Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Toxicity Prediction
2.3. Prediction of Activity Spectra of Compounds by Program PASS
2.4. Biological Evaluation
2.5. Antifungal Activity
2.6. In Silico Predictive Studies (Molecular Properties and Drug-Likeness)
2.7. Docking Studies
Docking Studies to Antibacterial Targets
3. Materials and Methods
3.1. Chemistry
- Synthesis of 2-(2-(4-nitrophenyl)-4-oxothiazolidin-3-yl)benzo[d]thiazole-6-carbonitrile (1).
- Synthesis of 2-(2-(2,6-difluorophenyl)-4-oxothiazolidin-3-yl)benzo[d]thiazole-6-carbonitrile (2).
- Synthesis of 2-(2-(2-chloro-6-fluorophenyl)-4-oxothiazolidin-3-yl)benzo[d]thiazole-6-carbonitrile (3).
- Synthesis of 2-(2-(2,6-dichlorophenyl)-4-oxothiazolidin-3-yl)benzo[d]thiazole-6-carbonitrile (4).
- Synthesis of 2-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)benzo[d]thiazole-6-carbonitrile (5).
- Synthesis of 3-(6-(adamantan-1-yl)benzo[d]thiazol-2-yl)-2-(2,6-dichlorophenyl)thiazolidin-4-one (6).
- Synthesis of 3-(6-(adamantan-1-yl)benzo[d]thiazol-2-yl)-2-(2-chloro-6-fluorophenyl) thiazolidin-4-one (7).
- Synthesis of 3-(6-(adamantan-1-yl)-4-methylbenzo[d]thiazol-2-yl)-2-(2,6-dichlorophenyl)thiazolidin-4-one (8).
- Synthesis of 3-(6-(adamantan-1-yl)-4-methylbenzo[d]thiazol-2-yl)-2-(2,6-difluorophenyl)thiazolidin-4-one (9).
- Synthesis of 2-(4-fluorophenyl) -3-(4-methoxybenzo [d] thiazol-2-yl) thiazolidin-4-one (10).
- Synthesis of 3-(4-methoxybenzo[d]thiazol-2-yl)-2-(4-nitrophenyl)thiazolidin-4-one (11).
- Synthesis of 2-(4-chlorophenyl)-3-(4-methoxybenzo[d]thiazol-2-yl)thiazolidin-4-one (12).
- Synthesis of 3-(4-methoxybenzo[d]thiazol-2-yl)-2-(4-methoxyphenyl)thiazolidin-4-one (13).
- Synthesis of 2-(4-hydroxyphenyl)-3-(4-methoxybenzo[d]thiazol-2-yl)thiazolidin-4-one (14).
- Synthesis of 3-(6-chlorobenzo[d]thiazol-2-yl)-2-(4-fluorophenyl)thiazolidin-4-one (15).
- Synthesis of 3-(6-chlorobenzo[d]thiazol-2-yl)-2-(4-nitrophenyl)thiazolidin-4-one (16).
- Synthesis of 3-(6-chlorobenzo[d]thiazol-2-yl)-2-(4-chlorophenyl)thiazolidin-4-one (17).
- Synthesis of 3-(6-chlorobenzo[d]thiazol-2-yl)-2-(4-methoxyphenyl)thiazolidin-4-one (18).
- Synthesis of (3-(6-chlorobenzo[d]thiazol-2-yl)-2-(4-hydroxyphenyl)thiazolidin-4-one (19).
