Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds
Abstract
:1. Introduction
2. Methodology
2.1. Protein Preparation
2.2. Virtual Screening
2.3. Molecular Docking
2.4. In Silico Physicochemical, Pharmacokinetics, Drug-Likeness and ADMET Prediction
2.5. Molecular Dynamics Simulation
3. Results and Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Descriptor/Properties | Value | ||
---|---|---|---|
ZINC153731 | ZINC69482055 | ZINC164387 | |
Molecular Weight | 178.187 | 358.434 | 267.275 |
Monoisotopic Mass | 178.062995 | 358.178025 | 267.032953 |
Rotatable Bonds | 2 | 1 | 0 |
Acceptors | 3 | 5 | 2 |
Donors | 1 | 1 | 1 |
cLogP | 1.5561 | 3.0513 | 4.6289 |
cLogS | −1.831 | −3.355 | −4.672 |
Total Surface Area | 76.271 | 264.17 | 177.93 |
Relative PSA | 0.24733 | 0.23553 | 0.1627 |
Polar Surface Area | 46.53 | 80.67 | 37.33 |
Drug-likeness | −4.3625 | 1.4711 | −7.4682 |
Mutagenic | none | none | high |
Tumorigenic | none | none | none |
Irritant | none | none | none |
Drug Score | 0.4833717 | 0.7209172 | 0.1100568 |
Property | Model Name | Predicted Value | Unit | |||
---|---|---|---|---|---|---|
ZINC164387 | ZINC69482055 | ZINC153731 | ||||
Absorption | Water solubility | −5.452 | −3.955 | −1.944 | log mol/L | |
Caco2 permeability | 1.527 | 1.292 | 1.189 | log Papp in 10−6 cm/s | ||
Intestinal absorption | 88.982 | 98.872 | 95.107 | % Absorbed | ||
Skin permeability | −2.544 | −4.244 | −2.503 | log Kp | ||
P-glycoprotein (P-gp) substrate | No | Yes | No | |||
P-gp I inhibitor | No | No | No | |||
P-gp II inhibitor | No | No | No | |||
Distribution | VDss (human) | 0.504 | 0.004 | −0.15 | log L/kg | |
Fraction unbound | 0.018 | 0.267 | 0.396 | Fu | ||
permeability | BBB | 0.588 | −0.133 | 0.125 | log BB | |
CNS | −1.264 | −2.807 | −1.937 | log PS | ||
Metabolism | substrate | CYP2D6 | No | No | No | |
CYP3A4 | Yes | No | No | |||
inhibitor | CYP1A2 | Yes | No | Yes | ||
CYP2C19 | Yes | No | No | |||
CYP2C9 | Yes | No | No | |||
CYP2D6 | No | No | No | |||
CYP3A4 | No | No | No | |||
Excretion | Total clearance | 0.155 | 1.074 | 0.71 | log mL/min/kg | |
Renal OCT2 substrate | Yes | No | No | |||
Toxicity | AMES toxicity | No | No | No | ||
Max. tolerated dose (human) | 0.143 | −0.361 | 0.931 | log mg/kg/day | ||
inhibitor | hERG I | No | No | No | ||
hERG II | No | No | No | |||
LD50 | 2.54 | 2.592 | 1.833 | mol/kg | ||
LOAEL | 1.024 | 2.062 | 2.535 | log mg/kg_bw/day | ||
Hepatotoxicity | No | No | No | |||
Skin Sensitization | No | No | No | |||
T. Pyriformis toxicity | 2.26 | 0.49 | 0.8 | log mM | ||
Minnow toxicity | 0.033 | 1.667 | 1.168 |
S. No. | Compounds | 2D Structure | Binding Energy (kcal/mol) | Inhibition Constant (µM) |
---|---|---|---|---|
1 | ZINC153731 | −11.53 | 10.9 | |
2 | ZINC69482055 | −10.67 | 13.32 | |
3 | ZINC164387 | −9.21 | 18.56 | |
4 | DFMO * | −7.25 | 28.85 |
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He, S.; Almalki, A.A.; Rafeeq, M.M.; Sain, Z.M.; Alqosaibi, A.I.; Alnamshan, M.M.; Al-Dhuayan, I.S.; Rahaman, A.; Zhang, Y.; Banjer, H.J.; et al. Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds. Molecules 2022, 27, 732. https://doi.org/10.3390/molecules27030732
He S, Almalki AA, Rafeeq MM, Sain ZM, Alqosaibi AI, Alnamshan MM, Al-Dhuayan IS, Rahaman A, Zhang Y, Banjer HJ, et al. Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds. Molecules. 2022; 27(3):732. https://doi.org/10.3390/molecules27030732
Chicago/Turabian StyleHe, Shan, Abdulraheem Ali Almalki, Misbahuddin M. Rafeeq, Ziaullah M. Sain, Amany I. Alqosaibi, Mashael M. Alnamshan, Ibtesam S. Al-Dhuayan, Abdul Rahaman, Yang Zhang, Hamsa Jameel Banjer, and et al. 2022. "Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds" Molecules 27, no. 3: 732. https://doi.org/10.3390/molecules27030732