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

Nihat Karakuş

doi:10.17776/csj.1403956

EN

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

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.

Details

Primary Language

English

Subjects

Physical Organic Chemistry

Journal Section

Research Article

Authors

Nihat Karakuş ^*
0000-0001-6223-7669
Türkiye

Publication Date

June 30, 2024

Submission Date

December 12, 2023

Acceptance Date

March 30, 2024

Published in Issue

Year 2024 Volume: 45 Number: 2

DOI

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

IZ

https://izlik.org/JA58WN49XX

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

AMA

1.Karakuş N. Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-likeness, and Bioavailability. CSJ. 2024;45(2):282-290. doi:10.17776/csj.1403956

Chicago

Karakuş, Nihat. 2024. “Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-Likeness, and Bioavailability”. Cumhuriyet Science Journal 45 (2): 282-90. https://doi.org/10.17776/csj.1403956.

EndNote

Karakuş N (June 1, 2024) Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-likeness, and Bioavailability. Cumhuriyet Science Journal 45 2 282–290.

IEEE

[1]N. Karakuş, “Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-likeness, and Bioavailability”, CSJ, vol. 45, no. 2, pp. 282–290, June 2024, doi: 10.17776/csj.1403956.

ISNAD

Karakuş, Nihat. “Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-Likeness, and Bioavailability”. Cumhuriyet Science Journal 45/2 (June 1, 2024): 282-290. https://doi.org/10.17776/csj.1403956.

JAMA

1.Karakuş N. Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-likeness, and Bioavailability. CSJ. 2024;45:282–290.

MLA

Karakuş, Nihat. “Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-Likeness, and Bioavailability”. Cumhuriyet Science Journal, vol. 45, no. 2, June 2024, pp. 282-90, doi:10.17776/csj.1403956.

Vancouver

1.Nihat Karakuş. Theoretical Investigations on Phytochemicals: Physical Chemistry, FMO, MEP, Lipophilicity, Water Solubility, Drug-likeness, and Bioavailability. CSJ. 2024 Jun. 1;45(2):282-90. doi:10.17776/csj.1403956

Cited By

Synthesis, Characterization, Molecular Docking, and DFT Studies of 2,3,5-Trisubstituted-1,3,4-Oxadiazol-3(2H)-yl Methanone Derivatives

Journal of Computational Biophysics and Chemistry

https://doi.org/10.1142/S2737416525500528

Chalcone–sulfonate ester derivatives as dual urease and α-amylase inhibitors: synthesis, biological evaluation and integrated computational studies

RSC Advances

https://doi.org/10.1039/D6RA02588A

Identification of Potential Therapeutic Phytochemicals and Candidate Biomarkers for Osteomyelitis Using Network Pharmacology and Molecular Docking Approaches

Computational Biology and Chemistry

https://doi.org/10.1016/j.compbiolchem.2026.109140

As of 2026, Cumhuriyet Science Journal will be published in six issues per year, released in February, April, June, August, October, and December