Table 9 Prediction of some of ADMET end points of compounds 3c and 4c using the using pkCSM server.

Parameters* (unite)	3c	4c	Doxorubicin
Absorption
Water solubility (log mol/L)	− 4.034	− 5.411	− 3.202
Caco2 permeability (log Papp in 10⁻⁶ cm/s)	0.327	0.271	0.403
Intestinal absorption (human)	87.39	90.99	62.63
Skin Permeability (log Kp)	− 2.76	− 2.73	− 2.73
P-glycoprotein substrate	Yes	No	Yes
P-glycoprotein I inhibitor	Yes	Yes	No
P-glycoprotein II inhibitor	Yes	Yes	No
Distribution
VDss (human) (log L/kg)	− 0.182	− 0.403	1.71
Blood–Brain Barrier (log BB)	− 1.223	0.238	− 1.559
CNS permeability (log PS)	− 2.53	− 1.85	− 4.366
Metabolism
CYP2D6 substrate	No	No	No
CYP3A4 substrate	Yes	Yes	No
CYP1A2 inhibitor	Yes	No	No
CYP2C19 inhibitor	Yes	Yes	No
CYP2C9 inhibitor	Yes	Yes	No
CYP2D6 inhibitor	No	No	No
CYP3A4 inhibitor	Yes	Yes	No
Excretion
Total Clearance (log ml/min/kg)	− 0.168	0.241	0.817
Renal OCT2 substrate	No	No	No
Toxicity
Ames mutagenicity	Yes	No	Yes
Max. tolerated dose (human) (log mg/kg/day)	0.5	0.584	0.488
hERG I inhibitor	No	No	No
hERG II inhibitor	Yes	Yes	Yes
Oral Rat Acute Toxicity (LD50, mol/kg)	2.641	3.039	3.693
Oral Rat Chronic Toxicity (log mg/kg_bw/day)	1.874	− 0.235	2.659
Hepatotoxicity	Yes	Yes	No
Skin Sensitization	No	No	No
T.Pyriformis toxicit (log ug/L)	0.314	0.285	0.285
Minnow toxicity (log mM)	− 0.731	− 7.277	7.759

*Solubility is classified by log S values: very soluble (> 0), extremely soluble (− 2 to 0), soluble (− 4 to − 2), moderately soluble (− 6 to − 4), weakly soluble (− 10 to − 6), and insoluble (< − 10). High Caco-2 permeability is indicated by log Papp > 0.9; low skin permeability by log Kp > − 2.5. Volume of distribution (VDss) is low if log VDss < − 0.15 and high if log VDss > 0.45. Compounds with log BB > 0.3 readily cross the blood–brain barrier, while those with log BB < − 1 are poorly distributed to the brain. Central nervous system (CNS) penetration is expected if log PS > − 2, but unlikely if log PS < − 3.

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