3.2. Biological Evaluation
3.2.1. Antibacterial Action
E. coli
Pseudomonas aeruginosa
3.2.2. Inhibition of Biofilm Formation
3.2.3. Antifungal Activity
3.3. Statistical Analysis
3.4. Drug-Likeness
3.5. Docking Studies
4. 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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No. | Predicted LD50 | Predicted Toxicity Class | Hepatotoxicity | Carcinogenicity | Immunotoxicity | Mutagenicity | Cytotoxicity |
---|---|---|---|---|---|---|---|
1 | 500 mg/kg | 4 | Inactive 0.54 | Inactive 0.57 | Inactive 0.99 | Inactive 0.67 | Inactive 0.76 |
2 | 1000 mg/kg | 4 | Inactive 0.52 | Inactive 0.63 | Inactive 0.97 | Inactive 0.66 | Inactive 0.62 |
3 | 500 mg/kg | 4 | Inactive 0.56 | Inactive 0.65 | Inactive 0.99 | Inactive 0.67 | Inactive 0.78 |
4 | 500 mg/kg | 4 | Inactive 0.54 | Inactive 0.57 | Inactive 0.99 | Inactive 0.67 | Inactive 0.76 |
5 | 500 mg/kg | 4 | Inactive 0.58 | Inactive 0.56 | Inactive 0.99 | Inactive 0.66 | Inactive 0.77 |
6 | 500 mg/kg | 4 | Inactive 0.50 | Inactive 0.55 | Inactive 0.94 | Inactive 0.64 | Inactive 0.75 |
7 | 500 mg/kg | 4 | Inactive 0.52 | Inactive 0.55 | Inactive 0.79 | Inactive 0.64 | Inactive 0.74 |
8 | 500 mg/kg | 4 | Inactive 0.52 | Inactive 0.56 | Inactive 0.96 | Inactive 0.63 | Inactive 0.75 |
9 | 500 mg/kg | 4 | Inactive 0.54 | Inactive 0.56 | Inactive 0.94 | Inactive 0.63 | Inactive 0.77 |
10 | 500 mg/kg | 4 | Inactive 0.50 | Inactive 0.62 | Inactive 0.98 | Inactive 0.61 | Inactive 0.63 |
11 | 500 mg/kg | 4 | Inactive 0.52 | Inactive 0.64 | Inactive 0.99 | Inactive 0.60 | Inactive 0.63 |
12 | 500 mg/kg | 4 | Inactive 0.59 | Inactive 0.60 | Inactive 0.98 | Inactive 0.66 | Inactive 0.66 |
13 | 1000 mg/kg | 4 | Inactive 0.52 | Inactive 0.65 | Inactive 0.99 | Inactive 0.66 | Inactive 0.74 |
14 | 500 mg/kg | 4 | Inactive 0.56 | Inactive 0.60 | Inactive 0.98 | Inactive 0.67 | Inactive 0.65 |
15 | 500 mg/kg | 4 | Inactive 0.57 | Inactive 0.55 | Inactive 0.99 | Inactive 0.67 | Inactive 0.81 |
16 | 500 mg/kg | 4 | Inactive 0.60 | Inactive 0.58 | Inactive 0.99 | Inactive 0.68 | Inactive 0.68 |
17 | 500 mg/kg | 4 | Inactive 0.57 | Inactive 0.55 | Inactive 0.99 | Inactive 0.67 | Inactive 0.81 |
18 | 1000 mg/kg | 4 | Inactive 0.52 | Inactive 0.65 | Inactive 0.99 | Active 0.91 | Inactive 0.74 |
19 | 500 mg/kg | 4 | Inactive 0.54 | Inactive 0.55 | Inactive 0.99 | Inactive 0.68 | Inactive 0.82 |
N | Carcinogenicity (Rodents (Multiple Species/Sites)) | Carcinogenicity (Rat) | Carcinogenicity (Mouse) | Mutagenicity (Salmonella typhimurium) |
---|---|---|---|---|
1 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 |
2 | Inactive Conf.: 0.027 | Inactive Conf.: 0.027 | Inactive Conf.: 0.026 | Inactive Conf.: 0.027 |
