Bioactivity Profile of the Diterpene Isosteviol and its Derivatives
Abstract
:1. Introduction
2. Chemistry of Stevia Glycosides
3. Plant Growth Regulator
4. Pharmacological Activities of Isosteviol Derivatives
4.1. Cytotoxic Agents
4.2. DNA Polymerase and DNA Topoisomerase Inhibitors
4.3. Antiviral Agents
Early Antigen Activation of Epstein–Barr Virus (EBV-EA)
4.4. Antibacterial Agents
Anti-Tuberculosis Agents
4.5. Antihypertensive Agent and Cardio Protection
4.6. Neuroprotective Effect
4.7. Antagonists of Angiotensin II
4.8. Anti-Inflammatory Activity
4.9. Anti-Hyperglycemia Effect
4.9.1. Glucose Receptor Sensitization
4.9.2. α-Glucosidase Inhibitor
5. Other Miscellaneous Uses
5.1. Chiral Catalyst
5.2. Anti-Arsenic Contaminator
6. Conclusions
Funding
Conflicts of Interest
References
- Lohoelter, C.; Weckbecker, M.; Waldvogel, S.R. (−)-isosteviol as a versatile ex-chiral-pool building block for organic chemistry. Eur. J. Org. Chem. 2013, 2013, 5539–5554. [Google Scholar] [CrossRef]
- Lohoelter, C.; Schollmeyer, D.; Waldvogel, S.R. Derivatives of (−)-isosteviol with expanded ring D and various oxygen functionalities. Eur. J. Org. Chem. 2012, 2012, 6364–6371. [Google Scholar] [CrossRef]
- Chen, X.; Hermansen, K.; ** world: Model-based regional estimates. Bull. World Health Organ. 1999, 77, 801–807. [Google Scholar] [CrossRef]
- Simonsen, L.; Kane, A.; Lloyd, J.; Zaffran, M.; Kane, M. Unsafe injections in the develo** world and transmission of bloodborne pathogens: A review. Bull. World Health Organ. 1999. [Google Scholar] [CrossRef]
- Shepard, C.W.; Simard, E.P.; Finelli, L.; Fiore, A.E.; Bell, B.P. Hepatitis B Virus Infection: Epidemiology and Vaccination. Epidemiol. Rev. 2006. [Google Scholar] [CrossRef] [PubMed]
- Gish, R.G. Current treatment and future directions in the management of chronic hepatitis B viral infection. Clin. Liver Dis. 2005. [Google Scholar] [CrossRef] [PubMed]
- Iavarone, M.; Colombo, M. Management of hepatocellular carcinoma. In Viral Hepatitis, 4th ed.; John Wiley & Sons, Ltd.: Hoboken, NJ, USA, 2013; ISBN 9781118637272. [Google Scholar]
- Liu, C.J.; Yu, S.L.; Liu, Y.P.; Dai, X.J.; Wu, Y.; Li, R.J.; Tao, J.C. Synthesis, cytotoxic activity evaluation and HQSAR study of novel isosteviol derivatives as potential anticancer agents. Eur. J. Med. Chem. 2016, 115, 26–40. [Google Scholar] [CrossRef]
- Huang, T.J.; Chou, B.-H.; Lin, C.-W.; Weng, J.H.; Chou, C.-H.; Yang, L.M.; Lin, S.-J. Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus. Phytochemistry 2014, 99, 107–114. [Google Scholar] [CrossRef] [PubMed]
- Huang, T.J.; Yang, C.L.; Kuo, Y.C.; Chang, Y.C.; Yang, L.M.; Chou, B.H.; Lin, S.J. Synthesis and anti-hepatitis B virus activity of C4 amide-substituted isosteviol derivatives. Bioorg. Med. Chem. 2015, 23, 720–728. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, S.; Shibukawa, K.; Hamada, Y.; Kuruma, T.; Kawabata, A.; Masuyama, A. Syntheses of (−)-Tripterifordin and (−)-Neotripterifordin from Stevioside. J. Org. Chem. 2018, 83, 1606–1613. [Google Scholar] [CrossRef]
- Baliga, M.S.; Katiyar, S.K. Chemoprevention of photocarcinogenesis by selected dietary botanicals. Photochem. Photobiol. Sci. 2006. [Google Scholar] [CrossRef]
- Balunas, M.J.; Kinghorn, A.D. Drug discovery from medicinal plants. Life Sci. 2005, 78, 431–441. [Google Scholar] [CrossRef] [PubMed]
- Rocha, S.; Generalov, R.; Pereira, M.D.C.; Peres, I.; Juzenas, P.; Coelho, M.A.N. Epigallocatechin gallate-loaded polysaccharide nanoparticles for prostate cancer chemoprevention. Nanomedicine (Lond). 2011, 6, 79–87. [Google Scholar] [CrossRef] [PubMed]
- Surh, Y.J. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 2003. [Google Scholar] [CrossRef]
- Chatterjee, S.; Biswas, G.; Basu, S.K.; Acharya, K. Antineoplastic effect of mushrooms: A review. Aust. J. Crop Sci. 2011, 5, 904–911. [Google Scholar]
- Gupta, E.; Purwar, S.; Sundaram, S.; Rai, G.K. Nutritional and therapeutic values of Stevia rebaudiana: A review. Acad. J. 2013. [Google Scholar] [CrossRef]
- Chang, S.F.; Chou, B.H.; Yang, L.M.; Hsu, F.L.; Lin, W.K.; Ho, Y.; Lin, S.J. Microbial transformation of isosteviol oxime and the inhibitory effects on NF-κB and AP-1 activation in LPS-stimulated macrophages. Bioorg. Med. Chem. 2009, 17, 6348–6353. [Google Scholar] [CrossRef] [PubMed]
- Chou, B.H.; Yang, L.M.; Chang, S.F.; Hsu, F.L.; Lo, C.H.; Lin, W.K.; Wang, L.H.; Liu, P.C.; Lin, S.J. Fungal transformation of isosteviol lactone and its biological evaluation for inhibiting the AP-1 transcription factor. Phytochemistry 2009, 70, 759–764. [Google Scholar] [CrossRef] [PubMed]
- Chou, B.H.; Yang, L.M.; Chang, S.F.; Hsu, F.L.; Lo, C.H.; Liaw, J.H.; Liu, P.C.; Lin, S.J. Microbial transformation of isosteviol lactone and evaluation of the transformation products on androgen response element. J. Nat. Prod. 2008, 71, 602–607. [Google Scholar] [CrossRef] [PubMed]
- Chang, S.F.; Yang, L.M.; Lo, C.H.; Liaw, J.H.; Wang, L.H.; Lin, S.J. Microbial transformation of isosteviol and bioactivities against the glucocorticoid/androgen response elements. J. Nat. Prod. 2008, 71, 87–92. [Google Scholar] [CrossRef]
- Akihisa, T.; Hamasaki, Y.; Tokuda, H.; Ukiya, M.; Kimura, Y.; Nishino, H. Microbial Transformation of Isosteviol and Inhibitory Effects on Epstein-Barr Virus Activation of the Transformation Products. J. Nat. Prod. 2004, 67, 407–410. [Google Scholar] [CrossRef]
- Sánchez-Osuna, M.; Cortés, P.; Barbé, J.; Erill, I. Origin of the Mobile Dihydro-Pteroate Synthase Gene Determining Sulfonamide Resistance in Clinical Isolates. Front. Microbiol. 2019, 9, 3332. [Google Scholar] [CrossRef]
- Mayer, C.; Janin, Y.L. Non-quinolone inhibitors of bacterial type IIA topoisomerases: A feat of bioisosterism. Chem. Rev. 2014, 114, 2313–2342. [Google Scholar] [CrossRef]
- Wu, Y.; Liu, C.-J.; Liu, X.; Dai, G.-F.; Du, J.-Y.; Tao, J.-C. Stereoselective Synthesis, Characterization, and Antibacterial Activities of Novel Isosteviol Derivatives with D-Ring Modification. Helv. Chim. Acta 2010, 93, 2052–2069. [Google Scholar] [CrossRef]
- Korochkina, M.G.; Sharipova, R.R.; Strobykina, I.Y.; Lantsova, A.D.; Voloshina, A.D.; Kulik, N.V.; Zobov, V.V.; Kataev, V.E.; Mironov, V.F. Synthesis and antimicrobial and antifungal activity of derivatives of the diterpenoid isosteviol and the glycoside steviolbioside containing onium nitrogen atoms. Pharm. Chem. J. 2011, 44, 597–600. [Google Scholar] [CrossRef]
