Phytochemical profiling, molecular docking and ADMET prediction of crude extract of Atriplex nitens Schkuhr for the screening of antioxidant and urease inhibitory

Yunus Başar; Semiha Yenigün; Fatih Gül; Tevfik Ozen; İbrahim Demirtas; Mehmet Hakkı Alma; Süleyman Temel

doi:10.32571/ijct.1389719

Research Article

Phytochemical profiling, molecular docking and ADMET prediction of crude extract of Atriplex nitens Schkuhr for the screening of antioxidant and urease inhibitory

Year 2024, Volume: 8 Issue: 1, 60 - 68, 05.06.2024

Yunus Başar , Semiha Yenigün , Fatih Gül , Tevfik Ozen , İbrahim Demirtas , Mehmet Hakkı Alma , Süleyman Temel

https://doi.org/10.32571/ijct.1389719

Cited By: 4

Abstract

Atriplex nitens Schkuhr (ANS), which grows naturally in arid and semi-arid regions of the world, is highly resistant to drought and salty environments and is used as food and animal feed. This study first performed phytochemical analysis and antioxidant and urease inhibition activities on the obtained methanol crude extract of ANS. The catechin and isoquercitrin were detected as the main compounds according to LC-MS/MS results. Oleic acid methyl ester (31.71%), palmitic acid methyl ester (25.87%), linoleic acid methyl ester (19.61%), and nonacosane (16.81%) were detected in GC-MS/MS analysis of extract. Posphomolybdenum reducing, DPPH˙ scavenging, and urease inhibition activities were found effective at 67.27±23.83, 7.85±0.44 and 6.58±0.48 µg/mL, respectively, of ANS extract. In this investigation, the biological activity and chemical composition of the ANS extract were initially examined. Molecular docking and ADMET prediction were performed on this plant's two most abundant components. It was found that the interaction with urease of isoquercitrin (MolDock score-121.42, binding affinity -8.60, and binding constant 0.62 µM) with urease determined a higher than. These two components have a negligible potential for toxicity. The Boiled Egg plot indicates a significant GIa for catechin. However, isoquercitrin does not exhibit BBB or GLa permeability. It was determined that the main component isoquercitrine may be effective against gastric diseases, and it was supported that it was not observed in the BBB and GLa systems.

Keywords

Atriplex nitens Schkuhr, Antioxidant activity, LC-MS/MS, GC-MS/MS, ADMET, Molecular Docking

