Login Register Cart 0
Generic placeholder image

Current Organic Chemistry

Editor-in-Chief

ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

NMR Structure Elucidation and Molecular Modeling of Lipoxygenase and Cholinesterase Inhibiting Steroids from Hypericum oblongifolium

Author(s): Anam Sajid, Muhammad Afzal, Arfaa Sajid*, Qaisar Manzoor, Ejaz ahmed, Ahsan Sharif and Samia Younas

Volume 26, Issue 19, 2022

Published on: 23 December, 2022

Page: [1798 - 1806] Pages: 9

DOI: 10.2174/1385272827666221216111557

Price: $65

conference banner
Abstract

Hypericum oblongifolium is a potent source of bioactive constituents. A series of pharmacological properties, ranging from wound healing and antiseptic to antiviral, antiinflammatory, anticancer, and apoptosis-inducing activities have been associated with this plant. The current research project was designed to investigate the new secondary metabolites in H. oblongifolium having excellent pharmaceutical potential. In the present investigation two new cholestane-type steroids, hyperinoate A (1) and hyperinoate B (2) were isolated from a chloroform soluble fraction of the whole plant of H. oblongifolium. Structures of isolated new compounds were elucidated based on spectroscopic data including 1D (1HNMR, 13CNMR) and 2D (HMBC, COSY, NOESY) NMR and mass spectrometry (EIMS, HREIMS) data. After structure elucidation, new compounds were named 6α-hydroxy-14α-methyl Cholestan-3-ylacetate and 6α,25-dihydroxy-14α-methyl Cholestane-3-yl-acetate. Both steroids showed promising inhibitory activity against lipoxygenase (LOX) and acetylcholinesterase (AChE) enzymes. Especially hyperinoate A (1) inhibited the lipoxygenase (LOX) enzyme with IC50 41.7± 0.15 μM whereas Baicalein (positive control) had IC50 2.20 ± 0.04 μM. Similarly, Hyperinoate B (2) (56.3 ± 0.33 μM) showed moderate inhibition compared to Galantamine (positive control) 5.38 ± 0.54 μM. These results were validated with in-silico molecular docking investigations. The binding affinity of hyperinoate A (1) (-9.2 Kcal/mol) against LOX-5(PDB ID 3V99) showed moderate inhibition as compared to baicalein (positive control) (-7.7 Kcal/mol).The binding affinities of hyperinoate B (2) (-10.5 Kcal/mol) were close to galantamine (-10.6 Kcal/mol). All in-vitro and in-silico results revealed that both newly isolated compounds showed moderate inhibition against lipoxygenase (LOX) and acetylcholinesterase (AChE) enzymes.

