Identification of Small Molecule Inhibitors against Mycobacteria in Activated Macrophages
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cluster | Compound | Structure | Name |
---|---|---|---|
Thiazole- hydrazine | 24 | 4-(4-chlorophenyl)-N-[(Z)-(4methoxyphenyl)methylideneamino]-1,3-thiazol-2-amine | |
25 | N-[(Z)-(4-chlorophenyl)methylideneamino]-4-phenyl-1,3-thiazol-2-amine | ||
26 | N-[(E)-benzylideneamino]-4-(4-methylphenyl)-1,3-thiazol-2-amine | ||
47 | N-[(Z)-(4-methylphenyl)methylideneamino]-4-phenyl-1,3-thiazol-2-amine | ||
Pyridine- hydrazide | 55 | N-[(5-hydroxy-2-adamantylidene)amino]pyridine-4-carboxamide | |
56 | N-[(Z)-[5-(2,3-dichlorophenyl)furan-2-yl]methylideneamino]pyridine-4-carboxamide | ||
57 | N-[(Z)-1-(2,3-dihydro-1,4-benzodioxin-3-yl)ethylideneamino]pyridine-3-carboxamide | ||
58 | N-[(Z)-3-phenylpropylideneamino]pyridine-4-carboxamide | ||
Triazole- carboxamides | 30 | 1-(4-ethylphenyl)-N-(3-fluorophenyl)-5-methyltriazole-4-carboxamide | |
31 | 1-(4-ethylphenyl)-5-methyl-N-(4-methylphenyl)triazole-4-carboxamide | ||
35 | N-(3-fluorophenyl)-1-(3-methoxyphenyl)-5-methyltriazole-4-carboxamide | ||
37 | 1-(3-methoxyphenyl)-5-methyl-N-(4-propoxyphenyl)triazole-4-carboxamide | ||
Pyrimidine | 19 | N-butyl-2-methyl-[1]benzofuro[3,2-d]pyrimidin-4-amine | |
36 | 4-(2-methylpiperidin-1-yl)-[1]benzofuro[3,2-d]pyrimidine | ||
50 | N-cyclopentylquinazolin-4-amine | ||
Phenyl- urea | 44 | 1-(3-chloro-4-fluorophenyl)-3-(4-methylphenyl)urea | |
46 | 1-(4-chlorophenyl)-3-(3-fluorophenyl)urea | ||
54 | 1-(3-chlorophenyl)-3-[2-(5-fluoro-1H-indol-3-yl)ethyl]urea | ||
Triazine diamine | 5 | 4-N-ethyl-2-N-propan-2-yl-6-pyrrolidin-1-yl-1,3,5-triazine-2,4-diamine | |
10 | 2-N-tert-butyl-6-(3,5-dimethylpyrazol- 1-yl)-4-N-propan-2-yl-1,3,5-triazine-2,4-diamine | ||
Benzamide | 16 | N-[[3-chloro-4-(4-propanoylpiperazin-1-yl)phenyl]carbamothioyl]benzamide | |
18 | N-(3-butan-2-yloxyphenyl)-4-fluorobenzamide | ||
Thiophene- carboxamide | 11 | N-(3-fluorophenyl)-5-methylthiophene-3-carboxamide | |
51 | 5-ethyl-N-pyridin-4-yl-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide | ||
Alcohol with piperazine | 17 | 1-(1-adamantylmethoxy)-3-(3-methylpiperidin-1-yl)propan-2-ol | |
42 | 1-tert-butoxy-3-[4-(5-chloro-2-methylphenyl)-1-piperazinyl]-2-propanol hydrochloride | ||
Thiourea | 48 | [1-(4-chlorophenyl)-2,5-dioxopyrrolidin-3-yl] N’-[(Z)-[(E)-4[4(dimethylamino)phenyl]but-3-en-2-ylidene]amino] carbamimidothioate | |
53 | [(Z)-[4-(1-adamantyl)phenyl]methylideneamino]thiourea | ||
Sulfone | 15 | 1-[(3,4-dichlorophenyl)methylsulfonyl]-4-methylpiperazine | |
49 | 4-methyl-N-(4-methylphenyl)piperidine-1-sulfonamide | ||
Pyridine- carboxamides | 4 | N’-(4-biphenylylmethylene)isonicotinohydrazide | |
Carboxylic acid | 6 | 7-(4carbamothioylpiperazin-1-yl)-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid | |
Aminothiazole | 7 | N-(3,4-dimethylphenyl)-4-pyridin-2-yl-1,3-thiazol-2-amine | |
Acetamide | 32 | N-[4-(4-acetylpiperazin-1-yl)-3-chlorophenyl]-2-(4-chlorophenoxy) acetamide | |
Imidazole | 40 | 1-(4-methyl-2-phenylimidazo[1,2-a]benzimidazol-1-yl)propan-1-one | |
Pyridine- thioether | 52 | 4-[2-(2-phenylethylsulfanyl)ethyl]pyridine |
Compound | THP-1 Cytotoxicity [μM] | Intracellular Killing in THP-1 Cells | MIC50 [μM] | ||||
---|---|---|---|---|---|---|---|
MAH104 | Mab19977 | MtbH37Ra | MAH104 | Mab19977 | MtbH37Ra | ||
