Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. In Vitro Antifungal Activity
2.3. Molecular Docking Study
3. Materials and Methods
3.1. General Information
3.2. Synthesis of Methyl-4-(Benzyloxy)benzoate (3)
3.3. Synthesis of 4-(Benzyloxy)benzohydrazide (4)
3.4. Synthesis of 5-(4-(Benzyloxy)phenyl)-1,3,4-oxadiazole-2(3H)-thione
3.5. General Procedure for the Synthesis of 5-(4-(Benzyloxy)substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones 6a–o
3.6. Antifungal Screening
3.7. Molecular Docking Data
4. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Entry | Conventional | Ultrasonic Irradiation | ||
---|---|---|---|---|
Time (h) | Yield (%) | Time (h) | Yield (%) | |
6a | 15 | 68 | 1.5 | 80 |
6b | 16 | 63 | 1.0 | 81 |
6c | 15 | 62 | 1.5 | 78 |
6d | 17 | 58 | 2.0 | 79 |
6e | 18 | 45 | 1.0 | 81 |
6f | 18 | 56 | 1.0 | 79 |
6g | 19 | 57 | 2.0 | 81 |
6h | 17 | 61 | 1.5 | 90 |
6i | 18 | 53 | 1.0 | 82 |
6j | 17 | 63 | 1.5 | 85 |
6k | 15 | 58 | 1.5 | 80 |
6l | 17 | 57 | 1.0 | 81 |
6m | 15 | 61 | 2.0 | 79 |
6n | 16 | 58 | 2.0 | 79 |
6o | 15 | 45 | 2.0 | 78 |
Compound | Candida albicans ATCC 24433 | Candida albicans ATCC 10231 | Candida glabrata NCYC 388 | Cryptococcus neoformans ATCC 34664 | Cryptococcus neoformans PRL 518 | Aspergillus fumigatus NCIM 902 | Aspergillus niger ATCC 10578 |
---|---|---|---|---|---|---|---|
6a | 64 | 49.6 | 64 | 64 | 64 | >256 | 27.7 |
6b | 128 | 67.12 | 59.6 | 77.5 | >128 | 24.2 | 24.1 |
6c | 21.6 | 108 | 53.6 | 108.9 | 196.5 | 11.2 | 93 |
6d | 68 | 159 | 65.6 | 128 | >128 | 6 | 130 |
6e | 54.4 | 44.6 | 24.5 | 64 | 14.21 | 25.8 | 47 |
6f | 16 | 84.9 | 5.4 | >256 | 90 | 256 | 256 |
6g | 62 | 107.6 | 256 | 76.8 | 94.7 | 4 | >256 |
6h | 55.3 | 57.4 | 64 | 47.6 | 66.6 | 16 | 18.61 |
6i | 23.3 | 80.6 | 40.3 | 256 | 93.5 | 24.6 | >256 |
6j | 38.4 | 31.5 | 56.6 | 192 | 39 | 8 | 128 |
6k | 150 | 53.3 | 36.2 | 64.2 | 146.6 | 35.1 | 22.9 |
6l | 115 | 95.3 | 42.5 | 49.7 | 145.8 | 81 | 73.2 |
6m | 91.5 | 49.7 | 78.6 | 62.5 | 54.6 | 87.4 | 84.8 |
6n | 30.3 | 43 | 48.8 | 47.5 | 105.6 | 81.5 | 56.9 |
6o | 95 | 28.1 | 50.7 | 42.7 | 156.5 | 76.1 | 70.5 |
Fluconazole | 0.12 | 0.11 | 9.4 | 16 | 4 | 64 | 46 |
Compound | Binding Energy | Hydrogen Bonds | Hydrophobic Bonds |
---|---|---|---|
6a | −41.69 | LEU412-O=C | ALA343, GLY344, LEU412, MET415, PHE499, GLY508 and ALA512 |
6b | −49.33 | LEU412-O=C | ALA343, THR347, MET415, GLY500 and HIS504 |
6c | −57.85 | CYS506-O-CH2 | LEU412, SER414, MET415, CYC506, ILE507 and GLY508 |
6d | −45.23 | CYS506-O-CH2 | ALA343, LEU412, MET415, CYC506, ILE507 and GLY508 |
6e | −35.50 | LEU412-O=C; GLY500-N of nitro and GLY500-O-N of NO2 | ALA343, LEU412, ILE507 and GLY508 |
6f | −65.25 | CYS506-NH | ALA343, THR347, MET415, PHE499, HIS504, CYC506, GLY508, GLU509, ALA512 and TYR513 |
6g | −52.37 | LEU412-O=C | THR347, LEU412, MET415, PHE499 and HIS504 |
6h | −47.18 | VAL497 and GLY500-N of NO2 | ALA343, GLY344, PHE499, GLY500 and GLY508 |
6i | −61.03 | TYR154-O-N of 2-nitro; TYR168- O=C and MET415-N of 4-nitro | LEU340 and ALA343 |
6j | −40.29 | LEU412-O-CH2 | ALA343, GLY344, LEU412, MET415, PHE499, GLY508 and ALA512 |
6k | −37.85 | - | ALA343, GLY344, THR347, PHE499, GLY500 and GLY508 |
6l | −42.91 | - | LEU186, LEU240, GLY344, THR347, MET415, PHE499, GLY500, CYS506, GLY508 and PHE511 |
6m | −36.83 | - | ALA343, LEU412 and PHE499 |
6n | −40.09 | CYS506-O-CH2 | ALA343, VAL440, PRO442, VAL497, GLY500 and CYC506 |
6o | −38.97 | TYR168-O=C | LEU340, ALA343, ILE507 and GLY508 |
Fluconazole | −67.29 | TYR168-F of phenyl | GLY500 and HIS504 |
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Nimbalkar, U.D.; Tupe, S.G.; Seijas Vazquez, J.A.; Khan, F.A.K.; Sangshetti, J.N.; Nikalje, A.P.G. Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones. Molecules 2016, 21, 484. https://doi.org/10.3390/molecules21050484
Nimbalkar UD, Tupe SG, Seijas Vazquez JA, Khan FAK, Sangshetti JN, Nikalje APG. Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones. Molecules. 2016; 21(5):484. https://doi.org/10.3390/molecules21050484
Chicago/Turabian StyleNimbalkar, Urja D., Santosh G. Tupe, Julio A. Seijas Vazquez, Firoz A. Kalam Khan, Jaiprakash N. Sangshetti, and Anna Pratima G. Nikalje. 2016. "Ultrasound- and Molecular Sieves-Assisted Synthesis, Molecular Docking and Antifungal Evaluation of 5-(4-(Benzyloxy)-substituted phenyl)-3-((phenylamino)methyl)-1,3,4-oxadiazole-2(3H)-thiones" Molecules 21, no. 5: 484. https://doi.org/10.3390/molecules21050484