Project Number

Project No: YİP0923İ23

References

1. Apak, R., Çekiç, S. D., Üzer, A., Çapanoğlu, E., Çelik, S. E., Bener, M., Durmazel, S., Colorimetric sensors and nanoprobes for characterizing antioxidant and energetic substances. Anal. Methods 2020, 2(44), 5266-5321.
2. Pisoschi, A. M.; Pop, A., The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 2015, 97, 55-74.
3. Anraku, M.; Gebicki, J. M.; Iohara, D.; Tomida, H.; Uekama, K.; Maruyama, T.; Hirayama, F.; Otagiri, M., Antioxidant activities of chitosans and its derivatives in in vitro and in vivo studies. Carbohydr Polym 2018, 199, 141-149.
4. Larson, R. A., The antioxidants of higher plants. Phytochem. 1988, 27, 969-978.
5. Gilbert, H., Basic Concepts in Biochemistry. Mc Graw-Hill Inc. Germany 1982, 81-105
6. Kitchen, D. B.; Decornez, H.; Furr, J. R.; Bajorath, J., Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discov 2004, 3 (11), 935-49.
7. Fan, J.; Fu, A.; Zhang, L., Progress in molecular docking. Quant. Biol. 2019, 7, 83-89.
8. Gleeson, M. P.; Hersey, A.; Hannongbua, S., In-silico ADME models: a general assessment of their utility in drug discovery applications. Curr Top Med Chem 2011, 11 (4), 358-81.
9. Ojha, H.; Sethi, M.; Kakkar, R.; Sharma, M.; Saini, M.; Pathak, M., Chapter 7-Chem-bioinformatic approach for drug discovery: in-silico screening of potential antimalarial compounds. In Chemoinformatics and Bioinformatics in the Pharmaceutical Sciences, Sharma, N.; Ojha, H.; Raghav, P. K.; Goyal, R. k., Eds. Academic Press: 2021; pp 207-243.
10. Baccari, W.; Saidi, I.; Filali, I.; Znati, M.; Tounsi, M.; Ascrizzi, R.; Flamini, G.; Jannet, H. B., The root essential oil from the Tunisian endemic plant Ferula tunetana: Chemical composition, biological evaluation, molecular docking analysis and drug-likeness prediction. Arab. J. Chem. 2023, 105044
11. Tan, M., & Temel, S, Alternatif Yem Bitkileri. Atatürk Üniversitesi, Ziraat Fakültesi, Ders Yayınları Erzurum 2012, No: 246, .
12. Benzarti, M.; Rejeb, K. B.; Debez, A.; Abdelly, C. In Environmental and Economical Opportunities for the Valorisation of the Genus Atriplex: New Insights, 2013.
13. Temel, S.; Keskin, B.; Güner, Z., Change in Forage Quality of Whole Plant, Leaf and Stem According to Sowing and Harvesting Periods in Atriplex Nitens Schkuhr Grown Without Fertilizer. Turk. J. Field Crops 2022, 27.
14. Temel, S.; Akbay Tohumcu, S.; Keskin, B., The Effects of Different Sowing Times on Seed Yield and Some Yield Components of Mountain Spinach Grown in Arid Conditions. Journal of the Institute of Science and Technology 2023, 13, 1394-1404.
15. Acar, R., Özköse, A., & Koç, N., İnvestigation of Alternative Use Potential of Atriplex nitens Schkuhr. Journal of Bahri Dagdas Crop Research, 2017, 6(2), 18-22.
16. Altikat, A., & Alma, M. Hakkı, Application of new hybrid models based on artificial neural networks for modeling pyrolysis yields of Atriplex nitens S. Int. J. Energy Res., 2022, 46(4), 4445-4461.
17. Ksouri, R.; Ksouri, W. M.; Jallali, I.; Debez, A.; Magné, C.; Hiroko, I.; Abdelly, C., Medicinal halophytes: potent source of health promoting biomolecules with medical, nutraceutical and food applications. Crit. Rev. Biotechnol. 2012, 32 (4), 289-326.
18. Grabowska, K.; Pietrzak, W.; Paśko, P.; Sołtys, A.; Galanty, A.; Żmudzki, P.; Nowak, R.; Podolak, I. Antihyaluronidase and Antioxidant Potential of Atriplex sagittata Borkh. in Relation to Phenolic Compounds and Triterpene Saponins Molecules [Online], 2023.
19. Kamal, Z.; Ullah, F.; Ayaz, M.; Sadiq, A.; Ahmad, S.; Zeb, A.; Hussain, A.; Imran, M., Anticholinesterase and antioxidant investigations of crude extracts, subsequent fractions, saponins and flavonoids of atriplex laciniata L.: potential effectiveness in Alzheimer's and other neurological disorders. Biol Res 2015, 48 (1), 21.
20. Slama, K.; Boumendjel, M.; Taibi, F.; Boumendjel, A.; Messarah, M., Atriplex halimus aqueous extract abrogates carbon tetrachloride-induced hepatotoxicity by modulating biochemical and histological changes in rats. Arch Physiol Biochem 2020, 126 (1), 49-60.
21. Zohra, T.; Ovais, M.; Khalil, A. T.; Qasim, M.; Ayaz, M.; Shinwari, Z. K.; Ahmad, S.; Zahoor, M., Bio-guided profiling and HPLC-DAD finger printing of Atriplex lasiantha Boiss. BMC Complement. Altern. Med. 2019, 19 (1), 4.
22. Bouaziz, S.; Amri, M.; Taibi, N.; Zeghir-Bouteldja, R.; Benkhaled, A.; Mezioug, D.; Touil-Boukoffa, C., Protoscolicidal activity of Atriplex halimus leaves extract against Echinococcus granulosus protoscoleces. Exp Parasitol 2021, 229, 108155.
23. Siddiqui, B.; Ahmed, S.; Uddin, G.; Khan, M., Triterpenoids of Atriplex stocksii. Phytochem. 1994, 37, 1123-1125.
