Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemistry
2.1.1. General Information
2.1.2. General Procedure for Ethyl 6-halogenobenzo[b]thiophene-2-carboxylate (4)
Ethyl 6-chlorobenzo[b]thiophene-2-carboxylate (4a)
Ethyl 6-fluorobenzo[b]thiophene-2-carboxylate (4b)
2.1.3. Procedure for Ethyl 6-(trifluoromethyl)benzo[b]thiophene-2-carboxylate (4c)
Ethyl 6-(trifluoromethyl)benzo[b]thiophene-2-carboxylate (4c)
2.1.4. Procedure for Ethyl 6-chlorobenzofuran-2-carboxylate (4d)
Ethyl 6-chlorobenzofuran-2-carboxylate (4d)
2.1.5. General Procedure for Benzo[b]thiophene-2-carboxylic Acids (1)
6-Chlorobenzo[b]thiophene-2-carboxylic acid (1b)
6-Fluorobenzo[b]thiophene-2-carboxylic acid (1c)
6-(Trifluoromethyl)benzo[b]thiophene-2-carboxylic acid (1d)
6-Chlorobenzofuran-2-carboxylic acid (1e)
2.1.6. General Procedure for Tert-butyl 2-(benzo[b]thiophene-2-carbonyl)hydrazine-1-carboxylates (2)
Tert-butyl-2-(benzo[b]thiophene-2-carbonyl)hydrazine-1-carboxylate (2a)
Tert-butyl-2-(6-chlorobenzo[b]thiophene-2-carbonyl)hydrazine-1-carboxylate (2b)
Tert-butyl-2-(6-fluorobenzo[b]thiophene-2-carbonyl)hydrazine-1-carboxylate (2c)
Tert-butyl-2-(6-(trifluoromethyl)benzo[b]thiophene-2-carbonyl)hydrazine-1-carboxylate (2d)
Tert-butyl-2-(6-chlorobenzofuran-2-carbonyl)hydrazine-1-carboxylate (2e)
2.1.7. General Procedure for N-Acylhydrazones Derivatives (I, II and III)
(E)-N’-(Benzo[d][1,3]dioxol-5-ylmethylene)benzo[b]thiophene-2-carbohydrazide (I.a)
(E)-N’-(4-(Dimethylamino)benzylidene)benzo[b]thiophene-2-carbohydrazide (I.b)
(E)-N’-(Pyridin-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (I.c)
(E)-N’-(Pyridin-3-ylmethylene)benzo[b]thiophene-2-carbohydrazide (I.d)
(E)-N’-(Pyridin-4-ylmethylene)benzo[b]thiophene-2-carbohydrazide (I.e)
(E)-N’-(3-Hydroxybenzylidene)benzo[b]thiophene-2-carbohydrazide (I.f)
(E)-N’-(4-Hydroxybenzylidene)benzo[b]thiophene-2-carbohydrazide (I.g)
(E)-N’-(4-Hydroxy-3-methoxybenzylidene)benzo[b]thiophene-2-carbohydrazide (I.h)
(E)-N’-(4-Chlorobenzylidene)benzo[b]thiophene-2-carbohydrazide (I.i)
(E)-N’-(4-Fluorobenzylidene)benzo[b]thiophene-2-carbohydrazide (I.j)
(E)-N’-(3-Nitrobenzylidene)benzo[b]thiophene-2-carbohydrazide (I.k)
(E)-N’-(4-Nitrobenzylidene)benzo[b]thiophene-2-carbohydrazide (I.l)
(E)-2-((2-(Benzo[b]thiophene-2-carbonyl)hydrazono)methyl)benzoic acid (I.m)
(E)-3-((2-(Benzo[b]thiophene-2-carbonyl)hydrazineylidene)methyl)benzoic acid (I.n)
(E)-4-((2-(Benzo[b]thiophene-2-carbonyl)hydrazono)methyl)benzoic acid (I.o)
(E)-N’-(Benzo[d][1,3]dioxol-5-ylmethylene)-6-chlorobenzo[b]thiophene-2-carbohydrazide (II.a)
(E)-6-Chloro-N’-(pyridin-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (II.b)
(E)-N’-(Benzo[d][1,3]dioxol-5-ylmethylene)-6-fluorobenzo[b]thiophene-2-carbohydrazide (II.c)
(E)-6-Fluoro-N’-(pyridin-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (II.d)
(E)-N’-((1H-Imidazol-4-yl)methylene)-6-chlorobenzo[b]thiophene-2-carbohydrazide (III.a)
(E)-6-Chloro-N’-(furan-2-ylmethylene)benzo[b]thiophene-2-carbohydrazide (III.b)
(E)-6-Chloro-N’-((5-(hydroxymethyl)furan-2-yl)methylene)benzo[b]thiophene-2-carbohydrazide (III.c)
(E)-6-Chloro-N’-(pyridin-2-ylmethylene)benzofuran-2-carbohydrazide (III.e)
(E)-N’-(Pyridin-2-ylmethylene)-6-(trifluoromethyl)benzo[b]thiophene-2-carbohydrazide (III.f)
2.1.8. Procedure for N’-(Pyridin-2-ylmethyl)benzo[b]thiophene-2-carbohydrazide (I.p)
N’-(Pyridin-2-ylmethyl)benzo[b]thiophene-2-carbohydrazide (I.p)
2.1.9. Procedure for Pyridine 2-aldoxime (6)
Pyridine 2-aldoxime (6)
2.1.10. Procedure for (E)-Picolinaldehyde O-(6-chlorobenzo[b]thiophene-2-carbonyl) oxime (III.d)
(E)-Picolinaldehyde O-(6-chlorobenzo[b]thiophene-2-carbonyl) oxime (III.d)
2.2. Biological Assays
2.2.1. Minimum Inhibitory Concentration (MIC) Evaluation
2.2.2. Cytotoxicity Assay
3. Results and Discussion
3.1. Synthesis and Biological Evaluation of Series I—Benzo[b]thiophene-2-Acylhydrazones
3.2. Synthesis and Biological Evaluation of Series II—6-Halogenobenzo[b]thiophene-2-Acylhydrazones
3.3. Synthesis and Biological Evaluation of Series III—Structural Modifications of II.b
3.4. Cytotoxicity Assay of II.b
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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Name | Structure | LogP | MIC (µg/mL) | ||
---|---|---|---|---|---|
ATCC 29213 a | SF8300 b | ST20171643 c | |||
I.a | | 4.20 | 32 | 64 | 16 |
I.b | | 4.41 | >256 | >256 | >256 |
I.c | | 3.13 | 16 | 16 | 16 |
I.d | | 3.07 | >256 | >256 | >256 |
I.e | | 3.02 | >256 | >256 | >256 |
I.f | | 3.80 | >256 | >256 | ND |
I.g | | 3.83 | >256 | >256 | >256 |
I.h | | 3.64 | >256 | >256 | >256 |
I.i | | 4.98 | 128 | 128 | 128 |
I.j | | 4.47 | >256 | >256 | 128 |
I.k | | 4.24 | >256 | >256 | ND |
I.l | | 4.26 | 64 | 64 | 32 |
I.m | | 3.83 | 256 | >256 | >256 |
I.n | | 4.19 | >256 | >256 | 256 |
I.o | | 4.22 | >256 | >256 | 256 |
I.p | | 2.33 | 64 | 64 | 64 |
Name | Structure | LogP | MIC (µg/mL) | ||
---|---|---|---|---|---|
ATCC 29213 a | SF8300 b | ST20171643 c | |||
II.a | | 4.85 | >256 | >256 | >256 |
II.b | | 3.79 | 4 | 4 | 4 |
II.c | | 4.33 | >256 | >256 | >256 |
II.d | | 3.27 | 32 | 16 | 16 |
Name | Structure | LogP | MIC (µg/mL) | ||
---|---|---|---|---|---|
ATCC 29213 a | SF8300 b | ST20171643 c | |||
III.a | | 3.19 | 256 | 64 | 64 |
III.b | | 4.22 | >256 | 256 | 256 |
III.c | | 3.79 | >256 | 256 | 256 |
III.d | | 3.89 | >256 | >256 | >256 |
III.e | | 3.15 | >256 | 256 | 128 |
III.f | | 4.01 | 32 | 8 | 16 |
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Barbier, T.; Barbry, A.; Magand, J.; Badiou, C.; Davy, F.; Baudouin, A.; Queneau, Y.; Dumitrescu, O.; Lina, G.; Soulère, L. Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus. Biomolecules 2022, 12, 131. https://doi.org/10.3390/biom12010131
Barbier T, Barbry A, Magand J, Badiou C, Davy F, Baudouin A, Queneau Y, Dumitrescu O, Lina G, Soulère L. Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus. Biomolecules. 2022; 12(1):131. https://doi.org/10.3390/biom12010131
Chicago/Turabian StyleBarbier, Thibaut, Alexia Barbry, Jérémy Magand, Cédric Badiou, Floriane Davy, Anne Baudouin, Yves Queneau, Oana Dumitrescu, Gérard Lina, and Laurent Soulère. 2022. "Synthesis and Biological Evaluation of Benzo[b]thiophene Acylhydrazones as Antimicrobial Agents against Multidrug-Resistant Staphylococcus aureus" Biomolecules 12, no. 1: 131. https://doi.org/10.3390/biom12010131