Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor

Sevtap Çağlar Yavuz

doi:10.31466/kfbd.1307190

EN TR

Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor

Abstract

Natural products have historically made a significant contribution to pharmacotherapy, especially for cancer diseases. Garlic contains a variety of bioactive molecules with anticancer effects, including allicin and diallyl disulfide. In this study, optimization computations were performed in the Gaussian 09 W utilizing the DFT with functional B3LYP method/6-31++G(d,p) basis set for allicin and diallyl disulfide. Drug-likeness and ADME-Tox properties were examined. Molecular docking was achieved to research the biological knowledge of allicin and diallyl disulfide. The protein preferred in these computations is the crystal structure of the 5XGN, EGFR mutants T790M/C797S complex. The binding energies for the allicin and diallyl disulfide molecules-EGFR mutants T790M/C797S complex were computed as -8.3 kcal/mol and -8.2 kcal/mol respectively. Meaningful results were achieved for these two compounds.

Keywords

Allicin, Diallyl disulfide, DFT, HOMO-LUMO, Molecular docking, Garlic

Allisin ve Diallil Disülfitin Moleküler Yerleştirme ve Reaktif Bölgelerinin Tanımlanması (Homo–Lumo, Mep): Potansiyel Antikanser İnhibitörü

Abstract

Doğal ürünler tarihsel olarak, özellikle kanser hastalıkları için farmakoterapiye önemli bir katkı sağlamıştır. Sarımsak, allisin ve diallil disülfit dahil olmak üzere antikanser etkileri olan çeşitli biyoaktif moleküller içerir. Bu çalışmada, allisin ve diallil disülfit için fonksiyonel B3LYP yöntemi/6-31++G(d,p) temel seti ile DFT kullanılarak Gaussian 09 W'da optimizasyon hesaplamaları yapılmıştır. İlaca benzerlik ve absorpsiyon, dağılım, metabolizma, atılım ve toksisite (ADMET) özellikleri incelendi. Allisin ve diallil disülfitin biyolojik bilgisini araştırmak için moleküler yerleştirme gerçekleştirildi. Bu hesaplamalarda tercih edilen protein, 5XGN, EGFR mutantları T790M/C797S kompleksinin kristal yapısıdır. Allisin ve diallil disülfit molekülleri-EGFR mutantları T790M/C797S kompleksi için bağlanma enerjileri sırasıyla -8.3 kcal/mol ve -8.2 kcal/mol olarak hesaplandı. Bu iki bileşik için anlamlı sonuçlar elde edildi.

Keywords

Allisin, Diallil disülfit, DFT, HOMO-LUMO, Moleküler yerleştirme, Sarımsak

References

Akan, S. (2014). Health Promoting Properties of Garlic (Allium sativum L.) Consumption. Akademik Gıda, 12(2), 95-100.
Ali Abdalla, Y. O., Subramaniam, B., Nyamathulla, S., Shamsuddin, N., Arshad, N. M., Mun, K. S., Awang, K., Nagoor, N. H. (2022). Natural products for cancer therapy: a review of their mechanism of actions and toxicity in the past decade. Journal of Tropical Medicine, 2022.
Bailly, C. (2019). Irinotecan: 25 years of cancer treatment. Pharmacological research, 148, 104398.
Baldwin, E. L., and Osheroff, N. (2005). Etoposide, topoisomerase II and cancer. Current Medicinal Chemistry-Anti-Cancer Agents, 5(4), 363-372.
Banerjee, P., and Ulker, O. C. (2022). Combinative ex vivo studies and in silico models ProTox-II for investigating the toxicity of chemicals used mainly in cosmetic products. Toxicology mechanisms and methods, 32(7), 542-548.
Bayoumy, A. M., Ibrahim, M., Omar, A. (2020). Mapping molecular electrostatic potential (MESP) for fulleropyrrolidine and its derivatives. Optical and Quantum Electronics, 52, 1-13.
Bazaraliyeva, A., Moldashov, D., Turgumbayeva, A., Kartbayeva, E., Kalykova, A., Sarsenova, L., & Issayeva, R. (2022). Chemical and biological properties of bio-active compounds from garlic (Allium sativum). Pharmacia, 69(4), 955-964.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 68(6), 394-424.
Bulat, F. A., Toro-Labbé, A., Brinck, T., Murray, J. S., Politzer, P. (2010). Quantitative analysis of molecular surfaces: areas, volumes, electrostatic potentials and average local ionization energies. Journal of molecular modeling, 16, 1679-1691.
Butt, S. S., Badshah, Y., Shabbir, M., Rafiq, M. (2020). Molecular docking using chimera and autodock vina software for nonbioinformaticians. JMIR Bioinformatics and Biotechnology, 1(1), e14232.