« Previous Next »
Graphical Abstract

[1]
Orafaie, A.; Mousavian, M.; Orafai, H.; Sadeghian, H. An overview of lipoxygenase inhibitors with approach of in vivo studies. Prostaglandins Lipid Mediat., 2020, 148, 106411-106420.
[http://dx.doi.org/10.1016/j.prostaglandins.2020.106411] [PMID: 31953016]
[2]
Prigge, S.T.; Boyington, J.C.; Faig, M.; Doctor, K.S.; Gaffney, B.J.; Amzel, L.M. Structure and mechanism of lipoxygenases. Biochimie, 1997, 79(11), 629-636.
[http://dx.doi.org/10.1016/S0300-9084(97)83495-5] [PMID: 9479444]
[3]
Kubo, I.; Ha, T.J.; Shimizu, K. Lipoxygenase inhibitory activity of 6-pentadecanylsalicylic acid without prooxidant effect. Nat. Prod. Commun., 2010, 5(1), 1934578X1000500.
[http://dx.doi.org/10.1177/1934578X1000500121] [PMID: 20184028]
[4]
Srivastava, P.; Vyas, V.K.; Variya, B.; Patel, P.; Qureshi, G.; Ghate, M. Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives. Bioorg. Chem., 2016, 67, 130-138.
[http://dx.doi.org/10.1016/j.bioorg.2016.06.004] [PMID: 27376460]
[5]
Lončarić, M.; Strelec, I.; Moslavac, T.; Šubarić, D.; Pavić, V.; Molnar, M. Lipoxygenase inhibition by plant extracts. Biomolecules, 2021, 11(2), 152-170.
[http://dx.doi.org/10.3390/biom11020152] [PMID: 33503885]
[6]
Adewusi, E.A.; Moodley, N.; Steenkamp, V. Medicinal plants with cholinesterase inhibitory activity: A review. Afr. J. Biotechnol., 2010, 9, 8257-8276.
[7]
Tundis, R.; Bonesi, M.; Menichini, F.; Loizzo, M.R. Recent Knowledge on Medicinal Plants as Source of Cholinesterase Inhibitors for the Treatment of Dementia. Mini Rev. Med. Chem., 2016, 16(8), 605-618.
[http://dx.doi.org/10.2174/1389557515666150709104731] [PMID: 26156548]
[8]
Pohanka, M. Inhibitors of acetylcholinesterase and butyrylcholinesterase meet immunity. Int. J. Mol. Sci., 2014, 15(6), 9809-9825.
[http://dx.doi.org/10.3390/ijms15069809] [PMID: 24893223]
[9]
Dhivya, P.S.; Sobiya, M.; Selvamani, P.; Latha, S. An approach to alzheimer’s disease treatment with cholinesterase inhibitory activity from various plant species. Int. J. Pharm. Tech. Res., 2014, 6, 1450-1467.
[10]
Raziq, N.; Saeed, M.; Shahid, M.; Muhammad, N.; Khan, H.; Gul, F. Pharmacological basis for the use of Hypericum oblongifolium as a medicinal plant in the management of pain, inflammation and pyrexia. BMC Complement. Altern. Med., 2015, 16(1), 41.
[http://dx.doi.org/10.1186/s12906-016-1018-z] [PMID: 26832937]
[11]
Soumyanath, A. Review of plants with anti-diabetes mellitus properties. J. Nat. Prod., 2018, 81(8), 1916-1920.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00457]
[12]
Sajid, A.; Ahmed, E.; Sharif, A.; Arshed, F.; Arshad, M.; Sher, M.; Sajid, A.; Amanat, S. ‘Bioassay directed isolation studies on Hypericum oblongifolium’. J. Chem. Soc. Pak., 2018, 40, 249-254.
[13]
Ali, M.; Arfan, M.; Zaman, K.; Ahmad, H.; Akbar, N.; Anis, I.; Shah, M.R. ‘Antiproliferative activity and chemical constituents of Hypericum oblongifolium’. J. Chem. Soc. Pak., 2011, 33, 772-777.
[14]
Ali, M.; Latif, A.; Zaman, K.; Arfan, M.; Maitland, D.; Ahmad, H.; Ahmad, M. Anti-ulcer xanthones from the roots of Hypericum oblongifolium Wall. Fitoterapia, 2014, 95, 258-265.