4 | 32 | Yes | Yes | Yes | 10 | - | 3 |
5 | 32 | Yes | Yes | - | - | - | - |
6 | - | Yes | Yes | - | 3 | 32 | 10 |
7 | 10 | Yes | - | Yes | 10 | 10 | 10 |
10 | 32 | Yes | Yes | Yes | - | - | - |
11 | 32 | Yes | - | - | - | 32 | - |
15 | - | Yes | Yes | - | - | - | - |
16 | 10 | Yes | - | Yes | 32 | - | - |
17 | 32 | Yes | - | Yes | 100 | - | 10 |
18 | 32 | * | - | - | 100 | - | - |
19 | - | - | - | - | 100 | 100 | 10 |
24 | - | - | - | Yes | - | - | - |
25 | - | Yes | - | Yes | 32 | - | 10 |
26 | 32 | Yes | - | Yes | - | - | 10 |
30 | - | - | - | - | - | - | 10 |
31 | - | Yes | Yes | - | - | - | - |
32 | 32 | - | Yes | - | - | - | - |
35 | 32 | * | - | - | - | 100 | - |
36 | 32 | * | * | - | 100 | 100 | - |
37 | 32 | - | Yes | - | 100 | - | - |
40 | 32 | - | - | - | - | - | 10 |
42 | - | - | Yes | - | - | - | 10 |
44 | - | Yes | Yes | - | - | - | - |
46 | 32 | * | * | - | 10 | 32 | - |
47 | - | Yes | Yes | Yes | - | - | - |
48 | 32 | Yes | Yes | Yes | 10 | - | 10 |
49 | 32 | - | - | - | - | - | 10 |
50 | - | Yes | Yes | - | - | - | - |
51 | 32 | - | Yes | - | - | - | 10 |
52 | - | Yes | Yes | - | 10 | - | - |
53 | 32 | Yes | Yes | Yes | - | - | 10 |
54 | 10 | Yes | Yes | - | 32 | - | 10 |
55 | - | * | - | Yes | 32 | - | 10 |
56 | 32 | Yes | - | Yes | 100 | 10 | - |
57 | 32 | Yes | - | Yes | 32 | - | - |
58 | - | * | - | - | 100 | - | - |
Compound | MIC50 [μM] | |||||||
---|---|---|---|---|---|---|---|---|
MAH104 | NJH 0133 | MAH B | MAH C | Mab19977 | DNA 01627 | NR49093 Strain DJO44274 | NR44273 Strain 4529 | |
4 | 10 | 10 | 100 | 10 | - | - | - | - |
6 | 3 | 3 | - | 3 | 32 | 32 | 32 | 32 |
7 | 10 | 10 | - | - | 10 | 10 | 10 | 10 |
11 | - | - | - | - | 32 | 32 | 32 | 32 |
16 | 32 | 32 | 100 | 100 | - | - | - | 100 |
17 | 100 | 100 | 100 | - | - | - | - | - |
18 | 100 | 100 | 100 | 100 | - | - | - | 100 |
19 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
25 | 32 | - | - | - | - | - | - | - |
35 | - | - | - | - | 100 | 100 | 32 | 32 |
36 | 100 | 100 | - | 100 | 100 | 100 | 32 | 32 |
37 | 100 | 100 | - | 100 | - | - | - | - |
46 | 10 | 10 | - | 10 | 32 | 32 | 10 | 32 |
48 | 10 | 10 | 32 | 32 | - | - | - | - |
52 | 10 | - | - | - | - | - | - | - |
54 | 32 | 100 | - | - | - | - | - | - |
55 | 32 | 10 | 10 | 10 | - | - | - | - |
56 | 100 | 10 | 10 | 10 | 10 | 10 | 32 | 32 |
57 | 32 | 10 | 10 | 100 | - | - | - | - |
58 | 100 | 10 | 10 | 100 | - | - | - | - |
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Vande Voorde, R.; Dzalamidze, E.; Nelson, D.; Danelishvili, L. Identification of Small Molecule Inhibitors against Mycobacteria in Activated Macrophages. Molecules 2022, 27, 5824. https://doi.org/10.3390/molecules27185824
Vande Voorde R, Dzalamidze E, Nelson D, Danelishvili L. Identification of Small Molecule Inhibitors against Mycobacteria in Activated Macrophages. Molecules. 2022; 27(18):5824. https://doi.org/10.3390/molecules27185824
Chicago/Turabian StyleVande Voorde, Rebecca, Elizaveta Dzalamidze, Dylan Nelson, and Lia Danelishvili. 2022. "Identification of Small Molecule Inhibitors against Mycobacteria in Activated Macrophages" Molecules 27, no. 18: 5824. https://doi.org/10.3390/molecules27185824
APA StyleVande Voorde, R., Dzalamidze, E., Nelson, D., & Danelishvili, L. (2022). Identification of Small Molecule Inhibitors against Mycobacteria in Activated Macrophages. Molecules, 27(18), 5824. https://doi.org/10.3390/molecules27185824