New Adenosine Derivatives from Aizoon canariense L.: In Vitro Anticholinesterase, Antimicrobial, and Cytotoxic Evaluation of Its Extracts
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemical Characterization
2.2. Determination of the Lipoidal Matter
2.3. Biological Activities
2.3.1. In Vitro Cytotoxic Activity
2.3.2. Antimicrobial Activity
2.3.3. Anticholinesterase Activity
3. Experimental
3.1. Plant Material
3.2. General Experimental Procedures
3.3. Extraction and Isolation
3.4. Determination of Lipoidal Matter
3.5. Cell Culture
3.6. Screening of Cytotoxic Activity
3.7. Determination of Antimicrobial Activity
3.8. Anticholinesterase Activity
3.9. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Bibi Sadeer, N.; Llorent-Martínez, E.J.; Bene, K.; Fawzi Mahomoodally, M.; Mollica, A.; Ibrahime Sinan, K.; Stefanucci, A.; Ruiz-Riaguas, A.; Fernández-de Córdova, M.L.; Zengin, G. Chemical profiling, antioxidant, enzyme inhibitory and molecular modelling studies on the leaves and stem bark extracts of three African medicinal plants. J. Pharm. Biomed. Anal. 2019, 174, 19–33. [Google Scholar] [CrossRef] [PubMed]
- Mahomoodally, M.F.; Picot-Allain, C.; Hosenally, M.; Ugurlu, A.; Mollica, A.; Stefanucci, A.; Llorent-Martínez, E.J.; Baloglu, M.C.; Zengin, G. Multi-targeted potential of Pittosporum senacia Putt.: HPLC-ESI-MSn analysis, in silico docking, DNA protection, antimicrobial, enzyme inhibition, anti-cancer and apoptotic activity. Comput. Biol. Chem. 2019, 83, 107114. [Google Scholar] [CrossRef]
- Elgindi, M.R.; Elgindi, O.; Mabry, T. Flavonoids of Aptenia cordifolia. Asian J. Chem. 1999, 11, 1525–1527. [Google Scholar]
- DellaGreca, M.; Di Marino, C.; Previtera, L.; Purcaro, R.; Zarrelli, A. Apteniols A-F, oxyneolignans from the leaves of Aptenia cordifolia. Tetrahedron 2005, 61, 11924–11929. [Google Scholar] [CrossRef]
- Kokpol, U.; Wannachet-isara, N.; Tip-pyang, S.; Chavasiri, W.; Veerachato, G.; Simpson, J.; Weavers, R.T. A c-methylflavone from Trianthema portulacastrum. Phytochemistry 1997, 44, 719–722. [Google Scholar] [CrossRef]
- Sarker, S.D.; Šik, V.; Dinan, L. Isoamericanin A: A neolignan from Trianthema turgidifolia. Biochem. Syst. Ecol. 1998, 26, 681–683. [Google Scholar] [CrossRef]
- Gericke, N.; Viljoen, A.M. Sceletium—A review update. J. Ethnopharmacol. 2008, 119, 653–663. [Google Scholar] [CrossRef]
- Patterson, G.W.; Xu, S. Sterol composition in five families of the order Caryophyllales. Phytochemistry 1990, 29, 3539–3541. [Google Scholar] [CrossRef]
- Jeffs, P.W.; Capps, T.M.; Redfearn, R. Sceletium Alkaloids. Structures of Five New Bases from Sceletium namaquense. J. Org. Chem. 1982, 47, 3611–3617. [Google Scholar] [CrossRef]
- Boulos, L. Flora of Egypt: Checklist; Al Hadara Pub: Cairo, Egypt, 2009; ISBN 9789774760020. [Google Scholar]