[http://dx.doi.org/10.1016/j.fitote.2014.03.014] [PMID: 24685505]
[15]
Arfan, M.; Ali, M.; Ahmad, H.; Anis, I.; Khan, A.; Choudhary, M.I.; Shah, M.R. Urease inhibitors from Hypericum oblongifolium WALL. J. Enzyme Inhib. Med. Chem., 2010, 25(2), 296-299.
[http://dx.doi.org/10.3109/14756360903179385] [PMID: 20222765]
[16]
Ferheen, S.; Ahmed, E.; Malik, A.; Afza, N.; Lodhi, M.A.; Choudhary, M.I. Hyperinols A and B, chymotrypsin inhibiting triterpenes from Hypericum oblongifolium. Chem. Pharm. Bull. (Tokyo), 2006, 54(8), 1088-1090.
[http://dx.doi.org/10.1248/cpb.54.1088] [PMID: 16880649]
[17]
Obložinský, M.; Bezáková, L.; Holková, I.; Vanko, M.; Kartnig, T.; Pšenák, M. Antilipoxygenase activity of compounds from Hypericum perforatum. Biologia (Bratisl.), 2006, 61(3), 331-332.
[http://dx.doi.org/10.2478/s11756-006-0060-6]
[18]
Hernandez, M.F.; Falé, P.L.V.; Araújo, M.E.M.; Serralheiro, M.L.M. Acetylcholinesterase inhibition and antioxidant activity of the water extracts of several Hypericum species. Food Chem., 2010, 120(4), 1076-1082.
[http://dx.doi.org/10.1016/j.foodchem.2009.11.055]
[19]
Oliveira, A.I.; Pinho, C.; Sarmento, B.; Dias, A.C.P. Neuroprotective activity of Hypericum perforatum and its major components. Front. Plant Sci., 2016, 7, 1004.
[http://dx.doi.org/10.3389/fpls.2016.01004] [PMID: 27462333]
[20]
Czapski, G.A.; Czubowicz, K.; Strosznajder, R.P. Evaluation of the antioxidative properties of lipoxygenase inhibitors. Pharmacol. Rep., 2012, 64(5), 1179-1188.
[http://dx.doi.org/10.1016/S1734-1140(12)70914-3] [PMID: 23238474]
[21]
Araujo, C.R.M.; Santos, V.L.A.; Gonsalves, A.A. Acetylcholinesterase - AChE: A pharmacological interesting enzyme. Rev. Virtual Quim, 2016, 8, 1818-1834.
[http://dx.doi.org/10.21577/1984-6835.20160122]
[22]
Ma, D.L.; Chan, D.S.H.; Leung, C.H. Molecular docking for virtual screening of natural product databases. Chem. Sci. (Camb.), 2011, 2(9), 1656-1665.
[http://dx.doi.org/10.1039/C1SC00152C]
[23]
Egbuna, C.; Kumar, S.; Ifemeje, J.C.; Ezzat, S.M.; Kaliyaperumal, S. Phytochemicals as lead compounds for new drug discovery, 1st ed; Elsevier, 2019.
[24]
Saleem, S.; Muhammad, G.; Hussain, M.A.; Altaf, M.; Bukhari, S.N.A. Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iran. J. Basic Med. Sci., 2020, 23(12), 1501-1526.
[PMID: 33489024]
[25]
Harborne, J.B. Phytochemical method, 1st ed; Toppao Company Ltd.: Tokyo, Japan, 1973.
[26]
Akihisa, A.; Tamura, T.; Matsumoto, T. ‘14α-methyl-5α-ergosta-9(11),24(28)-diene-3β-ol, A sterol from Gynostemma pentaphylum’. Phytochemistry, 1987, 26, 2412-2413.
[http://dx.doi.org/10.1016/S0031-9422(00)84735-4]
[27]
Ahmed, E.; Nawaz, S.A.; Malik, A.; Choudhary, M.I. Isolation and cholinesterase-inhibition studies of sterols from Haloxylon recurvum. Bioorg. Med. Chem. Lett., 2006, 16(3), 573-580.
[http://dx.doi.org/10.1016/j.bmcl.2005.10.042] [PMID: 16274989]
[28]
Yawer, M.A.; Ahmed, E.; Malik, A.; Ashraf, M.; Rasool, M.A.; Afza, N. New Lipoxygenase-Inhibiting Constituents from Calligonum polygonoides. Chem. Biodivers., 2007, 4(7), 1578-1585.
[http://dx.doi.org/10.1002/cbdv.200790137] [PMID: 17638339]
[29]