Chakraborty, S., Rahman, T. (2012). The difficulties in cancer treatment. Ecancermedicalscience, 6.
Choudhari, A. S., Mandave, P. C., Deshpande, M., Ranjekar, P., Prakash, O. (2020). Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Frontiers in pharmacology, 10, 1614.
D.S.J.S.D. Biovia, CA, USA, Discovery Studio Visualizer, 2017, 936.
Daina, A., Michielin, O., Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports, 7(1), 42717.
Dehelean, C. A., Marcovici, I., Soica, C., Mioc, M., Coricovac, D., Iurciuc, S., Cretu O. M., Pinzaru, I. (2021). Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules, 26(4), 1109.
Desale, V. J., Mali, S. N., Thorat, B. R., Yamgar, R. S. (2021). Synthesis, admetSAR predictions, DPPH radical scavenging activity, and potent anti-mycobacterial studies of hydrazones of substituted 4-(anilino methyl) benzohydrazides (Part 2). Current Computer-Aided Drug Design, 17(4), 493-503.
Di, L., Kerns, E. H., Carter, G. T. (2009). Drug-like property concepts in pharmaceutical design. Current pharmaceutical design, 15(19), 2184-2194.
Diretto, G., Rubio-Moraga, A., Argandoña, J., Castillo, P., Gómez-Gómez, L., Ahrazem, O. (2017). Tissue-specific accumulation of sulfur compounds and saponins in different parts of garlic cloves from purple and white ecotypes. Molecules, 22(8), 1359.
El-Saber Batiha, G., Magdy Beshbishy, A., G. Wasef, L., Elewa, Y. H., A. Al-Sagan, A., Abd El-Hack, M. E., Taha, A. E., Abd-Elhakim, Y. M., Prasad Devkota, H. (2020). Chemical constituents and pharmacological activities of garlic (Allium sativum L.): A review. Nutrients, 12(3), 872.
Gaussian 09, Revision A. 1; Gaussian, Inc: Wallingford, CT, 2009
Gfeller, D., Grosdidier, A., Wirth, M., Daina, A., Michielin, O., Zoete, V. (2014). SwissTargetPrediction: a web server for target prediction of bioactive small molecules. Nucleic acids research, 42(W1), W32-W38.
Giaccone, G., Donadio, M., Bonardi, G., Testore, F., Calciati, A. (1988). Teniposide in the treatment of small-cell lung cancer: the influence of prior chemotherapy. Journal of Clinical Oncology, 6(8), 1264-1270.
Goktas, F., Karatas, M., Tuncer, S. C., Karacaer, N. T. (2023). Investigation of the Effect of Natural Bioactive Components on iNOS Activity in-Slico. Aksaray Üniversitesi Tıp Bilimleri Dergisi, 4(1), 12-17.
Guéniche, N., Huguet, A., Bruyere, A., Habauzit, D., Le Hégarat, L., Fardel, O. (2021). Comparative in silico prediction of P‐glycoprotein‐mediated transport for 2010–2020 US FDA‐approved drugs using six Web‐tools. Biopharmaceutics & Drug Disposition, 42(8), 393-398.
Gundogdu, Ö. (2023). Molecular docking studies and ADME predictions on synthesized chalcone compounds targeting EGFR. Hittite Journal of Science and Engineering, 10(2), 167-175.
Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., Sarkar, S. (2014). Drug resistance in cancer: an overview. Cancers, 6(3), 1769-1792.
Huizing, M. T., Misser, V. H. S., Pieters, R. C., ten Bokkel Huinink, W. W., Veenhof, C. H. N., Vermorken, J. B., Pinedo, H. M., Beijnen, J. H. (1995). Taxanes: a new class of antitumor agents. Cancer investigation, 13(4), 381-404
Iqbal, J., Abbasi, B. A., Mahmood, T., Kanwal, S., Ali, B., Shah, S. A., Khalil, A. T. (2017). Plant-derived anticancer agents: A green anticancer approach. Asian Pacific Journal of Tropical Biomedicine, 7(12), 1129-1150.
Kasmi, R., El Ouardi, Y., Bouachrine, M., Ouammou, A. (2022). Modeling study, 3D-QSAR and molecular docking of 9H-purine derivatives as EGFR inhibitors. Materials Today: Proceedings, 62, 6312-6323.
Kerns, E. H., Di, L. (2003). Pharmaceutical profiling in drug discovery. Drug discovery today, 8(7), 316-323.
Kuete, V. (2017). Allium sativum. In Medicinal Spices and Vegetables from Africa, 363-377.
Liu, Y. P., Zheng, C. C., Huang, Y. N., He, M. L., Xu, W. W., Li, B. (2021). Molecular mechanisms of chemo‐and radiotherapy resistance and the potential implications for cancer treatment. MedComm, 2(3), 315-340.
Martino, E., Casamassima, G., Castiglione, S., Cellupica, E., Pantalone, S., Papagni, F., Rui, M., Siciliano, A. M., Collina, S. (2018). Vinca alkaloids and analogues as anti-cancer agents: Looking back, peering ahead. Bioorganic & medicinal chemistry letters, 28(17), 2816-2826.
Martins, N., Petropoulos, S., Ferreira, I. C. (2016). Chemical composition and bioactive compounds of garlic (Allium sativum L.) as affected by pre-and post-harvest conditions: A review. Food Chemistr, 211, 41-50.