3 | Inactive Conf.: 0.024 | Inactive Conf.: 0.027 | Inactive Conf.: 0.033 | Inactive Conf.: 0.036 |
4 | Inactive Conf.: 0.031 | Inactive Conf.: 0.028 | Inactive Conf.: 0.041 | Inactive Conf.: 0.028 |
5 | Inactive Conf.: 0.028 | Inactive Conf.: 0.028 | Inactive Conf.: 0.041 | Inactive Conf.: 0.026 |
6 | Inactive Conf.: 0.026 | Inactive Conf.: 0.027 | Inactive Conf.: 0.029 | Inactive Conf.: 0.026 |
7 | Inactive Conf.: 0.031 | Inactive Conf.: 0.027 | Inactive Conf.: 0.031 | Inactive Conf.: 0.028 |
8 | Inactive Conf.: 0.025 | Inactive Conf.: 0.028 | Inactive Conf.: 0.027 | Inactive Conf.: 0.028 |
9 | Inactive Conf.: 0.028 | Inactive Conf.: 0.026 | Inactive Conf.: 0.049 | Inactive Conf.: 0.041 |
10 | Inactive Conf.: 0.033 | Inactive Conf.: 0.028 | Inactive Conf.: 0.041 | Inactive Conf.: 0.031 |
11 | Inactive Conf.: 0.032 | Inactive Conf.: 0.026 | Inactive Conf.: 0.041 | Inactive Conf.: 0.033 |
12 | Inactive Conf.: 0.028 | Inactive Conf.: 0.029 | Inactive Conf.: 0.028 | Inactive Conf.: 0.028 |
13 | Inactive Conf.: 0.031 | Inactive Conf.: 0.028 | Inactive Conf.: 0.041 | Inactive Conf.: 0.039 |
14 | Inactive Conf.: 0.034 | Inactive Conf.: 0.028 | Inactive Conf.: 0.041 | Inactive Conf.: 0.038 |
15 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 | Inactive Conf.: 0.028 |
16 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 | Inactive Conf.: 0.026 |
17 | Inactive Conf.: 0.028 | Inactive Conf.: 0.028 | Inactive Conf.: 0.029 | Inactive Conf.: 0.027 |
18 | Inactive Conf.: 0.026 | Inactive Conf.: 0.027 | Inactive Conf.: 0.033 | Inactive Conf.: 0.035 |
19 | Inactive Conf.: 0.033 | Inactive Conf.: 0.027 | Inactive Conf.: 0.041 | Inactive Conf.: 0.027 |
Compounds | S.a. | MRSA | L.m. | P.a. | P.a. Res | E. coli | E. coli Res | S. ty. | |
---|---|---|---|---|---|---|---|---|---|
1 | MIC | 0.30 ± 0.07 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.11 | 0.12 ± 0.00 | 0.25 ± 0.11 | 0.50 ± 0.00 |
MBC | 0.50 ± 0.00 | 1.00 ± 0.00 | 0.83 ± 0.11 | 0.58 ± 0.11 | 0.50 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 | 0.75 ± 0.05 | |
2 | MIC | 0.12 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.30 ± 0.07 | 0.25 ± 0.04 | 0.12 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.04 |
MBC | 0.25 ± 0.00 | 0.50 ± 0.00 | 0.75 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | |
3 | MIC | 0.50 ± 0.00 | 0.30 ± 0.07 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.20 ± 0.01 | 0.20 ± 0.00 | 0.25 ± 0.00 | 0.30 ± 0.07 |
MBC | 1.00 ± 0.00 | 0.50 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.25 ± 0.04 | 0.50 ± 0.00 | 0.50 ± 0.00 | |
4 | MIC | 0.25 ± 0.04 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.20 ± 0.01 | 0.10 ± 0.00 | 0.25 ± 0.04 | 0.25 ± 0.00 |
