N-(2-Arylmethylthio-4-Chloro-5-Methylbenzenesulfonyl)amide Derivatives as Potential Antimicrobial Agents—Synthesis and Biological Studies
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Antimicrobial Activity Agianst Reference Microbial Strains
2.3. Antibacterial Activity Against Clinical Methicillin-Resistant and Methicillin-Sensitive S. aureus Strains
2.4. Inhibition of Biofilm Formation
2.5. Cytotoxic Activity
3. Materials and Methods
3.1. Synthesis
3.1.1. General Procedure for the Synthesis of N-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)-3-cyclohexylpropanamides (8–12)
N-(2-Benzylthio-4-chloro-5-methylbenzenesulfonyl)-3-cyclohexylpropanamide (8)
N-[4-Chloro-5-methyl-2-(4-trifluoromethylbenzylthio)benzenesulfonyl]-3-cyclohexylpropanamide (9)
N-[4-Chloro-5-methyl-2-(3-trifluoromethylbenzylthio)benzenesulfonyl]-3-cyclohexylpropanamide (10)
N-[4-Chloro-5-methyl-2-(naphthalen-1-ylmethylthio)benzenesulfonyl]-3-cyclohexylpropanamide (11)
N-[4-Chloro-5-methyl-2-(naphthalen-2-ylmethylthio)benzenesulfonyl]-3-cyclohexylpropanamide (12)
3.1.2. General Procedure for the Synthesis of N-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)cinnamamides (13–17)
N-{[2-(Benzylthio)-4-chloro-5-methylphenyl]sulfonyl}cinnamamide (13)
N-[4-Chloro-5-methyl-2-(4-trifluoromethylbenzylthio)benzenesulfonyl]cinnamamide (14)
N-[4-Chloro-5-methyl-2-(3-trifluoromethylbenzylthio)benzenesulfonyl]cinnamamide (15)
N-[4-Chloro-5-methyl-2-(naphthalen-1-ylmethylthio)benzenesulfonyl]cinnamamide (16)
N-[4-Chloro-5-methyl-2-(naphthalen-1-ylmethylthio)benzenesulfonyl]cinnamamide (17)
3.2. Bacterial Reference and Clinical Strains
3.3. Antimicrobial Assay
3.4. Biofilm Inhibition Assay for 10 and 16
3.5. Cell Culture and Cell Viability Assay
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Compound | S. aureus ATCC 6538 | S. aureus ATCC 43300 | S. epidermidis PCM 2118 | E. faecalis ATCC 11420 | ||||
---|---|---|---|---|---|---|---|---|
(µg/mL) | ||||||||
MIC | MBC | MIC | MBC | MIC | MBC | MIC | MBC | |
8 | 32 | >128 | 16 | >128 | 8 | 32 | 128 | >128 |
9 | 8 | >128 | 4 | >128 | 4 | 8 | 8 | >128 |
10 | 8 | 64 | 8 | 16 | 8 | 8 | 8 | 64 |
11 | 8 | >128 | 8 | >128 | 4 | >128 | 8 | >128 |
12 | 8 | 128 | 8 | >128 | 4 | 128 | 32 | >128 |
13 | 32 | >128 | 32 | >128 | 32 | >128 | >128 | >128 |
14 | 8 | 128 | 8 | 128 | 8 | 16 | 16 | >128 |
15 | 8 | 128 | 8 | 128 | 8 | 8 | 16 | >128 |
16 | 4 | >128 | 4 | >128 | 4 | 4 | 8 | >128 |
17 | 8 | >128 | 4 | >128 | 4 | >128 | 128 | >128 |
Compound | E. coli ATCC 11229 | P. aeruginosa ATCC 15442 | P. vulgaris NCTC 4635 | C. albicans ATCC 10231 | ||||
---|---|---|---|---|---|---|---|---|
(µg/mL) | ||||||||
MIC | MBC | MIC | MBC | MIC | MBC | MIC | MFC | |
8 | 128 | >128 | 128 | >128 | 64 | >128 | 64 | 128 |
9 | 128 | >128 | 128 | >128 | 64 | >128 | 64 | 128 |
10 | 128 | >128 | 128 | >128 | 128 | >128 | 64 | 128 |
11 | 128 | >128 | 128 | >128 | >128 | >128 | 64 | 128 |
12 | 128 | >128 | 128 | 128 | 128 | >128 | 64 | 128 |
