Synthesis, Molecular Docking and Preliminary in-Vitro Cytotoxic Evaluation of Some Substituted Tetrahydro-naphthalene (2',3',4',6'-Tetra-O-Acetyl-β-D-Gluco/-Galactopyranosyl) Derivatives
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
Comp No. | Ar | R1 | R2 | MP (°C) | Cryst.Solv. | Yield % | Molecular Formula (Mol. Wt.) |
---|---|---|---|---|---|---|---|
2a | -C4H3O | --- | --- | 245–247 | Ethanol/H2O | 80 | C20H16N2OS (332) |
3a | -C4H3O | H | OAc | 194–196 | Ethanol/H2O | 76 | C34H34N2O10S (662) |
3b | 4-NO2-C6H5 | H | OAc | 172–174 | Ethanol/H2O | 75 | C36H35N3O11S (717) |
3c | 3-EtO,4-OH-C6H4 | H | OAc | 118–120 | Ethanol/H2O | 68 | C38H40N2O11S (732) |
3d | -C4H3O | OAc | H | 215–217 | Ethanol/H2O | 75 | C34H34N2O10S (662) |
3e | 4-NO2-C6H5 | OAc | H | 140–142 | Ethanol/H2O | 76 | C36H35N3O11S (717) |
3f | 3-EtO-4-OH-C6H4 | OAc | H | 175–177 | Ethanol/H2O | 79 | C38H40N2O11S (732) |
5a | 2,6-Cl2-C6H4 | H | OAc | 192–194 | Ethanol/H2O | 65 | C36H35Cl2N3O9 (724) |
5b | 2,6-Cl2-C6H4 | OAc | H | 205–207 | Ethanol/H2O | 70 | C36H35Cl2N3O9 (724) |
5c | 2,6-F2-C6H4 | H | OAc | 107–109 | Ethanol/H2O | 66 | C36H35F2N3O9 (691) |
5d | 2,6-F2-C6H4 | OAc | H | 132–134 | Ethanol/H2O | 72 | C36H35F2N3O9 (691) |
7a | 2,6-Cl2-C6H4 | --- | --- | 180–182 | Ethanol/H2O | 95 | C22H18Cl2N2O2 (413) |
7b | 2,6-F2-C6H4 | --- | --- | 170–172 | Ethanol/H2O | 92 | C22H18F2N2O2 (380) |
8a | 2,6-Cl2-C6H4 | OAc | H | 230–232 | Ethanol/H2O | 86 | C36H36Cl2N2O11 (743) |
8b | 2,6-F2-C6H4 | OAc | H | 155–157 | Ethanol/H2O | 85 | C36H36F2N2O11 (710) |
2.2. Molecular Modeling Study
Docking Using Autodock Vina
2.3. In Vitro Cytotoxic Screening
Compound | Anticancer effect % inhibition of cell viability | Affinity Kcal/mol | RMSD Deviation from best mode | |
---|---|---|---|---|
100 µg/mL | 50 µg/mL | |||
2b | 0 | 0 | −9.5 | 7.07 |
3a | 0 | 0 | −8.3 | 9.5 |
3b | 0 | 0 | −7.7 | 11.6 |
3c | 70% | 50% | −10.7 | 4.02 |
3d | 0 | 0 | −6.6 | 10.3 |
3e | 0 | 0 | −7.4 | 9.2 |
3f | 10% | 0 | −11.4 | 9.0 |
5b | 0 | 0 | −11.0 | 9.3 |
5c | 40% | 7% | −11.2 | 9.5 |
7a | 0 | 0 | −10.3 | 7.2 |
7b | 20% | 15% | −11.6 | 4.6 |
3. Experimental
3.1. Chemistry
3.1.1. General
3.1.2. Synthesis of 4-Aryl-6-(1,2,3,4-tetrahydronaphthalen-6-yl)-2-thioxo-1,2-dihydropyridine-3-carbonitriles 2a–c
3.1.3. Synthesis of 4-Aryl-6-(1,2,3,4-tetrahydronaphthalen-6-yl)-2-(2',3',4',6'-tetra-O-acetyl-β-D-gluco and galactopyranosyl thio)pyridine-3-carbonitriles 3a–f
3.1.4. Synthesis of 4-Aryl-6-(1,2,3,4-tetrahydronaphthalen-6-yl)-2-(2',3',4',6'-tetra-O-acetyl-β-D-gluco and galactopyranosyl imino)pyridine-3-carbonitriles 5a–d
3.1.5. Synthesis of 4-Aryl-6-(1,2,3,4-tetrahydronaphthalen-6-yl)-2-oxo-1,2-dihydropyridine-3-carboxamides 7a,b
3.1.6. Synthesis of 4-Aryl-N-(2',3',4',6'-tetra-O-acetyl-β-D-galactopyranosyl)-6-(1,2,3,4-tetrahydro-naphthalen-6-yl)-2-oxo-1,2-dihydro pyridine-3-carboxamides 8a,b
3.2. Molecular Modelling
3.3. In Vitro Cytotoxic Screening
3.3.1. Tumor
3.3.2. Animals
3.3.3. In Vitro Test for Cytotoxic Effect
4. Conclusions
Acknowledgments
References and Notes
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Al-Mutairi, M.S.; Al-Abdullah, E.S.; Haiba, M.E.; Khedr, M.A.; Zaghary, W.A. Synthesis, Molecular Docking and Preliminary in-Vitro Cytotoxic Evaluation of Some Substituted Tetrahydro-naphthalene (2',3',4',6'-Tetra-O-Acetyl-β-D-Gluco/-Galactopyranosyl) Derivatives. Molecules 2012, 17, 4717-4732. https://doi.org/10.3390/molecules17044717
Al-Mutairi MS, Al-Abdullah ES, Haiba ME, Khedr MA, Zaghary WA. Synthesis, Molecular Docking and Preliminary in-Vitro Cytotoxic Evaluation of Some Substituted Tetrahydro-naphthalene (2',3',4',6'-Tetra-O-Acetyl-β-D-Gluco/-Galactopyranosyl) Derivatives. Molecules. 2012; 17(4):4717-4732. https://doi.org/10.3390/molecules17044717
Chicago/Turabian StyleAl-Mutairi, Maha S., Ebtehal S. Al-Abdullah, Mogedda E. Haiba, Mohammed A. Khedr, and Wafaa A. Zaghary. 2012. "Synthesis, Molecular Docking and Preliminary in-Vitro Cytotoxic Evaluation of Some Substituted Tetrahydro-naphthalene (2',3',4',6'-Tetra-O-Acetyl-β-D-Gluco/-Galactopyranosyl) Derivatives" Molecules 17, no. 4: 4717-4732. https://doi.org/10.3390/molecules17044717