Kazmi, M.H.; Ahmed, E.; Hameed, S.; Malik, A.; Fatima, I.; Ashraf, M. Cashmirols A and B, new lipoxygenase inhibiting triterpenes from Sorbus cashmiriana. Chem. Biodivers., 2009, 6(9), 1471-1476.
[http://dx.doi.org/10.1002/cbdv.200800213] [PMID: 19774602]
[30]
Arshed, F.; Ahmed, E.; Sharif, A.; Sajid, A.; Arshad, M.; Khalid, H.N.; Razaq, A. ‘Two new lipoxygenase inhibiting constituents from Pervoskia abrotanoides’. J. Chem. Soc. Pak., 2017, 39, 1084-1088.
[31]
Parveen, S.; Saleem, M.; Riaz, N.; Ashraf, M.; Qurat-ul-Ain, M.F.; Nisar, M.F.; Jabbar, A. New norterpenoids and a sphingolipid from Carissa opaca. J. Asian Nat. Prod. Res., 2016, 18(3), 222-231.
[http://dx.doi.org/10.1080/10286020.2015.1064904] [PMID: 27010529]
[32]
Yang, S.; Ma, Q.Y.; Kong, F.D.; Xie, Q.Y.; Huang, S.Z.; Zhou, L.M.; Dai, H.F.; Yu, Z.F.; Zhao, Y.X. Two new compounds from the fruiting bodies of Ganoderma philippii. J. Asian Nat. Prod. Res., 2018, 20(3), 249-254.
[http://dx.doi.org/10.1080/10286020.2017.1326911]
[33]
Jitapunkul, K.; Poachanukoon, O.; Hannongbua, S.; Toochinda, P.; Lawtrakul, L. Simulation Study of Interactions Between Two Bioactive Components from Zingiber cassumunar and 5-Lipoxygenase. Cell. Mol. Bioeng., 2018, 11(1), 77-89.
[http://dx.doi.org/10.1007/s12195-017-0515-6] [PMID: 31719880]
[34]
Tappel, A.I. Method in Enzymology; Academic Press: New York, NY, 1962, Vol. 5, .
[35]
Nawaz, Z.; Ahmed, E.; Sharif, A.; Sajid, A.; Arshed, F.; Arshad, M.; Anjum, M.I.; Razaq, A. Two triterpenyl fatty acid esters from Fagonia cretica as lipoxygenase inhibitors. J. Chem. Soc. Pak., 2018, 40, 406-409.
[36]
Ellman, G.L.; Courtney, K.D.; Andres, V., Jr; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7(2), 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[37]
Gilbert, N.C.; Rui, Z.; Neau, D.B.; Waight, M.T.; Bartlett, S.G.; Boeglin, W.E.; Brash, A.R.; Newcomer, M.E. Conversion of human 5‐lipoxygenase to a 15‐lipoxygenase by a point mutation to mimic phosphorylation at Serine‐663. FASEB J., 2012, 26(8), 3222-3229.
[http://dx.doi.org/10.1096/fj.12-205286] [PMID: 22516296]
[38]
Cheung, J.; Rudolph, M.J.; Burshteyn, F.; Cassidy, M.S.; Gary, E.N.; Love, J.; Franklin, M.C.; Height, J.J. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J. Med. Chem., 2012, 55(22), 10282-10286.
[http://dx.doi.org/10.1021/jm300871x] [PMID: 23035744]
[39]
Al-Khayyat, M.Z.S.; Al-Dabbagh, A.G.A. In silico prediction and docking of tertiary structure of luxi, an inducer synthase of Vibrio fischeri. Rep. Biochem. Mol. Biol., 2016, 4(2), 66-75.
[PMID: 27536699]
[40]
Madeswaran, A.; Umamaheswari, M.; Asokkumar, K.; Sivashanmugam, T.; Subhadradevi, V.; Jagannath, P. Docking studies: In silico lipoxygenase inhibitory activity of some commercially available flavonoids. Bangladesh J. Pharmacol., 2011, 6(2), 133-138.
[http://dx.doi.org/10.3329/bjp.v6i2.9408]
[41]
Ali, M.R.; Sadoqi, M.; Møller, S.G.; Boutajangout, A.; Mezei, M. Assessing the binding of cholinesterase inhibitors by docking and molecular dynamics studies. J. Mol. Graph. Model., 2017, 76, 36-42.
[http://dx.doi.org/10.1016/j.jmgm.2017.06.027] [PMID: 28711758]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy