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Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-likeness, and Bioavailability

Year 2024, Volume: 45 Issue: 2, 282 - 290, 30.06.2024

Nihat Karakuş

https://doi.org/10.17776/csj.1403956

Abstract

Naturally-existing chemicals especially phytochemicals have been commonly used for medicinal purposes in terms of both traditional and contemporary respects. Allyl isothiocyanate structure exhibits antimicrobial and anticancer activity, whereas the allitridin, as one of the main components of the garlic, showed antifungal, antitumor, and antioxidant activity. Arabinose and galactose as monosaccharides also play a main role in drug-design research to facilitate drug delivery to target cells and regulate insulin resistance, respectively. Herein, the 3-isothiocyanatoprop-1-ene (Allyl isothiocyanate, AITC), 2,3,4,5-tetrahydroxypentanal (Ar, Arabinose), 1,3-diallyltrisulfane (Allitridin, DATS), 6-(hydroxymethyl)tetrahydro-2H-pyran-2,3,4,5-tetraol (Galactose, Gal), 6-methyltetrahydro-2H-pyran-2,3,4,5-tetraol (Rhamnose, Rh), and tetrahydro-2H-pyran-2,3,4,5-tetraol (cyclic-Arabinose, C-Ar) agents were investigated by using DFT. The B3LYP/6-311G** level computations were used to optimize the compounds' geometries and then to predict the reactivity indexes of the compounds. Also, lipophilicity and water-solubility features were determined to enlighten the physicochemical characteristics of the compounds. Then, the studied agents' pharmacokinetics were evaluated using the BOILED-Egg and radar graphs. Last, the bioavailability and drug-likeness behaviors were predicted. This trial work will be hoped to provide fundamental electronic and physicochemical insight into the relationship between drug-likeness and electronic structure.

Keywords

Phytochemicals Arabinose DFT study Lipophilicity& water solubility Drug-likeness

References

  • [1] Whittaker M. M., Whittaker J. W., The active site of galactose oxidase, Journal of Biological Chemistry, 263 (13) (1988) 6074-6080.
  • [2] Jansen L. M., van Rijbroe, K. W. M., den Bakker P. C., Klaassen-Heshof D. J., Kolkman W. J. B., Venbrux N., Migchielsen V., Hutzezon J., Lenferink W. B., Lücker S., Ranoux A., Raaijmakers H. W. C., Boltje T. J., Synthesis and Performance of Biobased Surfactants Prepared by the One-Pot Reductive Amination of l-Arabinose and d-Galacturonic Acid, ACS Sustainable Chemistry & Engineering, 11 (45) (2023) 16117-16123.
  • [3] Seki T., Hosono T., Hosono-Fukao T., Inada K., Tanaka R., Ogihara J., Ariga T., Anticancer effects of diallyl trisulfide derived from garlic, Asia Pac. J. Clin. Nutr., 17 (1) (2008) 249-252.
  • [4] Puccinelli M. T., Stan S. D., Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment, International Journal of Molecular Sciences, 18(8) (2017) 1645.
  • [5] Powolny A. A., Singh S. V., Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds, Cancer Letters, 269(2) (2008) 305-314.
  • [6] Lai K. C., Hs S. C., Kuo, C. L., Yang J. S., Ma C. Y., Lu H. F., Tang N., Hsia T., Ho H., Chung J. G., Diallyl sulfide, diallyl disulfide, and diallyl trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase‐2,‐7, and‐9 expressions, Environmental Toxicology, 28(9) (2013) 479-488.
  • [7] Blažević I., Đulović A., Maravić A., Čikeš Čulić V., Montaut S., Rollin P., Antimicrobial and cytotoxic activities of Lepidium latifolium L. Hydrodistillate, extract and its major sulfur volatile allyl isothiocyanate, Chemistry & Biodiversity, 16(4) (2019) e1800661.
  • [8] Kelly C. L., Taylor G. M., Hitchcock A., Torres-Méndez, A., Heap, J. T., A Rhamnose-Inducible System for Precise and Temporal Control of Gene Expression in Cyanobacteria, ACS Synthetic Biology, 7(4) (2018) 1056-1066.
  • [9] Kelly C. L., Liu Z., Yoshihara A., Jenkinson S. F., Wormald M. R., Otero J., Estévez A., Kato A., Marqvorsen M. H. S., Fleet G. W. J., Estévez R. J., Izumori K., Heap J. T., Synthetic Chemical Inducers and Genetic Decoupling Enable Orthogonal Control of the rhaBAD Promoter, ACS Synthetic Biology, 5(10) (2016) 1136-1145.
  • [10] Tomsik P., Soukup T., Cermakova E., Micuda S., Niang M., Sucha L., Rezacova M., L-rhamnose and L-fucose suppress cancer growth in mice, Central European Journal of Biology, 6 (2011) 1-9.
  • [11] Lin H., Ramesh S., Chang Y., Tsai C., Tsai C., Shibu M. A., Tamilselvi S., Mahalakshmi B., Kuo W., Huang C., D‐galactose‐induced toxicity associated senescence mitigated by alpinate oxyphyllae fructus fortified adipose‐derived mesenchymal stem cells, Environmental Toxicology, 36(1) (2021) 86-94.
  • [12] Liu G., Hale G. E., Hughes C. L., Galactose metabolism and ovarian toxicity, Reproductive Toxicology, 14(5) (2000) 377-384.
  • [13] Coba‐Jiménez L., Maza J., Guerra M., Deluque‐Gómez J., Cubillán N., Interaction of Ciprofloxacin with Arabinose, Glucosamine, Glucuronic Acid and Rhamnose: Insights from Genetic Algorithm and Quantum Chemistry, Chemistry Select, 7(2) (2022) e202103836.
  • [14] Su Y., Chen L., Cheng Y., Zhang F., Su Y., Li Z., Raman spectroscopic characteristics of diallyl trisulfide acting on trans‐crotonaldehyde, Journal of Raman Spectroscopy, 46(11) (2015) 1067-1072.
  • [15] Dehghani A., Mostafatabar A. H., Ramezanzadeh B., Synergistic anticorrosion effect of Brassica Hirta phytoconstituents and cerium ions on mild steel in saline media: Surface and electrochemical evaluations, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 656 (2023) 130503.