13 | 128 | >128 | 128 | >128 | 128 | >128 | 64 | 128 |
14 | 128 | 128 | 64 | 128 | 128 | >128 | 64 | 128 |
15 | 128 | 128 | 64 | 128 | 64 | >128 | 64 | 128 |
16 | 128 | >128 | 128 | >128 | 128 | >128 | 64 | 128 |
17 | 128 | >128 | 128 | >128 | 128 | >128 | 64 | 128 |
Compound | S. a. ATCC 6538 | S. a. ATCC 43300 | S. e. PCM 2118 | E. f. ATCC 11420 | E. c. ATCC 11229 | P. a. ATCC 15442 | P. v. NCTC 4635 | C. a. ATCC 10231 |
---|---|---|---|---|---|---|---|---|
MBC/MIC | MFC/MIC | |||||||
8 | >4 | >8 | 4 | >1 | >1 | >1 | >2 | 2 |
9 | >16 | >32 | 2 | >16 | >1 | >1 | >2 | 2 |
10 | 8 | 2 | 1 | 8 | >1 | >1 | >1 | 2 |
11 | >16 | >16 | >32 | >16 | >1 | >1 | >1 | 2 |
12 | 16 | >16 | 32 | >4 | >1 | 1 | >1 | 2 |
13 | >4 | >4 | >4 | >1 | >1 | >1 | >1 | 2 |
14 | 16 | 16 | 2 | >8 | 1 | 2 | >1 | 2 |
15 | 16 | 16 | 1 | >8 | 1 | 2 | >2 | 2 |
16 | >32 | >32 | 1 | >1 | >1 | >1 | >1 | 2 |
17 | >16 | >32 | >32 | >1 | >1 | >1 | >1 | 2 |
Strain | MIC | MBC | MIC | MBC |
---|---|---|---|---|
(µg/mL) | ||||
Compound 10 | Compound 16 | |||
MRSA: | ||||
S.aureus 50 | 4 | >128 | 4 | >128 |
S.aureus 51 | 4 | >128 | 4 | >128 |
S.aureus 52 | 4 | >128 | 4 | >128 |
S.aureus 53 | 4 | >128 | 8 | >128 |
S.aureus 54 | 4 | >128 | 8 | >128 |
MSSA: | ||||
S.aureus 55 | 4 | >128 | 4 | >128 |
S.aureus 56 | 4 | >128 | 4 | >128 |
S.aureus 57 | 4 | >128 | 4 | >128 |
S.aureus 58 | 4 | >128 | 8 | >128 |
S.aureus 59 | 4 | >128 | 4 | >128 |
HaCaT | HaCaT | HCT-116 | HeLa | MCF-7 | |
---|---|---|---|---|---|
Compound | IC50 (μg/mL) | IC50 (μM) | IC50 (μM) | IC50 (μM) | IC50 (μM) |
8 | nt | nt | 91 ± 3 [16] | 95 ± 3 [16] | 170 ± 12 [16] |
9 | 40 ± 3 | 74 ± 5 | 78 ± 2 | 90 ± 4 | 65 ± 3 |
10 | 95 ± 4 | 178 ± 7 | 78 ± 3 | 94 ± 3 | 81 ± 3 |
11 | 42 ± 1 | 81 ± 2 | 66 ± 1 | 42 ± 2 | 82 ± 4 |
12 | 47 ± 2 | 92 ± 5 | 77 ± 3 | 88 ± 3 | 94 ± 3 |
14 | 147 ± 3 | 280 ± 6 | 81 ± 1 | 96 ± 5 | 73 ± 1 |
15 | 79 ± 3 | 150 ± 6 | 86 ± 2 | 165 ± 9 | 93 ± 3 |
16 | 19 ± 1 | 38 ± 2 | 77 ± 3 [16] | 43 ± 2 [16] | 96 ± 5 [16] |
17 | 49 ± 1 | 96 ± 2 | 79 ± 2 | 87 ± 3 | 92 ± 1 |
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Żołnowska, B.; Sławiński, J.; Garbacz, K.; Jarosiewicz, M.; Kawiak, A. N-(2-Arylmethylthio-4-Chloro-5-Methylbenzenesulfonyl)amide Derivatives as Potential Antimicrobial Agents—Synthesis and Biological Studies. Int. J. Mol. Sci. 2020, 21, 210. https://doi.org/10.3390/ijms21010210
Żołnowska B, Sławiński J, Garbacz K, Jarosiewicz M, Kawiak A. N-(2-Arylmethylthio-4-Chloro-5-Methylbenzenesulfonyl)amide Derivatives as Potential Antimicrobial Agents—Synthesis and Biological Studies. International Journal of Molecular Sciences. 2020; 21(1):210. https://doi.org/10.3390/ijms21010210
Chicago/Turabian StyleŻołnowska, Beata, Jarosław Sławiński, Katarzyna Garbacz, Małgorzata Jarosiewicz, and Anna Kawiak. 2020. "N-(2-Arylmethylthio-4-Chloro-5-Methylbenzenesulfonyl)amide Derivatives as Potential Antimicrobial Agents—Synthesis and Biological Studies" International Journal of Molecular Sciences 21, no. 1: 210. https://doi.org/10.3390/ijms21010210