MBC | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.12 ± 0.00 | 0.50 ± 0.00 | 0.83 ± 0.11 | |
5 | MIC | 0.25 ± 0.00 | 0.30 ± 0.07 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 |
MBC | 0.50 ± 0.00 | 0.50 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 | 1.00 ± 0.00 | |
6 | MIC | 0.12 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.04 | 0.20 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 |
MBC | 0.25 ± 0.04 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.83 ± 0.11 | |
7 | MIC | 0.20 ± 0.00 | 0.50 ± 0.00 | 0.75 ± 0.00 | 0.25 ± 0.04 | 0.25 ± 0.00 | 0.20 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 |
MBC | 0.25 ± 0.04 | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.58 ± 0.11 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.50 ± 0.00 | 0.83 ± 0.11 | |
8 | MIC | 0.20 ± 0.00 | 0.50 ± 0.00 | 0.30 ± 0.07 | 0.25 ± 0.00 | 0.06 ± 0.00 | 0.20 ± 0.00 | 0.25 ± 0.00 | 0.30 ± 0.07 |
MBC | 0.25 ± 0.04 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.004 | 0.50 ± 0.00 | 0.50 ± 0.00 | |
9 | MIC | 0.12 ± 0.00 | 0.58 ± 0.11 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.30 ± 0.07 | 0.20 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 |
MBC | 0.25 ± 0.04 | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.50 ± 0.00 | 1.00 ± 0.00 | |
Streptomycin | MIC | 0.10 ± 0.00 | 0.10 ± 0.00 | 0.15 ± 0.00 | 0.10 ± 0.00 | 0.05 ± 0.00 | 0.10 ± 0.00 | 0.10 ± 0.00 | 0.10 ± 0.00 |
MBC | 0.20 ± 0.01 | 0.30 ± 0.01 | 0.20 ± 0.01 | 0.10 ± 0.00 | 0.20 ± 0.00 | 0.20 ± 0.01 | 0.20 ± 0.01 | ||
Ampicillin | MIC | 0.10 ± 0.00 | 0.15 ± 0.00 | 0.30 ± 0.01 | 0.2 ± 0.01 | 0.15 ± 0.00 | 0.20 ± 0.01 | 0.10 ± 0.00 | |
MBC | 0.15 ± 0.00 | 0.30 ± 0.02 | 0.50 ± 0,01 | 0.20 ± 0.01 | 0.20 ± 0.00 |
Compounds | S.a. | MRSA | L.m. | P.a. | P.a. Res | E. coli | E. coli Res | S. ty. | |
---|---|---|---|---|---|---|---|---|---|
10 | MIC | 0.50 ± 0.00 | 0.75 ± 0.00 | 0.75 ± 0.02 | 0.20 ± 0.00 | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.50 ± 0.03 | 0.50 ± 0.02 |
MBC | 1.00 ± 0.08 | 1.00 ± 0.00 | >1.00 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.25 ± 0.00 | 1.00 ± 0.04 | 1.00 ± 0.04 | |
11 | MIC | 0.50 ± 0.02 | 0.75 ± 0.03 | 0.50 ± 0.02 | 0.25 ± 0.00 | 0.15 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.03 | 0.50 ± 0.02 |
MBC | 0.75 ± 0.04 | 1.00 ± 0.06 | 1.00 ± 0.06 | 0.50 ± 0.03 | 0.25 ± 0.01 | 0.50 ± 0.03 | 0.75 ± 0.02 | 1.00 ± 0.04 | |
12 | MIC | 0.50 ± 0.02 | 0.75 ± 0.03 | 0.50 ± 0.03 | 0.25 ± 0.01 | 0.25 ± 0.00 | 0.25 ± 0.01 | 0.50 ± 0.03 | 0.50 ± 0.01 |
MBC | 1.00 ± 0.06 | >1.00 | >1.00 | 0.50 ± 0.03 | 0.50 ± 0.02 | 0.50 ± 0.02 | 1.00 ± 0.08 | 1.00 ± 0.06 | |