- Korochkina, M.G.; Babaev, V.M.; Strobykina, I.Y.; Voloshina, A.D.; Kulik, N.V.; Kataev, V.E. Synthesis and antimicrobial activity of several bis-quaternized ammonium derivatives of the diterpenoid isosteviol. Chem. Nat. Compd. 2012, 47, 914–917. [Google Scholar] [CrossRef]
- Garifullin, B.F.; Chestnova, R.V.; Mironov, V.F.; Kataev, V.E. Synthesis and antituberculosis activity of conjugates of the diterpenoid isosteviol and the drug dimephosphon. Chem. Nat. Compd. 2012, 48, 794–798. [Google Scholar] [CrossRef]
- Sharipova, R.R.; Andreeva, O.V.; Garifullin, B.F.; Strobykina, I.Y.; Strobykina, A.S.; Voloshina, A.D.; Kravchenko, M.A.; Kataev, V.E. Synthesis and Antimicrobial and Antituberculosis Activity of the First Conjugates of the Diterpenoid Isosteviol and D-Arabinofuranose. Chem. Nat. Compd. 2018, 54, 92–97. [Google Scholar] [CrossRef]
- Garifullin, B.F.; Strobykina, I.Y.; Mordovskoi, G.G.; Mironov, V.F.; Kataev, V.E. Synthesis and antituberculosis activity of derivatives of the diterpenoid isosteviol with azine, hydrazide, and hydrazone moieties. Chem. Nat. Compd. 2011, 47, 55–58. [Google Scholar] [CrossRef]
- Kataev, V.E.; Khaybullin, R.N.; Garifullin, B.F.; Sharipova, R.R. New Targets for Growth Inhibition of Mycobacterium tuberculosis: Why Do Natural Terpenoids Exhibit Antitubercular Activity? Russ. J. Bioorg. Chem. 2018. [Google Scholar] [CrossRef]
- Kataev, V.E.; Strobykina, I.Y.; Andreeva, O.V.; Garifullin, B.F.; Sharipova, R.R.; Mironov, V.F.; Chestnova, R.V. Synthesis and antituberculosis activity of derivatives of Stevia rebaudiana glycoside steviolbioside and diterpenoid isosteviol containing hydrazone, hydrazide, and pyridinoyl moieties. Russ. J. Bioorg. Chem. 2011, 37, 483–491. [Google Scholar] [CrossRef]
- Kataev, V.E.; Militsina, O.I.; Strobykina, I.Y.; Kovylyaeva, G.I.; Musin, R.Z.; Fedorova, O.V.; Rusinov, G.L.; Zueva, M.N.; Mordovskoi, G.G.; Tolstikov, A.G. Synthesis and anti-tuberculous activity of diesters based on isosteviol and dicarboxylic acids. Pharm. Chem. J. 2006, 40, 473–475. [Google Scholar] [CrossRef]
- Khaybullin, R.N.; Strobykina, I.Y.; Gubskaya, V.P.; Fazleeva, G.M.; Latypov, S.K.; Kataev, V.E. New malonate macrocycle bearing two isosteviol moieties and its adduct with fullerene C60. Mendeleev Commun. 2011, 21, 134–136. [Google Scholar] [CrossRef]
- Garifullin, B.F.; Strobykina, I.Y.; Sharipova, R.R.; Kravchenko, M.A.; Andreeva, O.V.; Bazanova, O.B.; Kataev, V.E. Synthesis and antituberculosis activity of the first macrocyclic glycoterpenoids comprising glucosamine and diterpenoid isosteviol. Carbohydr. Res. 2016, 431, 15–24. [Google Scholar] [CrossRef] [PubMed]
- David, S.; Ordway, D.; Arroz, M.J.; Costa, J.; Delgado, R. Activity against Mycobacterium tuberculosis with concomitant induction of cellular immune responses by a tetraaza-macrocycle with acetate pendant arms. Res. Microbiol. 2001. [Google Scholar] [CrossRef]
