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. 2021 Sep 25;22(19):10324. doi: 10.3390/ijms221910324

Table 4.

In silico physicochemical properties, ADMET, and drug-likeness.

Cpd
No.		 Physiochemical Parameters ADMET Drug-Likeness
LogP a MW b HBA c HBD d NROTB e TPSA f S g HIA h PPB i BBB j Caco2 k MDCK l CYP3A4 Inhibitor CYP2D6 Inhibitor LD50 m Lipinski n Veber o Egan p
15 4.02 778.95 8 0 12 177.58 5.57 × 10−6 98.10 100 1.88 34.90 1.49 Yes Non 1000 1 violation: MW > 500 2 violations: Rotors > 10, TPSA > 140 1 violation: TPSA > 131.6
16 2.44 682.87 8 0 12 177.58 0.004 99.19 93.48 0.515 32.69 0.04 Yes Non 1000 1 violation: MW > 500 2 violations: Rotors > 10, TPSA > 140 1 violation: TPSA > 131.6

a Log P: logarithm of compound partition coefficient between n-octanol and water. b M.Wt: molecular weight. c HBA: number of hydrogen bond acceptors. d HBD: number of hydrogen bond donors. e NROTB: number of rotatable bonds. f TPSA: polar surface area. Drug-like TPSA < 140–150 A2. g S: aqueous solubility (mg/L). h HIA: human intestinal absorption. HIA values < 20% (poorly absorbed), values ≈ 20–70% (moderately absorbed) and values > 70% (well absorbed) [82]. i PPB: plasma protein binding. PPB values < 90% (poorly bound) and values > 90% (strongly bound) [83]. j BBB: blood–brain barrier penetration. BBB values < 0.1 (low CNS absorption), values ≈ 0.1–2 (medium CNS absorption) and values > 2 (high CNS absorption) [84]. k Caco2: permeability through cells derived from human colon adenocarcinoma. PCaco2 values < 4 nm/sec (low permeability), values ≈ 4–70 nm/sec (medium permeability) and values > 70 nm/sec (high permeability) [85,86,87]. l MDCK: permeability through Madin-Darby Canin kidney cells. PMDCK values < 25 nm/sec (low permeability), values ≈ 25–500 nm/sec (medium permeability) and values > 500 nm/sec (high permeability) [86]. m LD50: the median lethal dose (mg/Kg). Toxicity classes according to GHS are: Class I: fatal if swallowed (LD50 ≤ 5), Class II: fatal if swallowed (5 < LD50 ≤ 50), Class III: toxic if swallowed (50 < LD50 ≤ 300), Class IV: harmful if swallowed (300 < LD50 ≤ 2000), Class V: may be harmful if swallowed (2000 < LD50 ≤ 5000), and Class VI: non-toxic (LD50 > 5000) [78]. n Lipinski rule: log P ≤ 5, M.Wt ≤ 500 Da, HBA ≤ 10 and HBD ≤ 5 [79]. o Veber rule: NROTB ≤ 10 and TPSA ≤ 140 [80]. p Egan’s rule: log P ≤ 5.88, TPSA ≤ 131.6 [81].