In Vitro Screening of an In-House Library of Structurally Distinct Chemotypes Towards the Identification of Novel SARS-CoV-2 Inhibitors
Abstract
:1. Introduction
2. Results and Discussion
2.1. Design of the Study
2.2. Chemistry
2.3. Biological Studies and SARS-CoV-2
3. Materials and Methods
3.1. Chemistry
3.1.1. General Information
3.1.2. General Procedure for the Preparation of Thiosemicarbazones
3.2. Cytotoxicity Assay
3.3. Vero E6 Cells Infection, Treatment and Evaluation of the Antiviral Activity
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Compound | Vero E6 CC50 (µM) a | SARS-CoV-2 IC50 (µM) a | S.I. |
---|---|---|---|
1 | 3.14 | >2 | |
2 | 2.81 | 1.5 | 1.9 |
3 | 10.5 | 4.0 | 2.6 |
4 | 2.19 | >1 | |
5 | 3.20 | >2 | |
6 | 5.58 | >3 | |
7 | 2.62 | (20.5%) b | |
8 | 1.74 | NA | |
9 | 1.88 | NA | |
10 | 44.0 | 2.2 | 20 |
11 | 74.5 | 3.7 | 20.1 |
12 | >100 | >100 | |
13 | 96.1 | 20.0 | 4.8 |
14 | 70.0 | 12.2 | 5.7 |
15 | 67.1 | 14.9 | 4.5 |
16 | 37.7 | >20 | |
17 | 191.9 | >60 | |
18 | 107.4 | 28.1 | 3.8 |
19 | 76.3 | 15.3 | 5.0 |
20 | 19.4 | 6.95 | 2.8 |
21 | 25.4 | >20 | |
22 | 26.8 | >20 | |
23 | >100 | 95.6 | >1.1 |
24 | 32.9 | >10 | |
25 | >100 | 90.1 | >1.1 |
CQ | 96.3 | 8.50 | 11.3 |
Cpd | Mean PFU/mL (% Replication) at the Indicated μM Concentrations | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Untreated Infected Cells | 0.7 | 1.9 | 2.2 | 5.6 | 6.7 | 16.7 | 20 | 25 | 40 | 50 | |
10 | 102.5 (100) | - | 83.5 (84.5) | - | 42.0 (40.9) | - | 10.0 (9.8) | - | 0.0 (0) | - | - |
11 | 63.0 (100) | - | 61.0 (96.8) | - | 26.3 (41.8) | - | 3.0 (4.8) | - | - | - | 0.0 (0) |
CQ | 85.0 (100) | - | 73.3 (86.2) | - | 54.3 (63.8) | - | 0.0 (0) | - | - | - | 0.80 (0) |
18 | 44.5 (100) | - | - | 28 (69.9) | - | 20 (44.9) | - | 13 (29.2) | - | 1 (2.2) | - |
20 | 53 (100) | 67 (>100) | - | 57 (>100) | - | 34 (63) | - | 3 (5) | - | - | - |
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Tonelli, M.; Sparatore, A.; Bassanini, I.; Francesconi, V.; Sparatore, F.; Maina, K.K.; Delbue, S.; D’Alessandro, S.; Parapini, S.; Basilico, N. In Vitro Screening of an In-House Library of Structurally Distinct Chemotypes Towards the Identification of Novel SARS-CoV-2 Inhibitors. Pharmaceuticals 2024, 17, 1668. https://doi.org/10.3390/ph17121668
Tonelli M, Sparatore A, Bassanini I, Francesconi V, Sparatore F, Maina KK, Delbue S, D’Alessandro S, Parapini S, Basilico N. In Vitro Screening of an In-House Library of Structurally Distinct Chemotypes Towards the Identification of Novel SARS-CoV-2 Inhibitors. Pharmaceuticals. 2024; 17(12):1668. https://doi.org/10.3390/ph17121668
Chicago/Turabian StyleTonelli, Michele, Anna Sparatore, Ivan Bassanini, Valeria Francesconi, Fabio Sparatore, Kevin K. Maina, Serena Delbue, Sarah D’Alessandro, Silvia Parapini, and Nicoletta Basilico. 2024. "In Vitro Screening of an In-House Library of Structurally Distinct Chemotypes Towards the Identification of Novel SARS-CoV-2 Inhibitors" Pharmaceuticals 17, no. 12: 1668. https://doi.org/10.3390/ph17121668
APA StyleTonelli, M., Sparatore, A., Bassanini, I., Francesconi, V., Sparatore, F., Maina, K. K., Delbue, S., D’Alessandro, S., Parapini, S., & Basilico, N. (2024). In Vitro Screening of an In-House Library of Structurally Distinct Chemotypes Towards the Identification of Novel SARS-CoV-2 Inhibitors. Pharmaceuticals, 17(12), 1668. https://doi.org/10.3390/ph17121668