24. Ben nejma, A.; Nguir, A.; Ben Jannet, H.; Hamza, A.; Adam, D.; Othman, M.; Lawson, A., Phytochemical and Biological Studies of Secondary Metabolites Isolated From Atriplex Inflata L. J. Pharm. Pharmacol. 2017, 69 (8), 1064-1074.
25. Ali, B.; Tabassum, R.; Riaz, N.; Yaqoob, A.; Khatoon, T.; Tareen, R. B.; Jabbar, A.; Nasim, F. U.; Saleem, M., Bioactive triterpenoids from Atriplex lasiantha. J Asian Nat Prod Res 2015, 17 (8), 843-50.
26. Golmakani, E.; Mohammadi, A.; Sani, T. A.; Kamali, H., Phenolic and flavonoid content and antioxidants capacity of pressurized liquid extraction and perculation method from roots of Scutellaria pinnatifida A. Hamilt. subsp alpina (Bornm) Rech. f. The Journal of Supercritical Fluids 2014, 95, 318-324.
27. Başar, Y.; Yenigün, S.; İpek, Y.; Behçet, L.; Gül, F.; Özen, T.; Demirtaş, İ., DNA protection, molecular docking, enzyme inhibition and enzyme kinetic studies of 1,5,9-epideoxyloganic acid isolated from Nepeta aristata with bio-guided fractionation. J. Biomol. Struct. Dyn. 2023, 1-14.
28. Mohamed, R.; Pineda, M.; Aguilar, M., Antioxidant capacity of extracts from wild and crop plants of the Mediterranean region. J. Food Sci. 2007, 72 (1), S059-S063.
29. Blois, M. S., Antioxidant determinations by the use of a stable free radical. Nature 1958, 181 (4617), 1199-1200.
30. Zhang, L.; Mulrooney, S. B.; Leung, A. F.; Zeng, Y.; Ko, B. B.; Hausinger, R. P.; Sun, H., Inhibition of urease by bismuth (III): implications for the mechanism of action of bismuth drugs. Biometals 2006, 19 (5), 503-511.
31. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E., The protein data bank. Nucleic Acids Research 2000, 28 (1), 235-242.
32. Alyar, S.; Özmen, Ü. Ö.; Adem, Ş.; Alyar, H.; Bilen, E.; Kaya, K., Synthesis, spectroscopic characterizations, carbonic anhydrase II inhibitory activity, anticancer activity and docking studies of new Schiff bases of sulfa drugs. J. Mol. Struct. 2021, 1223, 128911.
33. Thomsen, R.; Christensen, M. H., MolDock: A New Technique for High-Accuracy Molecular Docking. J. Med. Chem. 2006, 49 (11), 3315-3321.
34. Yenigün, S.; Başar, Y.; İpek, Y.; Behçet, L.; Özen, T.; Demirtaş, İ., Determination of antioxidant, DNA protection, enzyme inhibition potential and molecular docking studies of a biomarker ursolic acid in Nepeta species. J. Biomol. Struct. Dyn. 2023, 1-18.
35. Yenigun, S.; Ipek, Y.; Marah, S.; Demirtas, I.; Ozen, T., DNA protection, molecular docking, antioxidant, antibacterial, enzyme inhibition, and enzyme kinetic studies for parietin, isolated from Xanthoria parietina (L.) Th. Fr. J. Biomol. Struct. Dyn. 2023, 1-15.
36. Bruna, F.; Fernandez, K.; Urrejola, F.; Touma, J.; Navarro, M.; Sepulveda, B.; Larrazabal-Fuentes, M.; Paredes, A.; Neira, I.; Ferrando, M., Chemical composition, antioxidant, antimicrobial and antiproliferative activity of Laureliopsis philippiana essential oil of Chile, study in vitro and in silico. Arab. J. Chem. 2022, 15 (12), 104271.
37. Horchani, M.; Heise, N. V.; Csuk, R.; Ben Jannet, H.; Harrath, A. H.; Romdhane, A., Synthesis and In Silico Docking Study towards M-Pro of Novel Heterocyclic Compounds Derived from Pyrazolopyrimidinone as Putative SARS-CoV-2 Inhibitors. Molecules 2022, 27 (16), 5303.
38. Ye, Z.; Yang, Y.; Li, X.; Cao, D.; Ouyang, D., An integrated transfer learning and multitask learning approach for pharmacokinetic parameter prediction. Mol. Pharmaceutics. 2018, 16 (2), 533-541.
39. Saidi, I.; Manachou, M.; Znati, M.; Bouajila, J.; Jannet, H. B., Synthesis of new halogenated flavonoid-based isoxazoles: In vitro and in silico evaluation of α-amylase inhibitory potential, a SAR analysis and DFT studies. J. Mol. Struct. 2022, 1247, 131379.
40. Znati, M.; Bordes, C.; Forquet, V.; Lanteri, P.; Jannet, H. B.; Bouajila, J., Synthesis, molecular properties, anti-inflammatory and anticancer activities of novel 3-hydroxyflavone derivatives. Bioorg. Chem. 2019, 89, 103009.
41. Alminderej, F.; Bakari, S.; Almundarij, T. I.; Snoussi, M.; Aouadi, K.; Kadri, A., Antioxidant activities of a new chemotype of Piper cubeba L. fruit essential oil (Methyleugenol/Eugenol): In silico molecular docking and ADMET studies. Plants 2020, 9 (11), 1534.
42. Assel, A.; Hajlaoui, A.; Lazrag, H.; Manachou, M.; Romdhane, A.; Kraiem, J.; Jannet, H. B., Synthesis of new sulfamate linked 4-hydroxycoumarin conjugates as potent anti-α-amylase agents: In vitro approach coupled with molecular docking, DFT calculation and chemoinformatics prediction. J. Mol. Struct. 2023, 1271, 134020.
43. Srivastava, R., Theoretical studies on the molecular properties, toxicity, and biological efficacy of 21 new chemical entities. ACS omega 2021, 6 (38), 24891-24901.