Mary, Y. S., Varghese, H. T., Panicker, C. Y., Thiemann, T., Al-Saadi, A. A., Popoola, S. A., Alsenoy, C.V., Al Jasem, Y. (2015). Molecular conformational analysis, vibrational spectra, NBO, NLO, HOMO–LUMO and molecular docking studies of ethyl 3-(E)-(anthracen-9-yl) prop-2-enoate based on density functional theory calculations. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 150, 533-542.
Miller, K. D., Siegel, R. L., Lin, C. C., Mariotto, A. B., Kramer, J. L., Rowland, J. H., Stein, K. D., Alteri, R., Jemal, A. (2016). Cancer treatment and survivorship statistics, 2016. CA: a cancer journal for clinicians, 66(4), 271-289.
Mitra, S., Das, R., Emran, T. B., Labib, R. K., Tabassum, N. E., Islam, F., Sharma, R., Ahmad, I., Nainu, F., Chidambaram, K., Alhumaydhi, F. A., Chandran, D., Capasso, R., Wilairatana, P. (2022). Diallyl disulfide: A bioactive garlic compound with anticancer potential. Frontiers in Pharmacology, 13.
Mitsudomi, T., Yatabe, Y. (2010). Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. The FEBS journal, 277(2), 301-308.
Mohammed, H. A., Emwas, A. H., Khan, R. A. (2023). Salt-Tolerant Plants, Halophytes, as Renewable Natural Resources for Cancer Prevention and Treatment: Roles of Phenolics and Flavonoids in Immunomodulation and Suppression of Oxidative Stress towards Cancer Management. International Journal of Molecular Sciences, 24(6), 5171.
Pantaleão, S. Q., Fernandes, P. O., Gonçalves, J. E., Maltarollo, V. G., Honorio, K. M. (2022). Recent advances in the prediction of pharmacokinetics properties in drug design studies: a review. ChemMedChem, 17(1), e202100542.
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., Ferrin, T. E. (2004). UCSF Chimera—a visualization system for exploratory research and analysis. Journal of computational chemistry, 25(13), 1605-1612.
Pulte, D., and Brenner, H. (2010). Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. The oncologist, 15(9), 994-1001.
Rayan, A., Raiyn, J., Falah, M. (2017). Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity. PloS one, 12(11), e0187925.
Rekowska, E., and Skupień, K. (2009). The influence of selected agronomic practices on the yield and chemical composition of winter garlic. Journal of Fruit and Ornamental Plant Research, 70(1), 173-182.
Rouf, R., Uddin, S. J., Sarker, D. K., Islam, M. T., Ali, E. S., Shilpi, J. A., Nahar, L., Tiralongo, E., Sarker, S. D. (2020). Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data. Trends in food science & technology, 104, 219-234.
Shaker, B., Ahmad, S., Lee, J., Jung, C., Na, D. (2021). In silico methods and tools for drug discovery. Computers in biology and medicine, 137, 104851.
Spartan'10, version 1.1.0. Wavefunction, Inc. Irvine, CA. 2010.
Suresh, C. H., Remya, G. S., Anjalikrishna, P. K. (2022). Molecular electrostatic potential analysis: A powerful tool to interpret and predict chemical reactivity. Wiley Interdisciplinary Reviews: Computational Molecular Science, 12(5), e1601
Talib, W. H. (2017). Consumption of garlic and lemon aqueous extracts combination reduces tumor burden by angiogenesis inhibition, apoptosis induction, and immune system modulation. Nutrition, 43, 89-97.
Tavares, L., Santos, L., Noreña, C. P. Z. (2021). Bioactive compounds of garlic: A comprehensive review of encapsulation technologies, characterization of the encapsulated garlic compounds and their industrial applicability. Trends in Food Science & Technology, 114, 232-244
Wang, Y., Xiao, J., Suzek, T. O., Zhang, J., Wang, J., Bryant, S. H. (2009). PubChem: a public information system for analyzing bioactivities of small molecules. Nucleic acids research, 37(suppl_2), W623-W633.
Wangchuk, P. (2018). Therapeutic applications of natural products in herbal medicines, biodiscovery programs, and biomedicine. Journal of Biologically Active Products from Nature, 8(1), 1-20.
Yavuz, S. Ç. (2023). Molecular docking studies and structural&electronic analysis of gefarnate. Journal of the Indian Chemical Society, 100(4), 100971.
Zhang, Z., Lee, J. C., Lin, L., Olivas, V., Au, V., LaFramboise, T., Abdel-Rahman, M., Wang, X., Levine, A.D., Rho, J.K., Choi, Y.J., Choi, C. M., Kim, S. W., Jang, S. J., Park, Y. S., Kim, W. S., Lee, D. H., Lee, J. S., Miller, V. A., Arcila, M., Ladanyi, M., Moonsamy, P., Sawyers, C. Boggon, T. J., Ma, P. C., Costa, C., Taron, M., Rosell, R., Halmos, B., Bivona, T. G. (2012). Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nature Genetics, 44(8), 852-860.
Zhao, H., Wu, L., Yan, G., Chen, Y., Zhou, M., Wu, Y., Li, Y. (2021). Inflammation and tumor progression: signaling pathways and targeted intervention. Signal transduction and targeted therapy, 6(1), 263.