  • [16] Frisch M. J., Gaussian 09W, Revision D.01, Gaussian, Inc, Wallingford CT, (2013).
  • [17] Becke A. D., A new mixing of Hartree–Fock and local density‐functional theories, J. Chem. Phys., 98 (1993) 1372-1377.
  • [18] Lee C., Yang W., Parr R. G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Phys. Rev., B37 (1988) 785-789.
  • [19] Raghavachari K., Binkley J. S., Seeger R., Pople J. A., Self-Consistent Molecular Orbital Methods. 20. Basis set for correlated wave-functions, J. Chem. Phys., 72 (1980) 650-654.
  • [20] GaussView 6.0.16, Gaussian, Inc, Wallingford CT, 2016.
  • [21] Herzberg G., Molecular Spectra and Molecular Structure III, 1st Edition, D. Van Nostrand Company, Inc., New York, (1964).
  • [22] Serdaroglu G., Durmaz S., DFT and statistical mechanics entropy calculations of diatomic and polyatomic molecules, Indian J. Chem., 49 (2010) 861-866.
  • [23] Koopmans T., Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms, Physica, 1 (1934) 104-113.
  • [24] Perdew J. P., Parr R. G., Levy M., Balduz J. L., Density-Functional Theory for Fractional Particle Number: Derivative Discontinuities of the Energy, Phys. Rev. Lett., 49(23) (1982) 1691-1694.
  • [25] Parr R. G., Pearson R. G., Absolute hardness: companion parameter to absolute electronegativity, J. Am. Chem. Soc., 105 (1983) 7512-7516.
  • [26] Gazquez J. L., Cedillo A., Vela A., Electrodonating and Electroaccepting Powers, J. Phys. Chem. A, 111 (10) (2007) 1966-1970.
  • [27] Gomez B., Likhanova N. V., Domínguez-Aguilar M. A., Martínez-Palou R., Vela A., Gazquez J. L., Quantum Chemical Study of the Inhibitive Properties of 2-Pyridyl-Azoles, J. Phys. Chem. B, 110(18) (2006) 8928-8934.
  • [28] Daina A., Michielin O., Zoete V., iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach, J. Chem. Inf. Model., 54(12) (2014) 3284-3301.
  • [29] Cheng T., Zhao Y., Li X., Lin F., X Y., Zhang, X., Lai L., Computation of octanol−water partition coefficients by guiding an additive model with knowledge, J. Chem. Inf. Model., 47(6) (2007) 2140-2148.
  • [30] Wildman S. A., Crippen G. M., Prediction of physicochemical parameters by atomic contributions, J. Chem. Inf. Comp. Sci., 39(5) (1999) 868-873.
  • [31] Lipinski C. A., Lombardo F., Dominy B. W., Feeney P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev., 64 (2012) 4-17.
  • [32] Computational approaches streamlining drug discovery. Available at: https://www.silicos-it.be. Retrieved April 28, (2023).
  • [33] Daina A., Michielin O., Zoete V., SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of small molecules, Sci. Rep.-UK, 7(1) (2017) 1-13.
  • [34] Ali J., Camilleri P., Brown M. B., Hutt A. J., Kirton S. B., In silico prediction of aqueous solubility using simple QSPR models: the importance of phenol and phenol-like moieties, J. Chem. Inf. Model., 52(11) (2012) 2950-2957.
  • [35] Delaney J. S., ESOL: estimating aqueous solubility directly from molecular structure, J. Chem. Inf. Comp. Sci., 44(3) (2004) 1000-1005.
  • [36] Ghose A. K., Viswanadhan V. N., Wendoloski J. J., A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases, J. Comb. Chem., 1(1) (1999) 55-68.
  • [37] Veber D. F., Johnson S. R., Cheng H. Y., Smith B. R., Ward K. W., Kopple K. D., Molecular properties that influence the oral bioavailability of drug candidates, J. Med. Chem., 45(12) (2002) 2615-2623.
  • [38] Egan W. J., Merz K. M., Baldwin J. J., Prediction of drug absorption using multivariate statistics, J. Med. Chem., 43(21) (2000) 3867-3877.
  • [39] Muegge I., Heald S. L., Brittelli D., Simple selection criteria for drug-like chemical matter, J. Med. Chem., 44(12) (2001) 1841-1846.
  • [40] Martin Y. C., A bioavailability score, J. Med. Chem., 48(9) (2005) 3164-3170.

Year 2024, Volume: 45 Issue: 2, 282 - 290, 30.06.2024

Nihat Karakuş

https://doi.org/10.17776/csj.1403956

Abstract

References

  • [1] Whittaker M. M., Whittaker J. W., The active site of galactose oxidase, Journal of Biological Chemistry, 263 (13) (1988) 6074-6080.
  • [2] Jansen L. M., van Rijbroe, K. W. M., den Bakker P. C., Klaassen-Heshof D. J., Kolkman W. J. B., Venbrux N., Migchielsen V., Hutzezon J., Lenferink W. B., Lücker S., Ranoux A., Raaijmakers H. W. C., Boltje T. J., Synthesis and Performance of Biobased Surfactants Prepared by the One-Pot Reductive Amination of l-Arabinose and d-Galacturonic Acid, ACS Sustainable Chemistry & Engineering, 11 (45) (2023) 16117-16123.
  • [3] Seki T., Hosono T., Hosono-Fukao T., Inada K., Tanaka R., Ogihara J., Ariga T., Anticancer effects of diallyl trisulfide derived from garlic, Asia Pac. J. Clin. Nutr., 17 (1) (2008) 249-252.
  • [4] Puccinelli M. T., Stan S. D., Dietary Bioactive Diallyl Trisulfide in Cancer Prevention and Treatment, International Journal of Molecular Sciences, 18(8) (2017) 1645.
  • [5] Powolny A. A., Singh S. V., Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds, Cancer Letters, 269(2) (2008) 305-314.
  • [6] Lai K. C., Hs S. C., Kuo, C. L., Yang J. S., Ma C. Y., Lu H. F., Tang N., Hsia T., Ho H., Chung J. G., Diallyl sulfide, diallyl disulfide, and diallyl trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase‐2,‐7, and‐9 expressions, Environmental Toxicology, 28(9) (2013) 479-488.
  • [7] Blažević I., Đulović A., Maravić A., Čikeš Čulić V., Montaut S., Rollin P., Antimicrobial and cytotoxic activities of Lepidium latifolium L. Hydrodistillate, extract and its major sulfur volatile allyl isothiocyanate, Chemistry & Biodiversity, 16(4) (2019) e1800661.
  • [8] Kelly C. L., Taylor G. M., Hitchcock A., Torres-Méndez, A., Heap, J. T., A Rhamnose-Inducible System for Precise and Temporal Control of Gene Expression in Cyanobacteria, ACS Synthetic Biology, 7(4) (2018) 1056-1066.
  • [9] Kelly C. L., Liu Z., Yoshihara A., Jenkinson S. F., Wormald M. R., Otero J., Estévez A., Kato A., Marqvorsen M. H. S., Fleet G. W. J., Estévez R. J., Izumori K., Heap J. T., Synthetic Chemical Inducers and Genetic Decoupling Enable Orthogonal Control of the rhaBAD Promoter, ACS Synthetic Biology, 5(10) (2016) 1136-1145.
  • [10] Tomsik P., Soukup T., Cermakova E., Micuda S., Niang M., Sucha L., Rezacova M., L-rhamnose and L-fucose suppress cancer growth in mice, Central European Journal of Biology, 6 (2011) 1-9.
  • [11] Lin H., Ramesh S., Chang Y., Tsai C., Tsai C., Shibu M. A., Tamilselvi S., Mahalakshmi B., Kuo W., Huang C., D‐galactose‐induced toxicity associated senescence mitigated by alpinate oxyphyllae fructus fortified adipose‐derived mesenchymal stem cells, Environmental Toxicology, 36(1) (2021) 86-94.
  • [12] Liu G., Hale G. E., Hughes C. L., Galactose metabolism and ovarian toxicity, Reproductive Toxicology, 14(5) (2000) 377-384.
  • [13] Coba‐Jiménez L., Maza J., Guerra M., Deluque‐Gómez J., Cubillán N., Interaction of Ciprofloxacin with Arabinose, Glucosamine, Glucuronic Acid and Rhamnose: Insights from Genetic Algorithm and Quantum Chemistry, Chemistry Select, 7(2) (2022) e202103836.
  • [14] Su Y., Chen L., Cheng Y., Zhang F., Su Y., Li Z., Raman spectroscopic characteristics of diallyl trisulfide acting on trans‐crotonaldehyde, Journal of Raman Spectroscopy, 46(11) (2015) 1067-1072.
  • [15] Dehghani A., Mostafatabar A. H., Ramezanzadeh B., Synergistic anticorrosion effect of Brassica Hirta phytoconstituents and cerium ions on mild steel in saline media: Surface and electrochemical evaluations, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 656 (2023) 130503.
  • [16] Frisch M. J., Gaussian 09W, Revision D.01, Gaussian, Inc, Wallingford CT, (2013).
  • [17] Becke A. D., A new mixing of Hartree–Fock and local density‐functional theories, J. Chem. Phys., 98 (1993) 1372-1377.
  • [18] Lee C., Yang W., Parr R. G., Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Phys. Rev., B37 (1988) 785-789.