- Klak, C.; Hanáček, P.; Bruyns, P.V. Out of southern Africa: Origin, biogeography and age of the Aizooideae (Aizoaceae). Mol. Phylogenet. Evol. 2017, 109, 203–216. [Google Scholar] [CrossRef]
- Al-Laith, A.A.; Alkhuzai, J.; Freije, A. Assessment of antioxidant activities of three wild medicinal plants from Bahrain. Arab. J. Chem. 2015. [Google Scholar] [CrossRef] [Green Version]
- Phoboo, S.; Shetty, K.; ElObeid, T. In vitro assays of anti-diabetic and anti- hypertensive potential of some traditional edible plants of Qatar. J. Med. Act. Plants 2015, 4, 22–29. [Google Scholar] [CrossRef]
- Freije, A.; Alkhuzai, J.; Al-Laith, A.A. Fatty acid composition of three medicinal plants from Bahrain: New potential sources of γ-linolenic acid and dihomo-γ-linolenic. Ind. Crops Prod. 2013, 43, 218–224. [Google Scholar] [CrossRef]
- Abuzaid, H.; Amin, E.; Moawad, A.; Abdelmohsen, U.R.; Hetta, M.; Mohammed, R. Liquid chromatography high-resolution mass spectrometry analysis, phytochemical and biological study of two Aizoaceae plants: A new kaempferol derivative from Trianthema portulacastrum L. Pharmacogn. Res. 2020, 12, 212. [Google Scholar] [CrossRef]
- El-Amier, Y.A.; Haroun, S.A.; El-Shehaby, O.A.; Al-hadithy, O.N. Antioxidant and antimicrobial properties of some wild Aizoaceae species growing in Egyptian desert. J. Environ. Sci. 2016, 45, 1–10. [Google Scholar]
- Ferlay, J.; Ervik, M.; Lam, M.; Colombet, M.; Mery, L.; Piñeros, M.; Znaor, A.; Soerjomataram, I.; Bray, F. Global Cancer Observatory. Available online: https://gco.iarc.fr/ (accessed on 22 September 2019).
- Habli, Z.; Toumieh, G.; Fatfat, M.; Rahal, O.N.; Gali-Muhtasib, H. Emerging cytotoxic alkaloids in the battle against cancer: Overview of molecular mechanisms. Molecules 2017, 22, 250. [Google Scholar] [CrossRef] [PubMed]
- Rahman, M.; Sarker, S.D. Antimicrobial natural products. In Annual Reports in Medicinal Chemistry; Academic Press: Cambridge, MA, USA, 2020; Volume 55, pp. 77–113. ISBN 9780128210192. [Google Scholar]
- Durand, G.A.; Raoult, D.; Dubourg, G. Antibiotic discovery: History, methods and perspectives. Int. J. Antimicrob. Agents 2019, 53, 371–382. [Google Scholar] [CrossRef] [PubMed]
- Mittal, R.P.; Jaitak, V. Plant derived natural alkaloids as new antimicrobial and adjuvant agents in existing antimicrobial therapy. Curr. Drug Targets 2019, 20. [Google Scholar] [CrossRef]
- Ng, Y.P.; Or, T.C.T.; Ip, N.Y. Plant alkaloids as drug leads for Alzheimer’s disease. Neurochem. Int. 2015, 89, 260–270. [Google Scholar] [CrossRef]
- Ashihara, H.; Stasolla, C.; Fujimura, T.; Crozier, A. Purine salvage in plants. Phytochemistry 2018, 147, 89–124. [Google Scholar] [CrossRef] [PubMed]
- Miao, B.J.; Chen, J.; Shao, J.H.; Xu, X.Q.; Zhao, C.C.; Wang, Y.P. A New Adenine Glycoside from the Flowers of Brassica rapa. Chem. Nat. Compd. 2018, 54, 327–329. [Google Scholar] [CrossRef]