13 | MIC | 0.50 ± 0.02 | 0.25 ± 0.00 | 0.75 ± 0.04 | 0.30 ± 0.01 | 0.15 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.03 |
MBC | 0.75 ± 0.04 | 0.50 ± 0.00 | 1.00 ± 0.08 | 0.50 ± 0.02 | 0.25 ± 0.01 | 0.25 ± 0.01 | 0.50 ± 0.03 | 1.00 ± 0.04 | |
14 | MIC | 0.25 ± 0.01 | 0.75 ± 0.03 | 0.50 ± 0.02 | 0.25 ± 0.01 | 0.15 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.00 | 0.12 ± 0.00 |
MBC | 0.50 ± 0.02 | 1.00 ± 0.06 | 1.00 ± 0.08 | 0.50 ± 0.03 | 0.25 ± 0.01 | 0.25 ± 0.01 | 0.50 ± 0.03 | 0.50 ± 0.02 | |
15 | MIC | 0.30 ± 0.01 | 0.50 ± 0.03 | 0.25 ± 0.01 | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.01 | 0.25 ± 0.00 | 0.50 ± 0.03 |
MBC | 0.50 ± 0.03 | 0.75 ± 0.00 | 0.50 ± 0.03 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.00 | 0.75 ± 0.03 | |
16 | MIC | 0.10 ± 0.00 | 0.10 ± 0.00 | 0.06 ± 0.00 | 0.30 ± 0.00 | 0.25 ± 0.01 | 0.30 ± 0.01 | 0.12 ± 0.00 | 0.10 ± 0.00 |
MBC | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.60 ± 0.00 | 0.50 ± 0.03 | 0.60 ± 0.03 | 0.25 ± 0.00 | 0.12 ± 0.00 | |
17 | MIC | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.25 ± 0.00 | 0.12 ± 0.00 | 0.10 ± 0.00 | 0.25 ± 0.01 | 0.25 ± 0.00 | 0.30 ± 0.00 |
MBC | 0.75 ± 0.03 | 0.75 ± 0.04 | 0.50 ± 0.02 | 0.25 ± 0.01 | 0.12 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.03 | 0.50 ± 0.03 | |
18 | MIC | 0.20 ± 0.00 | 0.20 ± 0.00 | 0.12 ± 0.00 | 0.10 ± 0.00 | 0.06 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.01 | 0.25 ± 0.00 |
MBC | 0.25 ± 0.01 | 0.25 ± 0.00 | 0.20 ± 0.00 | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.20 ± 0.01 | 0.50 ± 0.02 | 0.50 ± 0.02 | |
19 | MIC | 0.25 ± 0.01 | 0.25 ± 0.00 | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.10 ± 0.00 | 0.12 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.00 |
MBC | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.12 ± 0.00 | 0.25 ± 0.01 | 0.25 ± 0.00 | 0.50 ± 0.02 | |
Streptomycin | MIC | 0.10 ± 0.00 | 0.10 ± 0.00 | 0.15 ± 0.00 | 0.10 ± 0.00 | 0.05 ± 0.00 | 0.10 ± 0.00 | 0.10 ± 0.00 | 0.10 ± 0.00 |
MBC | 0.20 ± 0.01 | 0.30 ± 0.01 | 0.20 ± 0.01 | 0.10 ± 0.00 | 0.20 ± 0.00 | 0.20 ± 0.01 | 0.20 ± 0.01 | ||
Ampicillin | MIC | 0.10 ± 0.00 | 0.15 ± 0.00 | 0.30 ± 0.01 | 0.2 ± 0.01 | 0.15 ± 0.00 | 0.20 ± 0.01 | 0.10 ± 0.00 | |
MBC | 0.15 ± 0.00 | 0.30 ± 0.02 | 0.50 ± 0,01 | 0.20 ± 0.01 | 0.20 ± 0.00 |
Compound | MIC | 0.5 MIC |
---|---|---|
16 | 49.46 ± 5.67 | 35.55 ± 2.30 |
18 | NE | NE |
19 | 51.46 ± 8.76 | 41.76 ± 9.99 |
8 | NE | NE |
Ampicillin | 70.00 ± 10.23 | 52.36 ± 3.67 |
Streptomycin | 63.56 ± 8.28 | 29.12 ± 1.22 |
Compounds | A.f. | A.n. | A.v. | P.f. | T.v. | P.v.c. | |
---|---|---|---|---|---|---|---|
1 | MIC | >1.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.00 | 0.50 ± 0.02 |
MFC | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
