In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13
Abstract
:1. Introduction
2. Results and Discussion
2.1. Evalaution of Anti-Mtb Potenial of Benzofurans-1,3,4-Oxadiazoles Using Computational Approaches
Mycobacterium Tuberculosis
2.2. Molecular Docking Investigations of BF1–BF16 against the Pks13 Enzyme
2.3. Structure-Activity Relationship (SAR) of Bromobenzofuran-1,3,4-Oxadiazoles BF3, BF4, and BF8
2.4. ADMET and Drug-Likeness Studies of Benzofuran-1,3,4-Oxadiazoles BF1–BF16
2.5. MD Simulations Study of Benzofuran-1,3,4-oxadiazoles BF3, BF4, and BF8
2.6. MM-PBSA Investigations of the Most In Silico Bioactive Benzofuran-1,3,4-oxadiazoles
3. Materials and Methods
3.1. Chemistry
3.2. Molecular Docking of Benzofuran-1,3,4-oxadiazoles BF1–BF16
3.3. ADMET and Drug-Likeness Investigations of Benzofuran-1,3,4-oxadiazoles
3.4. MD Simulation Study of the Most In Silico Bioactive BF3, BF4, and BF8 Derivatives
3.5. MM-PBSA Binding Free Energy Calculations of the Most In Silico Bioactive BF3, BF4, and BF8 Derivatives
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compounds | Binding Affinities | Interacting Residues of Pks13 | Interaction Types |
---|---|---|---|
BF1 | −12.93 kcal/mol | ILE1643, TYR1663, HIS1632, HIS1699, ALA1667, TYR1674, | Carbon-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Alkyl, and Alkyl. |
BF2 | −12.71 kcal/mol | ASN1640, ILE1643, TYR1637, TYR1663, HIS1632, ALA1667, TYR1674, PHE1670 | C-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Pi Stacked, and Alkyl. |
BF3 | −14.23 kcal/mol | VAL1537, ALA1561, PHE1637, ARG1641, ILE1643, TYR1663, HIS1664, ALA1667, PHE1670, TYR1674, HIS1699 | Conventional H-bond, C-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Alkyl, Pi-Lone pair, Pi-Sulfur, Pi-Sigma, and Pi-Pi Stacked |
BF4 | −14.82 kcal/mol | VAL1537, SER1533, ALA1561, VAL1537, TYR1674, ILE1643, PHE1670, ALA1667 | Conventional H-bond, C-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Alkyl, Pi-Lone pair, Pi-Sulfur, Pi-Sigma, and Pi-Pi Stacked |
BF5 | −12.31 kcal/mol | ALA1561, TYR1663, ILE1643, HIS1664, TYR1674, ALA1667 | C-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Alkyl, Pi-Lone pair, and Alkyl. |
BF6 | −11.89 kcal/mol | SER1533, ALA1667, ALA1561, TYR1663, ILE1643, HIS1664, GLN1633, TYR1674 | Conventional H-bond, C-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Alkyl, Pi-Lone pair, Halogen, and Alkyl. |
BF7 | −12.23 kcal/mol | HIS1632, TYR1637, ILE1643, TYR1663, ALA1667, PHE1670, TYR1674 | Carbon-Hydrogen Bond, Van der Waals, Pi-Pi Stacked, Pi-Alkyl, and Alkyl. |
BF8 | −14.11 kcal/mol | VAL1537, ALA1561, TYR1663, ASN1640, ILE1643, PHE1670, ARG1641, ASP1644, HIS1664 | Conventional H-bond, C-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Alkyl, Pi-Lone pair, Amide-Pi Stacked |
BF9 | −13.44 kcal/mol | ILE1643, ALA1667, PHE1670, VAL1562, HIS1699, TYR1674, TYR1637 | Conventional H-bond, C-Hydrogen Bond, Van der Waals, Pi-Pi T-Shaped, Pi-Pi Stacked, Pi-Alkyl, and Alkyl |
TAM-16 (Standard) | −14.61 kcal/mol | SER1533, GLN1633, ASN1640, ASP1644, ILE1643, TYR1663, ALA1667, PHE1670, TYR1674 | Conventional H-bond, C-Hydrogen Bond, Van der Waals, Pi-Pi Stacked, Pi-Alkyl, Amide Pi-Stacked, Pi-Sigma, and Alkyl |
Nanoseconds | Pks13+BF3 | Pks13+BF4 | Pks13+BF8 |
---|---|---|---|
10 | −59.4 ± 149.6 | −956.2 ± 586.2 | −87.8 ± 235.6 |
20 | −135.2 ± 235.5 | −105.3 ± 387.4 | −508.9 ± 245.1 |
30 | −95.8 ± 269.3 | −912.3 ± 189.3 | −354.2 ± 245.3 |
40 | −570.3 ± 684.2 | −245.3 ± 245.6 | −150.8 ± 250.4 |
50 | −856.2 ± 345.6 | −856.3 ± 409.8 | −750.4 ± 150.6 |
60 | −135.2 ± 248.6 | −301.7 ± 204.8 | −723.3 ± 523.6 |
70 | −486.3 ± 367.3 | −501.1 ± 193.5 | −685.8 ± 351.2 |
80 | −648.8 ± 385.2 | −1101.3 ± 497.6 | −289.7 ± 487.5 |
90 | −329.2 ± 301.2 | −687.5 ± 260.1 | −350.4 ± 293.7 |
100 | −300.8 ± 283.2 | −423.4 ± 305.3 | −145.8 ± 354.6 |
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Irfan, A.; Faisal, S.; Zahoor, A.F.; Noreen, R.; Al-Hussain, S.A.; Tuzun, B.; Javaid, R.; Elhenawy, A.A.; Zaki, M.E.A.; Ahmad, S.; et al. In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13. Pharmaceuticals 2023, 16, 829. https://doi.org/10.3390/ph16060829
Irfan A, Faisal S, Zahoor AF, Noreen R, Al-Hussain SA, Tuzun B, Javaid R, Elhenawy AA, Zaki MEA, Ahmad S, et al. In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13. Pharmaceuticals. 2023; 16(6):829. https://doi.org/10.3390/ph16060829
Chicago/Turabian StyleIrfan, Ali, Shah Faisal, Ameer Fawad Zahoor, Razia Noreen, Sami A. Al-Hussain, Burak Tuzun, Rakshanda Javaid, Ahmed A. Elhenawy, Magdi E. A. Zaki, Sajjad Ahmad, and et al. 2023. "In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13" Pharmaceuticals 16, no. 6: 829. https://doi.org/10.3390/ph16060829
APA StyleIrfan, A., Faisal, S., Zahoor, A. F., Noreen, R., Al-Hussain, S. A., Tuzun, B., Javaid, R., Elhenawy, A. A., Zaki, M. E. A., Ahmad, S., & Abdellattif, M. H. (2023). In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13. Pharmaceuticals, 16(6), 829. https://doi.org/10.3390/ph16060829