Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Antiviral Evaluation
2.3. Molecular Docking
2.3.1. Influenza Virus A H1N1
2.3.2. Coxsackievirus B3
3. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Compound | Structure | CC50 1 (μM) | IC50 2 (μM) | SI 3 |
---|---|---|---|---|
2g | >543.0 | >543.0 | 1 | |
2j | >885 | >885 | 1 | |
2h | >492.9 | >492.9 | 1 | |
2k | 254 ± 19 4 | 43 ± 5 4 | 6 4 | |
2f | >337.5 | 96.3 ± 12.4 | 4 | |
2i | >471.2 | 57.5 ± 7.1 | 8 | |
2m | 311 ± 27 4 | 48 ± 6 4 | 6 4 | |
4g | >509.8 | 180.1 ± 19.9 | 3 | |
4j | 132 ± 9 | 42 ± 5 | 3 | |
4h | >465.4 | 186.2 ± 21.6 | 3 | |
4k | >744 4 | 212 ± 25 4 | 4 4 | |
4f | >324.0 | 103.9 ± 15.1 | 3 | |
4i | >446.0 | 297.3 ± 32.4 | 2 | |
4m | >719 | 30 ± 4 | 24 | |
5g | >468.3 | 187.3 ± 20.8 | 3 | |
5h | >430.6 | 114.8 ± 15.2 | 4 | |
5f | >307.7 | 91.6 ± 10.8 | 3 | |
5i | >414.0 | 24.3 ± 3.2 | 17 | |
11c | >349.0 | 29.2 ± 4.3 | 12 | |
11g | 104 ± 8 4 | 67 ± 8 4 | 2 4 | |
11e | >492.9 | 164.3 ± 19.2 | 3 | |
11h | 79 ± 6 | 15 ± 3 | 5 | |
11d | >338.0 | 119.3 ± 8.7 | 3 | |
11i | >592 4 | >592 4 | 1 4 | |
11f | >471.2 | >471.2 | 1 | |
11j | >787 | >787 | 1 | |
Rimantadine | 340 ± 16 | 77 ± 8 | 4 | |
Oseltamivir carboxylate | >200 | 0.3 ± 0.06 | >667 |
Compound | Structure | CC50 1 (μM) | IC50 2 (μM) | SI 3 |
---|---|---|---|---|
2g | >543.0 | >543.0 | 1 | |
2j | >1180 4 | >1180 4 | 1 4 | |
2h | >492.9 | >492.9 | 1 | |
2k | >1090 4,3 | >1090 4,3 | 1 4,3 | |
2f | 17.7 ± 0.6 | >12.4 | 1 | |
2i | >471.2 | >471.2 | 1 | |
2m | 656 ± 33 4,3 | 106 ± 11 4,3 | 6 4,3 | |
4g | 380.6 ± 26.1 | >169.9 | 2 | |
4j | 166 ± 12 4 | 133 ± 154 | 1 4 | |
4h | >465.4 | >465.4 | 1 | |
4k | 101 ± 8 4,3 | >82 4,3 | 1 4,3 | |
4i | >446.0 | >446.0 | 1 | |
4m | 101 ± 9 4,3 | >79 4,3 | 1 4,3 | |
5g | >468.3 | >468.3 | 1 | |
5h | >430.6 | >430.6 | 1 | |
5f | 17.8 ± 1.1 | >11.3 | 2 | |
5i | >414.0 | >414.0 | 1 | |
11e | 394.3 ± 21.1 | >164.3 | 2 | |
11g | 140 ± 10 4 | >34 4 | 4 4 | |
11f | >471.2 | >471.2 | 1 | |
11h | 525 ± 31 4 | >263 4 | 2 4 | |
Pleconaril | >1000 | 21.6 | 46 |
Compound | Structure | IC50 (µM) | |||
---|---|---|---|---|---|
Cancer Cell Lines | Normal Cell Line | ||||
M-HeLa 2 | HuTu-80 3 | PC-3 4 | WI-38 5 | ||
2f | 88.1 ± 7.4 | >100 | >100 | >100 | |
2i | 100 ± 8.5 | >100 | >100 | >100 | |
5f | 71.4 ± 6.3 | >100 | 66.8 ± 5.3 | >100 | |
5i | 71 ± 6.1 | >100 | >100 | >100 | |
5-Fluorouracil | 62.0 ± 4.9 | 65.2 ± 5.5 | 10.3 ± 0.8 | 82.5 ± 6.6 |
Compound | Structure | IC50 (µM) | −Ebind (kkal/mol) | Ligand–Protein Interactions |
---|---|---|---|---|
2i | 57.5 | 8.7 | H-bonding: Val122, Lys134, Lys137 | |
2i-TP | − | 8.8 | H-bonding: Tyr24, Val122, Lys134, Lys137, Arg196 π-cation: Lys34 | |
5i | 24.3 | 9.3 | H-bonding: Tyr24, Gly81, Leu106 π-cation: Mn2+, Lys134 | |
5i-TP | − | 9.1 | H-bonding: Tyr24, Gly81, Arg84, Lys137 π-π: Tyr24 | |
11c | 29.2 | 8.1 | H-bonding: Arg84, Leu106, Lys134, Lys137, Arg196 π-cation: Mn2+. |
Compound | Structure | IC50 (µM) | −Ebind (kkal/mol) | Ligand–Protein Interactions |
---|---|---|---|---|
2f | >12.4 | 8.3 | H-bonding: Ser209 (VP2) π-π: Tyr189 (VP1) | |
5f | >11.3 | 9.2 | H-bonding: Tyr143 (VP1), Ser190 (VP1), Arg196 (VP2) |
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Andreeva, O.V.; Garifullin, B.F.; Zarubaev, V.V.; Slita, A.V.; Yesaulkova, I.L.; Volobueva, A.S.; Belenok, M.G.; Man’kova, M.A.; Saifina, L.F.; Shulaeva, M.M.; et al. Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues. Molecules 2021, 26, 3678. https://doi.org/10.3390/molecules26123678
Andreeva OV, Garifullin BF, Zarubaev VV, Slita AV, Yesaulkova IL, Volobueva AS, Belenok MG, Man’kova MA, Saifina LF, Shulaeva MM, et al. Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues. Molecules. 2021; 26(12):3678. https://doi.org/10.3390/molecules26123678
Chicago/Turabian StyleAndreeva, Olga V., Bulat F. Garifullin, Vladimir V. Zarubaev, Alexander V. Slita, Iana L. Yesaulkova, Alexandrina S. Volobueva, Mayya G. Belenok, Maria A. Man’kova, Liliya F. Saifina, Marina M. Shulaeva, and et al. 2021. "Synthesis and Antiviral Evaluation of Nucleoside Analogues Bearing One Pyrimidine Moiety and Two D-Ribofuranosyl Residues" Molecules 26, no. 12: 3678. https://doi.org/10.3390/molecules26123678