2 | MIC | >1.00 | 0.50 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 1.00 ± 0.00 |
MFC | >1.00 | 1.00 ± 0.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | >1.00 | |
3 | MIC | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.00 |
MFC | >1.00 | >1.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
4 | MIC | 1.00 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.50 ± 0.02 | 1.00 ± 0.00 | >1.00 |
MFC | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | >1.00 | >1.00 | |
5 | MIC | >1.00 | >1.00 | >1.00 | >1.00 | >1.00 | >1.00 |
MFC | >1.00 | >1.00 | >1.00 | >1.00 | >1.00 | >1.00 | |
6 | MIC | >1.00 | >1.00 | 0.25 ± 0.00 | 0.25 ± 0.04 | 0.25 ± 0.04 | 0.25 ± 0.04 |
MFC | >1.00 | >1.00 | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.50 ± 0.02 | |
7 | MIC | 0.50 ± 0.00 | 1.00 ± 0.00 | 0.25 ± 0.04 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 |
MFC | 1.00 ± 0.00 | >1.00 | 0.50 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
8 | MIC | >1.00 | >1.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.00 |
MFC | >1.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
9 | MIC | 0.50 ± 0.02 | 1.00 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 | 0.25 ± 0.00 | 0.50 ± 0.00 |
MFC | 1.00 ± 0.00 | >1.00 | 0.50 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.83 ± 0.11 | |
10 | MIC | 0.50 ± 0.02 | 1.00 ± 0.00 | 0.25 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.02 |
MBC | 1.00 ± 0.00 | >1.00 | 0.50 ± 0.03 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
11 | MIC | 1.00 ± 0.00 | >1.00 | 0.50 ± 0.01 | 0.50 ± 0.03 | 0.25 ± 0.00 | 0.50 ± 0.00 |
MBC | >1.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.02 | 1.00 ± 0.00 | |
12 | MIC | 0.50 ± 0.02 | 1.00 ± 0.00 | 0.50 ± 0.02 | 1.00 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.02 |
MBC | 1.00 ± 0.00 | >1.00 | 1.00 ± 0.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
13 | MIC | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.50 ± 0.03 | 0.50 ± 0.03 |
MBC | >1.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
14 | MIC | 1.00 ± 0.00 | 0.50 ± 0.03 | 0.25 ± 0.00 | 0.50 ± 0.03 | 0.50 ± 0.03 | 0.50 ± 0.02 |
MBC | >1.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | |
15 | MIC | 1.00 ± 0.00 | >1.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.02 | 0.25 ± 0.00 |
MBC | >1.00 | >1.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.02 | |
16 | MIC | 0.12 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.02 | 1.00 ± 0.00 |
MBC | 0.25 ± 0.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | >1.00 | |
17 | MIC | 1.00 ± 0.00 | >1.00 | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.25 ± 0.00 | 0.25 ± 0.00 |
