Green Ultrasound versus Conventional Synthesis and Characterization of Specific Task Pyridinium Ionic Liquid Hydrazones Tethering Fluorinated Counter Anions: Novel Inhibitors of Fungal Ergosterol Biosynthesis
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Antifungal Screening
2.2.1. Determination of MIC90
2.2.2. Effect of the Synthesized Compounds on Membrane Ergosterol Content
2.2.3. Confocal Scanning Laser Microscopy (CSLM)
3. Experimental Section
3.1. Chemistry
3.2. General Alkylation Procedure for the Synthesis of Halogenated Specific Task ILs Tagged Hydrazones 2–7
3.2.1. Conventional Method (CM)
3.2.2. Ultrasound Method (US)
3.3. General Metathesis Procedure for the Synthesis of Fluorinated Specific Task ILs 8–25
3.3.1. Conventional Method (CM)
3.3.2. Ultrasound Method (US)
3.4. Antifungal Screening
3.4.1. Growth Conditions, Species Identification and Determination of MIC90
3.4.2. Ergosterol Extraction and Estimation Assay
3.4.3. Confocal Scanning Laser Microscopy (CSLM)
4. Conclusions
Supplementary Materials
Supplementary File 1Author Contributions
Conflicts of Interest
References
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Sample Availability: Not available. |
Compound No. | R | Conventional Method CM | Ultrasound Method US | ||
---|---|---|---|---|---|
Time (h) | Yield (%) | Time (h) | Yield (%) | ||
2 | CH2COOEt | 20 | 90 | 4 | 94 |
3 | p-ClC6H4COCH2 | 24 | 91 | 5 | 94 |
4 | p-NO2C6H4COCH2 | 24 | 80 | 5 | 88 |
5 | C6H5O(CH2)4 | 24 | 93 | 4 | 96 |
6 | C6H5CH2 | 40 | 89 | 6 | 92 |
7 | OH(CH2)2 | 48 | 80 | 6 | 88 |
Compound No. | R | Y | Conventional Method CM | Ultrasound Method US | ||
---|---|---|---|---|---|---|
Time (h) | Yield (%) | Time (h) | Yield (%) | |||
8 | CH2COOEt | PF6 | 16 | 88 | 4 | 92 |
9 | CH2COOEt | BF4 | 16 | 85 | 4 | 90 |
10 | CH2COOEt | COOCF3 | 16 | 83 | 4 | 90 |
11 | p-ClC6H4COCH2 | PF6 | 16 | 90 | 4 | 94 |
12 | p-ClC6H4COCH2 | BF4 | 16 | 86 | 4 | 90 |
13 | p-ClC6H4COCH2 | COOCF3 | 16 | 92 | 4 | 96 |
14 | p-NO2C6H4COCH2 | PF6 | 16 | 89 | 4 | 92 |
15 | p-NO2C6H4COCH2 | BF4 | 16 | 84 | 4 | 92 |
16 | p-NO2C6H4COCH2 | COOCF3 | 16 | 91 | 4 | 94 |
17 | C6H5O(CH2)4 | PF6 | 16 | 84 | 5 | 92 |
18 | C6H5O(CH2)4 | BF4 | 16 | 84 | 5 | 90 |
19 | C6H5O(CH2)4 | COOCF3 | 16 | 89 | 5 | 92 |
20 | C6H5CH2 | PF6 | 16 | 94 | 5 | 96 |
21 | C6H5CH2 | BF4 | 16 | 88 | 5 | 92 |
22 | C6H5CH2 | COOCF3 | 16 | 86 | 5 | 90 |
23 | OH(CH2)2 | PF6 | 16 | 90 | 5 | 94 |
24 | OH(CH2)2 | BF4 | 16 | 83 | 5 | 90 |
25 | OH(CH2)2 | COOCF3 | 16 | 87 | 5 | 92 |
Isolates/Strain | Species (Number of Strains) |
---|---|
Sensitive (standard, n = 4) | |
ATCC 10261 | C. albicans |
ATCC 90030 | C. glabrata |
ATCC 750 | C. tropicalis |
ATCC 6258 | C. krusei |
Clinical isolates (n = 36) | C. albicans (19), C. tropicalis (5), C. glabrata (8), C. krusei (4) |
Test Agents | MIC90 Range (μg/mL) |
---|---|
2 | >1000 |
3 | >1000 |
4 | >1000 |
5 | >1000 |
6 | >1000 |
7 | 500–1000 |
8 | 62.5–250 |
9 | 250–500 |
10 | 250–500 |
11 | 31.25–62.5 |
12 | 125–250 |
13 | 250–500 |
14 | 62.5–125 |
15 | 250–500 |
16 | 500–1000 |
17 | 125–250 |
18 | 250–500 |
19 | 500–1000 |
20 | 125–250 |
21 | 250–500 |
22 | 500–1000 |
23 | 250–500 |
24 | 500–1000 |
25 | 250–500 |
Fluconazole (standard drug) | 1–32 |
% Ergosterol Decrease | ||||
---|---|---|---|---|
Test Compound | Concentration | Standard Strains (n = 3) | Clinical Strains (n = 3) | |
Control | 0 | 0 | ||
8 | MIC/4 | 11.6 (± 0.69) | 12.9 (± 1.15) | |
MIC/2 | 38.3 (± 3.05) | 36.73 (± 2.61) | ||
MIC | 59.06 (± 4.10) | 55.23 (± 2.92) | ||
11 | MIC/4 | 52.43 (± 3.89) | 53.91 (± 3.26) | |
MIC/2 | 65.66 (± 4.93) | 62.76 (± 4.27) | ||
MIC | 88.26 (± 2.12) | 84.3 (± 5.00) | ||
14 | MIC/4 | 36.13 (± 4.00) | 29.26 (± 1.16) | |
MIC/2 | 51.16 (± 2.36) | 45.72 (± 1.83) | ||
MIC | 70.4 (± 2.62) | 71.41 (± 3.16) |
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Rezki, N.; Al-Sodies, S.A.; Shreaz, S.; Shiekh, R.A.; Messali, M.; Raja, V.; Aouad, M.R. Green Ultrasound versus Conventional Synthesis and Characterization of Specific Task Pyridinium Ionic Liquid Hydrazones Tethering Fluorinated Counter Anions: Novel Inhibitors of Fungal Ergosterol Biosynthesis. Molecules 2017, 22, 1532. https://doi.org/10.3390/molecules22111532
Rezki N, Al-Sodies SA, Shreaz S, Shiekh RA, Messali M, Raja V, Aouad MR. Green Ultrasound versus Conventional Synthesis and Characterization of Specific Task Pyridinium Ionic Liquid Hydrazones Tethering Fluorinated Counter Anions: Novel Inhibitors of Fungal Ergosterol Biosynthesis. Molecules. 2017; 22(11):1532. https://doi.org/10.3390/molecules22111532
Chicago/Turabian StyleRezki, Nadjet, Salsabeel A. Al-Sodies, Sheikh Shreaz, Rayees Ahmad Shiekh, Mouslim Messali, Vaseem Raja, and Mohamed R. Aouad. 2017. "Green Ultrasound versus Conventional Synthesis and Characterization of Specific Task Pyridinium Ionic Liquid Hydrazones Tethering Fluorinated Counter Anions: Novel Inhibitors of Fungal Ergosterol Biosynthesis" Molecules 22, no. 11: 1532. https://doi.org/10.3390/molecules22111532