Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis
Abstract
1. Introduction
2. Computational Methods
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Quantum Chemical Descriptor | (E)-1-(4-Methoxyphenyl)-3-(p-tolyl) prop-2-en-1-one | (E)-3-(4-Hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl) prop-2-en-1-one |
---|---|---|
μ | −8.723 eV | −8.171 eV |
n | 4.959 eV | 5.386 eV |
I | 11.202 eV | 10.855 eV |
A | 6.243 eV | 5.487 eV |
ω | 7.672 eV | 6.198 eV |
χ | 8.732 eV | 8.171 eV |
ζ | 0.202 eV | 0.186 eV |
Egap | 4.959 eV | 5.386 eV |
Complex | Total Energy (KJ/mole) | Energy HBond (KJ/mole) | Energy VDW (KJ/mole) | Amino Acid Residue HBond | Amino Acid Residue VDW Interactions |
---|---|---|---|---|---|
A-5OQW | −69.10 | 0 | −69.10 | None | Leu 307, Thr 308, Trp 310, Glu 314, Gln 319, Trp 323, Tyr 324 |
B-5OQW | −74.13 | −12.08 | −62.05 | Ser 278, Val 279, Trp 310 | Val 279, Gly 293, Glu 294, Asp 296, Trp 310 |
ADME Characteristics | Value-Answer |
---|---|
Formula | C15H12O5 |
Molecular weight | 272.25 g/mol |
Number of heavy atoms | 20 |
Number of rotatable bonds | 3 |
Number of Hydrogen bond acceptors | 5 |
Number of Hydrogen bond donors | 4 |
Molar refractivity | 74.34 |
Log Po/w | 1.90 |
Log S | −3.55 |
GI absorption | High |
BBB permeant | No |
CYP1A2 Inhibitor | Yes |
CYP2C19 Inhibitor | No |
CYP2C9 Inhibitor | Yes |
CYP2D6 Inhibitor | No |
CYP3A4 Inhibitor | Yes |
Log Kp | −5.96 cm/s |
Lipinski | Yes, 0 violation |
Bioavailability Score | 0.55 |
Lead-likeness | Yes |
Synthetic accessibility | 2.56 |
Pg Substrate | No |
Description | Prediction |
---|---|
AMES Toxicity | No |
Maximum Tolerated Dose | 0.373 (log mg/Kg/day) |
hERG I Inhibitor | No |
hERG II Inhibitor | Yes |
Oral Rat Acute Toxicity (LD50) | 2.193 (mol/Kg) |
Oral Rat Chronic Toxicity (LOAEL) | 2.690 (log mg/Kg_bw/day) |
Hepatotoxicity | No |
Skin Sensitization | No |
T. Pyriformis Toxicity | 0.318 (log ug/L) |
Minnow Toxicity | 0.752 (log mM) |
Non Cardiotoxic | 70% Confidence |
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Mavra, A.; Petrou, C.C.; Vlasiou, M.C. Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis. Molecules 2022, 27, 4825. https://doi.org/10.3390/molecules27154825
Mavra A, Petrou CC, Vlasiou MC. Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis. Molecules. 2022; 27(15):4825. https://doi.org/10.3390/molecules27154825
Chicago/Turabian StyleMavra, Angeliki, Christos C. Petrou, and Manos C. Vlasiou. 2022. "Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis" Molecules 27, no. 15: 4825. https://doi.org/10.3390/molecules27154825
APA StyleMavra, A., Petrou, C. C., & Vlasiou, M. C. (2022). Ligand and Structure-Based Virtual Screening in Combination, to Evaluate Small Organic Molecules as Inhibitors for the XIAP Anti-Apoptotic Protein: The Xanthohumol Hypothesis. Molecules, 27(15), 4825. https://doi.org/10.3390/molecules27154825