- Ciuffreda, P.; Casati, S.; Manzocohi, A. Spectral assignments and reference data complete1H and 13C NMR spectral assignment of α- And β-adenosine, 2′-deoxyadenosine and their acetate derivatives. Magn. Reson. Chem. 2007, 45, 781–784. [Google Scholar] [CrossRef]
- Periyannan, G.R.; Lawrence, B.A.; Egan, A.E. 1H-NMR spectroscopy-based configurational analysis of mono- and disaccharides and detection of β-glucosidase activity: An undergraduate biochemistry laboratory. J. Chem. Educ. 2015, 92, 1244–1249. [Google Scholar] [CrossRef]
- Efimtseva, E.V.; Kulikova, I.V.; Mikhailov, S.N. Disaccharide nucleosides as an important group of natural compounds. Mol. Biol. 2009, 43, 301–312. [Google Scholar] [CrossRef]
- Sone, H.; Kigoshi, H.; Yamada, K. Aurisides A and B, cytotoxic macrolide glycosides from the Japanese sea hare Dolabella auricularia. J. Org. Chem. 1996, 61, 8956–8960. [Google Scholar] [CrossRef] [PubMed]
- Martín, V.; Fabelo, N.; Santpere, G.; Puig, B.; Marín, R.; Ferrer, I.; Díaz, M. Lipid alterations in lipid rafts from Alzheimer’s disease human brain cortex. J. Alzheimer’s Dis. 2010, 19, 489–502. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hussain, G.; Schmitt, F.; Loeffler, J.P.; de Aguilar, J.L.G. Fatting the brain: A brief of recent research. Front. Cell. Neurosci. 2013, 7, 144. [Google Scholar] [CrossRef] [Green Version]
- Banov, D.; Banov, F.; Bassani, A.S. Case Series: The effectiveness of fatty acids from Pracaxi oil in a topical silicone base for scar and wound therapy. Dermatol. Ther. Heidelb. 2014, 4. [Google Scholar] [CrossRef] [Green Version]
- Yuan, H.; Wang, Q.; Wang, Y.; Xie, C.; Xie, K.; Zhao, X. Effect of docosahexaenoic acid and nervonic acid on the damage of learning and memory abilities in rats induced by 1-bromopropane. Chin. J. Ind. Hyg. Occup. Dis. 2013, 31, 806–810. [Google Scholar]
- Li, Q.; Chen, J.; Yu, X.; Gao, J.M. A mini review of nervonic acid: Source, production, and biological functions. Food Chem. 2019, 301, 125286. [Google Scholar] [CrossRef]
- Pereira, D.M.; Correia-da-Silva, G.; Valentão, P.; Teixeira, N.; Andrade, P.B. Anti-Inflammatory effect of unsaturated fatty acids and ergosta-7,22-dien-3-ol from Marthasterias glacialis: Prevention of CHOP-Mediated ER-stress and NF-κB activation. PLoS ONE 2014, 9, e88341. [Google Scholar] [CrossRef]
- Adam, M.; Elhassan, G.O.M.; Yagi, S.; Senol, F.S.; Orhan, I.E.; Ahmed, A.A.; Efferth, T. In-vitro antioxidant and cytotoxic activities of 18 plants from the Erkowit region, Eastern Sudan. Nat. Prod. Bioprospect. 2018, 8, 97. [Google Scholar] [CrossRef] [Green Version]
- Yadav, E.; Singh, D.; Debnath, B.; Rathee, P.; Yadav, P.; Verma, A. Molecular docking and cognitive impairment attenuating effect of phenolic compound rich fraction of Trianthema portulacastrum in scopolamine induced Alzheimer’s disease like condition. Neurochem. Res. 2019, 44, 1665–1677. [Google Scholar] [CrossRef] [PubMed]