MBC | >1.00 | >1.00 | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.00 | |
18 | MIC | 0.50 ± 0.01 | 0.50 ± 0.02 | 0.12 ± 0.00 | 0.50 ± 0.02 | 0.25 ± 0.00 | 0.25 ± 0.04 |
MBC | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.25 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.02 | |
19 | MIC | 0.50 ± 0.03 | 0.50 ± 0.00 | 0.25 ± 0.04 | 0.25 ± 0.00 | 0.25 ± 0.00 | 0.12 ± 0.00 |
MBC | 1.00 ± 0.00 | 1.00 ± 0.00 | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.50 ± 0.02 | 0.25 ± 0.01 | |
Bifonazole | MIC | 1.00 ± 0.00 | >1.00 | 1.00 ± 0.00 | 0.50 ± 0.00 | 0.50 ± 0.02 | 0.25 ± 0.00 |
MFC | 0.20 ± 0.000 | 0.20 ± 0.000 | 0.20 ± 0.01 | 0.25 ± 0.01 | 0.20 ± 0.01 | 0.20 ± 0.00 | |
Ketoconazole | MIC | 0.20 ± 0.01 | 0.20 ± 0.01 | 0.20 ± 0.00 | 0.20 ± 0.00 | 1.00 ± 0.01 | 0.20 ± 0.01 |
MFC | 0.50 ± 0.03 | 0.50 ± 0.03 | 0.50 ± 0.02 | 0.50 ± 0.03 | 1.50 ± 0.02 | 0.30 ± 0.01 |
No. | MW | Number of HBA a | Number of HBD b | Log Po/w c | Log S d | TPSA e | Absorption% f | Lipinski, Ghose, Veber, Egan, and Muegge Violations | Bioavailability Score | Drug-Likeness Model Score |
---|---|---|---|---|---|---|---|---|---|---|
1 | 382.42 | 5 | 0 | 2.09 | Moderately soluble | 156.35 | 68.9 | 0 | 0.55 | −0.45 |
2 | 373.4 | 5 | 0 | 2.7 | Poorly soluble | 110.53 | 55.1 | 0 | 0.55 | −0.49 |
3 | 389.85 | 4 | 0 | 2.79 | Poorly soluble | 110.53 | 70.9 | 0 | 0.55 | −0.42 |
4 | 406.31 | 3 | 0 | 2.87 | Poorly soluble | 110.53 | 70.9 | 0 | 0.55 | −0.39 |
5 | 355.41 | 4 | 0 | 2.62 | Moderately soluble | 110.53 | 70.9 | 0 | 0.55 | −0.07 |
6 | 515.52 | 2 | 0 | 4.3 | Poorly soluble | 86.74 | 79.1 | 2 | 0.17 | 0.22 |
7 | 499.06 | 3 | 0 | 4.24 | Poorly soluble | 86.74 | 79.1 | 1 | 0.55 | 0.2 |
8 | 529.54 | 2 | 0 | 4.55 | Poorly soluble | 86.74 | 79.1 | 2 | 0.17 | 0.56 |
9 | 496.63 | 4 | 0 | 4.34 | Poorly soluble | 86.74 | 79.1 | 1 | 0.55 | 0.45 |
10 | 360.43 | 4 | 0 | 3.02 | Moderately soluble | 95.97 | 76.4 | 0 | 0.55 | 0.28 |
11 | 387.43 | 5 | 0 | 2.49 | Moderately soluble | 141.79 | 59.1 | 0 | 0.55 | −0.17 |
12 | 376.88 | 3 | 0 | 3.1 | Poorly soluble | 95.97 | 76.4 | 0 | 0.55 | 0.39 |
13 | 372.46 | 4 | 0 | 3.45 | Moderately soluble | 105.2 | 72.7 | 0 | 0.55 | −0.06 |
14 | 358.43 | 4 | 1 | 2.56 | Moderately soluble | 116.2 | No | 0 | 0.55 | 0.13 |
15 | 364.84 | 3 | 0 | 3.25 | Poorly soluble | 86.74 | 79.1 | 0 | 0.55 | −0.08 |
16 | 391.85 | 4 | 0 | 2.38 | Moderately soluble | 132.56 | 63.3 | 0 | 0.55 | −0.13 |
17 | 381.3 | 2 | 0 | 3.42 | Poorly soluble | 86.74 | 79.1 | 0 | 0.55 | −0.08 |
18 | 376.88 | 3 | 0 | 3.37 | Poorly soluble | 95.97 | 76.4 | 0 | 0.55 | 0.18 |
19 | 362.85 | 3 | 1 | 2.73 | Moderately soluble | 106.97 | 72.1 | 0 | 0.55 | 0.1 |