  • [19] Raghavachari K., Binkley J. S., Seeger R., Pople J. A., Self-Consistent Molecular Orbital Methods. 20. Basis set for correlated wave-functions, J. Chem. Phys., 72 (1980) 650-654.
  • [20] GaussView 6.0.16, Gaussian, Inc, Wallingford CT, 2016.
  • [21] Herzberg G., Molecular Spectra and Molecular Structure III, 1st Edition, D. Van Nostrand Company, Inc., New York, (1964).
  • [22] Serdaroglu G., Durmaz S., DFT and statistical mechanics entropy calculations of diatomic and polyatomic molecules, Indian J. Chem., 49 (2010) 861-866.
  • [23] Koopmans T., Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms, Physica, 1 (1934) 104-113.
  • [24] Perdew J. P., Parr R. G., Levy M., Balduz J. L., Density-Functional Theory for Fractional Particle Number: Derivative Discontinuities of the Energy, Phys. Rev. Lett., 49(23) (1982) 1691-1694.
  • [25] Parr R. G., Pearson R. G., Absolute hardness: companion parameter to absolute electronegativity, J. Am. Chem. Soc., 105 (1983) 7512-7516.
  • [26] Gazquez J. L., Cedillo A., Vela A., Electrodonating and Electroaccepting Powers, J. Phys. Chem. A, 111 (10) (2007) 1966-1970.
  • [27] Gomez B., Likhanova N. V., Domínguez-Aguilar M. A., Martínez-Palou R., Vela A., Gazquez J. L., Quantum Chemical Study of the Inhibitive Properties of 2-Pyridyl-Azoles, J. Phys. Chem. B, 110(18) (2006) 8928-8934.
  • [28] Daina A., Michielin O., Zoete V., iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach, J. Chem. Inf. Model., 54(12) (2014) 3284-3301.
  • [29] Cheng T., Zhao Y., Li X., Lin F., X Y., Zhang, X., Lai L., Computation of octanol−water partition coefficients by guiding an additive model with knowledge, J. Chem. Inf. Model., 47(6) (2007) 2140-2148.
  • [30] Wildman S. A., Crippen G. M., Prediction of physicochemical parameters by atomic contributions, J. Chem. Inf. Comp. Sci., 39(5) (1999) 868-873.
  • [31] Lipinski C. A., Lombardo F., Dominy B. W., Feeney P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev., 64 (2012) 4-17.
  • [32] Computational approaches streamlining drug discovery. Available at: https://www.silicos-it.be. Retrieved April 28, (2023).
  • [33] Daina A., Michielin O., Zoete V., SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness, and medicinal chemistry friendliness of small molecules, Sci. Rep.-UK, 7(1) (2017) 1-13.
  • [34] Ali J., Camilleri P., Brown M. B., Hutt A. J., Kirton S. B., In silico prediction of aqueous solubility using simple QSPR models: the importance of phenol and phenol-like moieties, J. Chem. Inf. Model., 52(11) (2012) 2950-2957.
  • [35] Delaney J. S., ESOL: estimating aqueous solubility directly from molecular structure, J. Chem. Inf. Comp. Sci., 44(3) (2004) 1000-1005.
  • [36] Ghose A. K., Viswanadhan V. N., Wendoloski J. J., A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases, J. Comb. Chem., 1(1) (1999) 55-68.
  • [37] Veber D. F., Johnson S. R., Cheng H. Y., Smith B. R., Ward K. W., Kopple K. D., Molecular properties that influence the oral bioavailability of drug candidates, J. Med. Chem., 45(12) (2002) 2615-2623.
  • [38] Egan W. J., Merz K. M., Baldwin J. J., Prediction of drug absorption using multivariate statistics, J. Med. Chem., 43(21) (2000) 3867-3877.
  • [39] Muegge I., Heald S. L., Brittelli D., Simple selection criteria for drug-like chemical matter, J. Med. Chem., 44(12) (2001) 1841-1846.
  • [40] Martin Y. C., A bioavailability score, J. Med. Chem., 48(9) (2005) 3164-3170.
There are 40 citations in total.

Details

Primary Language English
Subjects Physical Organic Chemistry
Journal Section Natural Sciences
Authors

Nihat Karakuş 0000-0001-6223-7669

Publication Date June 30, 2024
Submission Date December 12, 2023
Acceptance Date March 30, 2024
Published in Issue Year 2024Volume: 45 Issue: 2

Cite

APA Karakuş, N. (2024). Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-likeness, and Bioavailability. Cumhuriyet Science Journal, 45(2), 282-290. https://doi.org/10.17776/csj.1403956
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