- Chiu, S.; Gericke, N.; Farina-Woodbury, M.; Badmaev, V.; Raheb, H.; Terpstra, K.; Antongiorgi, J.; Bureau, Y.; Cernovsky, Z.; Hou, J.; et al. Proof-of-concept randomized controlled study of cognition effects of the proprietary extract Sceletium tortuosum (Zembrin) targeting phosphodiesterase-4 in cognitively healthy subjects: Implications for Alzheimer’s dementia. Evid. Based Complement. Altern. Med. 2014, 2014, 1–9. [Google Scholar] [CrossRef]
- Zhang, Q.-W.; Lin, L.-G.; Ye, W.-C. Techniques for extraction and isolation of natural products: A comprehensive review. Chin. Med. 2018, 13, 20. [Google Scholar] [CrossRef] [Green Version]
- Paquot, C. Standard Methods for the Analysis of Oils, Fats and Derivatives; Elsevier: Amsterdam, The Netherlands; Pergamon Press: Oxford, UK, 1979. [Google Scholar]
- Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J. Immunol. Methods 1983, 65, 55–63. [Google Scholar] [CrossRef]
- Riyadh, S.M.; Gomha, S.M.; Mahmmoud, E.A.; Elaasser, M.M. Synthesis and anticancer activities of thiazoles, 1,3-thiazines, and thiazolidine using chitosan-grafted-poly(vinylpyridine) as basic catalyst. Chem. Heterocycl. Compd. 2015, 51, 1030–1038. [Google Scholar] [CrossRef]
- Saini, K.R.; Choudhary, S.A.; Joshi, Y.C.; Joshi, P. Solvent free synthesis of chalcones and their antibacterial activities. E-J. Chem. 2005, 2, 224–227. [Google Scholar] [CrossRef] [Green Version]
- Gomha, S.M.; Abbas, I.M.; Elneairy, M.A.A.; Elaasser, M.M.; Mabrouk, B.K.A. Antimicrobial and anticancer evaluation of a novel synthetic tetracyclic system obtained by Dimroth rearrangement. J. Serbian Chem. Soc. 2015, 80, 1251–1264. [Google Scholar] [CrossRef]
- Ahmed, F.; Ghalib, R.; Sasikala, P.; Mueen Ahmed, K. Cholinesterase inhibitors from botanicals. Pharmacogn. Rev. 2013, 7, 121–130. [Google Scholar] [CrossRef] [Green Version]
- Magnotti, R.A.; Eberly, J.P.; Quarm, D.E.; McConnell, R.S. Measurement of acetylcholinesterase in erythrocytes in the field. Clin. Chem. 1987, 33, 1731–1735. [Google Scholar] [CrossRef] [PubMed]
- Ellman, G.L.; Courtney, K.D.; Andres, V.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7. [Google Scholar] [CrossRef]
- Refaey, M.S.; Abdelhamid, R.A.; Elimam, H.; Elshaier, Y.A.M.M.; Ali, A.A.; Orabi, M.A.A. Bioactive constituents from Thunbergia erecta as potential anticholinesterase and anti-ageing agents: Experimental and in silico studies. Bioorg. Chem. 2021, 108, 104643. [Google Scholar] [CrossRef] [PubMed]
- Dhanasekaran, S.; Perumal, P.; Palayan, M. In-vitro Screening for acetylcholinesterase enzyme inhibition potential and antioxidant activity of extracts of Ipomoea aquatica Forsk: Therapeutic lead for Alzheimer’s disease. J. Appl. Pharm. Sci. 2015, 5, 12–16. [Google Scholar] [CrossRef] [Green Version]
Compound No. | Compound 1 | Compound 2 | Compound 3 | Compound 4 | Compound 5 | ||||
---|---|---|---|---|---|---|---|---|---|
Position | δH [m, J (Hz)] | δH [m, J (Hz)] | δC | δH [m, J (Hz)] | δC | δH [m, J (Hz)] | δC | δH [m, J (Hz)] | δC |
2 | 7.67–7.73 | 8.76 s | 152 | 8.50 | 156 | - | 134 | 8.5 s | 143 |
4 | - | - | 150 | - | 143 | - | 130 | - | 152 |
4a | - | - | - | - | - | - | - | - | - |
5 | - | - | 121 | - | 140 | - | 128 | - | 120 |
6 | - | - | 156 | - | 157 | - | 134 | - | 157 |
8 | 7.67–7.73 | 8.58 s | 140 | 8.42 (d, 5.28) | 141 | 7.70 (d, 6.92) | 129 | 7.97 s | 140 |
NH2 | - | 5.67 s | - | 7.8 (NH) | - | 5.32 | - | 5.44 s | - |
1′ | 4.13–4.15 (q, 3.52, 5.56, Hz) | 4.01–4.05 (t, J = 8.0 Hz) | 79 | 4.56–4.59 (t, 5.12, 10.68 Hz) | 60–73 | 4.11–4.14 (t, 9.88 Hz) | 60–73 | - | - |
2′ | 3.4–3.51 | 3.0–3.6 | 3.48–3.51 | 3.34–3.57 | - | - | |||
3′ | 73 | - | - | ||||||
4′ | 82 | - | - | ||||||
5′ | 62 | - | - | ||||||
2′,3′-OH | - | - | - | - | - | 2.26 | - | - | - |
2′,3′-OCOCH3 | 3.4–3.51 | 2.05 s | 174–177, 25.39–31.69 | 2.48–2.59 | 20.29–21.56– 177 | - | - | - | - |
1″ | 4.13–4.15 (q, 3.52, 5.56, Hz) | 4.56–4.59 (t, 5.12 Hz, 10.68 Hz) | 60–73 | 4.11–4.14 (t, 3.8 Hz) | 60–73 | - | - | ||
2″ | 3.4–3.51 | 7.23 | 116 | 3.41–3.51 | 3.34–3.57 | - | - | - | |
3″ | 7.42 | 120 | - | - | |||||
4″ | - | 156 | - | - | |||||
5″ | 7.42 | 120 | - | - | |||||
6″ | 1.24–1.35 | 7.23 | 116 | 1.23 | 17.87 | 1.23 | 14 | - | - |
3″,4″,5″-OCH3 | 3.4–3.51 | - | - | 3.48–3.51 | 70 | 3.51 s | 70 | - | - |
1’’’ | 3.4–3.51 | 3.65 | 59.84 | 3.41–3.51 | 66 | 3.34–3.57 | 67 | 3.17 | 49.15 |
2’’’ | 1.62–1.63 | 2.88 s | 50.52 | 1.72–1.73 | 20–30 | 2.00 | 22–33 | 1.16–1.28 | 31.18 |
3‴ | 1.24–1.35 | - | 206 | 1.21–1.24 | 1.21 | 29 | |||
4‴ | 2.11 s | 48.99 | 25 | ||||||
5‴ | 1.29 br.s | 25.13–32.0 | 26 | ||||||
6‴ | 26 | ||||||||
7‴ | 2.47 | 12.24–32.0 | |||||||
8‴ | 1.16–1.28 | ||||||||
9‴ | 1.21–1.23 d | 1.76 | |||||||
10‴ | - | 20.82 | 0.84 | 14.37 | 1.84 | ||||
11‴ | - | - | 1.24 | 0.83 m | |||||
12‴ | 1.62–1.63 | - | - | - | - | 0.83 | 11 | 0.89 m | |
13‴ | 0.86–0.90 | - | - | - | - | 2.47 s | |||
14‴ | - | - | - | - | - | - | 2.36 d | ||
15‴ | - | - | - | - | - | - | 2.36 d |
Retention Time | Fatty Acid | Type | Percentage |
---|---|---|---|
20.8 | Pentadecanoic acid (C15:0) | Saturated | 1.91% |
21.12 | Cis-10-Pentadecenoic acid (C15:1) | Unsaturated | 0.55% |
23.936 | Heptadecanoic acid (margaric acid, C17) | Saturated | 0.72% |
37.24 | Cis-11-Eicosenoic acid (gondoic acid, C20:1) | Unsaturated | 7.39% |
43.20 | Docosanoic acid (Behenic acid, C22:0) | Saturated | 28.30% |
47.01 | Tricosanoic acid (Tricosylic acid, C23:0) | Saturated | 43.08% |
49.14 | Tetracosanoic (Lignoceric acid, C24:0) | Saturated | 0.76% |