No. | Drug-Likeness Model | No. | Drug-Likeness Model | No. | Drug-Likeness Model |
---|---|---|---|---|---|
1 | 8 | 14 | |||
2 | 9 | 15 | |||
3 | 10 | 16 | |||
4 | 11 | 17 | |||
5 | 12 | 18 | |||
6 | 13 | 19 | |||
7 |
No. | Est. Binding Energy (kcal/mol) | I-H LdcA | Residues Involved in H-Bond Formation LdcA | |||||
---|---|---|---|---|---|---|---|---|
E. coli Gyrase 1KZN | Thymidylate Kinase 4QGG | E. coli Primase 1DDE | E. coli MurB 2Q85 | E. coli LdcA 1ZRS (R+) | E. coli LdcA 1ZRS (S−) | |||
1 | -5.73(R+) | −2.41(S−) | −5.12(R+) | −5.81 | −4.63 | |||
2 | −5.01(S−) | −1.24(S−) | −1.88(R+) | −5.96(R+) | −7.53 | −7.23 | 2 | Tyr138, His285 |
3 | −4.12(R+) | −3.32(R+) | −5.23(S−) | −5.34 | −4.10 | |||
4 | −4.51(R+) | −4.14(S−) | −7.31 | −6.45 | 1 | Ser115, Tyr224 | ||
5 | −4.96(R+) | −1.53(S−) | −4.76(R+) | −5.52 | −5.14 | |||
6 | −3.41(R+) | −5.66(S−) | −7.10 | −6.80 | 2 | Ser115 | ||
7 | −4.40(R+) | −2.33(S−) | −4.71(R+) | −5.82 | −5.62 | |||
8 | −4.56(S−) | −1.95(S−) | −5.92(R+) | −7.80 | −7.53 | 1 | His285 | |
9 | −5.67(R+) | −6.11(R+) | −6.01 | −5.16 | ||||
10 | −3.35(S−) | −2.58(R+) | −4.22(S−) | −4.76 | −4.24 | |||
11 | −2.14(S−) | −1.28(S−) | −2.10(S−) | −3.01(S−) | −4.16 | −3.28 | ||
12 | −3.45(R+) | −3.61(S−) | −4.50 | −3.95 | ||||
13 | −4.55(R+) | −1.42(S−) | −3.34(R+) | −6.02 | −5.12 | 1 | Tyr138 | |
14 | −2.03(R+) | −1.22(S−) | −6.13 | −5.10 | 1 | Tyr224 | ||
15 | −5.01(R+) | −3.17(R+) | −2.99(R+) | −4.86(R+) | −6.14 | −6.11 | 1 | Tyr224 |
16 | −4.17(S−) | −1.09(R+) | −6.33(R+) | −8.63 | −7.58 | 2 | Ser115, Tyr224 | |
17 | −2.92(R+) | −4.18(S−) | −6.11 | −5.13 | 1 | Tyr224 | ||
18 | −5.21(S−) | −1.78(S−) | −2.86(R+) | −6.53(R+) | −8.52 | −7.64 | 1 | Ser115 |
19 | −4.69(R+) | −1.62(S−) | −6.71(R+) | −8.11 | −7.95 | 3 | Tyr138, His285, Gly286 |
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Haroun, M.; Tratrat, C.; Petrou, A.; Geronikaki, A.; Ivanov, M.; Ćirić, A.; Soković, M.; Nagaraja, S.; Venugopala, K.N.; Balachandran Nair, A.; et al. Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation. Molecules 2021, 26, 4061. https://doi.org/10.3390/molecules26134061
Haroun M, Tratrat C, Petrou A, Geronikaki A, Ivanov M, Ćirić A, Soković M, Nagaraja S, Venugopala KN, Balachandran Nair A, et al. Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation. Molecules. 2021; 26(13):4061. https://doi.org/10.3390/molecules26134061
Chicago/Turabian StyleHaroun, Michelyne, Christophe Tratrat, Anthi Petrou, Athina Geronikaki, Marija Ivanov, Ana Ćirić, Marina Soković, Sreeharsha Nagaraja, Katharigatta Narayanaswamy Venugopala, Anroop Balachandran Nair, and et al. 2021. "Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation" Molecules 26, no. 13: 4061. https://doi.org/10.3390/molecules26134061