Details

Primary Language

English

Subjects

Chemical Engineering (Other)

Journal Section

Research Article

Authors

Sevtap Çağlar Yavuz ^*
0000-0001-6497-2907
Türkiye

Early Pub Date

December 18, 2023

Publication Date

December 15, 2023

Submission Date

May 30, 2023

Acceptance Date

October 23, 2023

Published in Issue

Year 2023 Volume: 13 Number: 4

DOI

https://doi.org/10.31466/kfbd.1307190

IZ

https://izlik.org/JA83KC44MU

APA

Çağlar Yavuz, S. (2023). Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor. Karadeniz Fen Bilimleri Dergisi, 13(4), 1523-1539. https://doi.org/10.31466/kfbd.1307190

AMA

1.Çağlar Yavuz S. Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor. KFBD. 2023;13(4):1523-1539. doi:10.31466/kfbd.1307190

Chicago

Çağlar Yavuz, Sevtap. 2023. “Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor”. Karadeniz Fen Bilimleri Dergisi 13 (4): 1523-39. https://doi.org/10.31466/kfbd.1307190.

EndNote

Çağlar Yavuz S (December 1, 2023) Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor. Karadeniz Fen Bilimleri Dergisi 13 4 1523–1539.

IEEE

[1]S. Çağlar Yavuz, “Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor”, KFBD, vol. 13, no. 4, pp. 1523–1539, Dec. 2023, doi: 10.31466/kfbd.1307190.

ISNAD

Çağlar Yavuz, Sevtap. “Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor”. Karadeniz Fen Bilimleri Dergisi 13/4 (December 1, 2023): 1523-1539. https://doi.org/10.31466/kfbd.1307190.

JAMA

1.Çağlar Yavuz S. Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor. KFBD. 2023;13:1523–1539.

MLA

Çağlar Yavuz, Sevtap. “Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor”. Karadeniz Fen Bilimleri Dergisi, vol. 13, no. 4, Dec. 2023, pp. 1523-39, doi:10.31466/kfbd.1307190.

Vancouver

1.Sevtap Çağlar Yavuz. Molecular Docking and Reactive Sites Identification (Homo–Lumo, Mep) of Allicin and Diallyl Disulfide: Potential Anticancer Inhibitor. KFBD. 2023 Dec. 1;13(4):1523-39. doi:10.31466/kfbd.1307190

Cited By

Synthesis of new two 1,2-disubstituted benzimidazole compounds: their in vitro anticancer and in silico molecular docking studies

BMC Chemistry

https://doi.org/10.1186/s13065-024-01241-z

Synthesis, Characterization, Biological Evaluation, DFT Calculations, and Molecular Docking Study of Transition Metal Complexes Derived From a Schiff Base Ligand

Chemistry & Biodiversity

https://doi.org/10.1002/cbdv.202500940

Cracking the Sulfur Code: Garlic Bioactive Molecules as Multi-Target Blueprints for Drug Discovery

Pharmaceuticals

https://doi.org/10.3390/ph18111766

DFT, Molecular Docking and In-Silico ADME Studies of 2-(2-(4-Chlorophenyl)Benzo[D]-Oxazol-5-Yl)Propanoic Acid Compound

Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi

https://doi.org/10.65520/erciyesfen.1791980

The published articles in The Black Sea Journal of Sciences are licensed under Creative Commons Attribution-NonCommercial 4.0 International