458
	Renal OCT2 substrate	No	No	No	No	No	No
Toxicity	AMES toxicity	No	No	No	No	No	No
	Max. tolerated dose (human) (log mg/kg/day)	−0.048	−0.571	−0.56	0.193	0.286	0.82
	hERG I inhibitor	No	No	No	No	No	No
	hERG II inhibitor	No	Yes	Yes	No	Yes	No
	Oral rat acute toxicity (LD50) (mol/kg)	2.283	2.467	2.478	1.734	2.318	2.563
	Oral rat chronic toxicity (LOAEL) (log mg/kg_bw/day)	2.152	0.856	0.873	2.897	0.992	1.516
	Hepatotoxicity	No	No	No	No	No	No
	Skin sensitization	No	No	No	Yes	No	No
	Tetrahymena pyriformis toxicity (log ug/L)	0.371	0.384	0.383	0.617	0.434	0.323
	Minnow toxicity (log mM)	1.32	−1.309	−1.345	−0.969	−0.102	1.498
Drug-likeness	Bioavailability score (%)	0.55	0.55	0.55	0.55	0.55	0.55
	Lipinski’s Rule of Five	Yes; 0 violation	No; 2 violations: MW > 350, XLOGP3>3.5	No; 2 violations: MW > 350, XLOGP3>3.5	No; 3 violations: MW > 350, Rotors>7, XLOGP3>3.5	No; 1 violation: XLOGP3>3.5	Yes; 0 violation