52.03 | Nervonic acid (C24:1) | Unsaturated | 8.94% |
Saturated fatty acids | 74.8% | ||
Unsaturated fatty acids | 16.9% |
Sample | AChE Inhibitory Effect IC50 (ng/mL) | HCT-116 IC50 µg/mL | MCF-7 IC50 µg/mL | HepG-2 IC50 µg/mL |
---|---|---|---|---|
Alkaloid fraction | 183.43 ± 38.98 | 14.40 ± 0.8 | 28.00 ± 1.2 | 21.00 ± 0.4 |
Aqueous alkaloid fraction | 139.27 ± 21.40 | |||
Methanolic extract | 112.24 ± 7.73 | 21.20 ± 0.6 | 40.50 ± 3.1 | 26.40 ± 0.3 |
Dichloromethane | 62.48 ± 1.31 | |||
Tacrine | 27.29 ± 0.49 | |||
Doxorubicin | 0.23 ± 0.17 | 0.42 ± 0.35 | 0.46 ± 0.2 |
Tested M.O | Aizoon canariense L. Alkaloid | Aizoon canariense L. MeOH | Control |
---|---|---|---|
Fungi | Ketoconazole | ||
Aspergillus flavus (RCMB 002002) | NA | 16 ± 1.5 *** | 16 ± 1.5 *** |
Candida albicans (RCMB 005003, ATCC) | 16 ± 2 ** | 12 ± 1.0 ** | 20 ± 1.5 *** |
Gram-Positive Bacteria | Gentamycin | ||
Staphylococcus aureus (RCMB 010010) | 13 ± 1.5 ** | 15 ± 1.0 ** | 24 ± 2.0 *** |
Bacillus subtilis (RCMB 015, NRRL B-543) | 14 ± 2 ** | 13 ± 1.5 ** | 26 ± 2 *** |
Gram-Negative Bacteria | Gentamycin | ||
Salmonella typhimurium (RCMB 006, ATCC 14028) | 15 ± 2.0 ** | 13 ± 1.5 ** | 17 ± 1.5 *** |
Escherichia coli (RCMB 010052, ATCC25955) | 16 ± 1.5 *** | 18 ± 2.0 *** | 30 ± 2.0 *** |
Tested Micro-Organism | Tested Extract | ||
---|---|---|---|
A. canariense L. Alkaloid | A. canariense L. MeOH | Standard | |
FUNGI | Amphotericin B | ||
Aspergillus flavus (RCMB 002002) | NA | 1250 | 0.98 |
Candida albicans (RCMB 005003, ATCC) | 625 | 2500 | 0.49 |
Gram-Positive Bacteria | Ampicillin | ||
Staphylococcus aureus (RCMB 010010) | 1250 | 625 | 0.49 |
Bacillus subtilis (RCMB 015, NRRL B-543) | 2500 | 625 | 0.49 |
Gram-Negative Bacteria | Gentamicin | ||
Salmonella typhimurium (RCMB 006, ATCC 14028) | 1250 | 2500 | 0.98 |
Escherichia coli (RCMB 010052, ATCC25955) | 312.5 | 622 | 3.9 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bakr, R.O.; El-Behairy, M.F.; Elissawy, A.M.; Elimam, H.; Fayed, M.A.A. New Adenosine Derivatives from Aizoon canariense L.: In Vitro Anticholinesterase, Antimicrobial, and Cytotoxic Evaluation of Its Extracts. Molecules 2021, 26, 1198. https://doi.org/10.3390/molecules26051198
Bakr RO, El-Behairy MF, Elissawy AM, Elimam H, Fayed MAA. New Adenosine Derivatives from Aizoon canariense L.: In Vitro Anticholinesterase, Antimicrobial, and Cytotoxic Evaluation of Its Extracts. Molecules. 2021; 26(5):1198. https://doi.org/10.3390/molecules26051198
Chicago/Turabian StyleBakr, Riham O., Mohammed F. El-Behairy, Ahmed M. Elissawy, Hanan Elimam, and Marwa A. A. Fayed. 2021. "New Adenosine Derivatives from Aizoon canariense L.: In Vitro Anticholinesterase, Antimicrobial, and Cytotoxic Evaluation of Its Extracts" Molecules 26, no. 5: 1198. https://doi.org/10.3390/molecules26051198