- Fields, L.E.; Burt, V.L.; Cutler, J.A.; Hughes, J.; Roccella, E.J.; Sorlie, P. The burden of adult hypertension in the United States 1999 to 2000: A rising tide. Hypertension 2004. [Google Scholar] [CrossRef] [PubMed]
- Hajjar, I.; Kotchen, T.A. Trends in Prevalence, Awareness, Treatment, and Control of Hypertension in the United States, 1988-2000. J. Am. Med. Assoc. 2003. [Google Scholar] [CrossRef] [PubMed]
- Tripathi, D.; Hayes, P.C. Beta-blockers in portal hypertension: New developments and controversies. Liver Int. 2014. [Google Scholar] [CrossRef] [PubMed]
- Bankston, J.R.; Kass, R.S. Molecular determinants of local anesthetic action of beta-blocking drugs: Implications for therapeutic management of long QT syndrome variant 3. J. Mol. Cell. Cardiol. 2010. [Google Scholar] [CrossRef] [PubMed]
- Hirasawa, M.; Pittman, Q.J. Nifedipine facilitates neurotransmitter release independently of calcium channels. Proc. Natl. Acad. Sci. USA 2003. [Google Scholar] [CrossRef]
- Shepherd, G. Treatment of poisoning caused by β-adrenergic and calcium-channel blockers. Am. J. Health Pharm. 2006. [Google Scholar] [CrossRef]
- Engebretsen, K.M.; Kaczmarek, K.M.; Morgan, J.; Holger, J.S. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin. Toxicol. 2011. [Google Scholar] [CrossRef]
- Alomar, M.J. Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm. J. 2014. [Google Scholar] [CrossRef]
- Weinstein, R.S.; Cole, S.; Knaster, H.B.; Dahlbert, T. Beta blocker overdose with propranolol and with atenolol. Ann. Emerg. Med. 1985. [Google Scholar] [CrossRef]
- Barron, T.I.; Connolly, R.M.; Sharp, L.; Bennett, K.; Visvanathan, K. Beta blockers and breast cancer mortality: A population-based study. J. Clin. Oncol. 2011. [Google Scholar] [CrossRef] [PubMed]
- Wong, K.-L.; Yang, H.-Y.; Chan, P.; Cheng, T.-H.; Liu, J.-C.; Hsu, F.-L.; Liu, I.-M.; Cheng, Y.-W.; Cheng, J.-T. Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells. Planta Med. 2004, 70, 108–112. [Google Scholar] [CrossRef] [PubMed]
- Nelson, M.T.; Quayle, J.M. Physiological roles and properties of potassium channels in arterial smooth muscle. Am. J. Physiol. 1995, 268, 799–822. [Google Scholar] [CrossRef] [PubMed]
- Boucherat, O.; Chabot, S.; Antigny, F.; Perros, F.; Provencher, S.; Bonnet, S. Potassium channels in pulmonary arterial hypertension. Eur. Respiratory J. 2015, 46, 1167–1177. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wong, K.L.; Chan, P.; Yang, H.Y.; Hsu, F.L.; Liu, I.M.; Cheng, Y.W.; Cheng, J.T. Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat. Life Sci. 2004, 74, 2379–2387. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.C.; Kao, P.F.; Hsieh, M.H.; Chen, Y.J.; Chan, P. The antihypertensive effect of stevioside derivative isosteviol in spontaneously hypertensive rats. Acta Cardiol. Sin. 2001, 17, 133–140. [Google Scholar]
- Xu, D.; Zhang, S.; Foster, D.; Wang, J. The effects of isosteviol against myocardium injury induced by ischaemia-reperfusion in the isolated guinea pig heart. Clin. Exp. Pharmacol. Physiol. 2007, 34, 488–493. [Google Scholar] [CrossRef]
- Xu, D.; Du, W.; Zhao, L.; Davey, A.K.; Wang, J. The neuroprotective effects of isosteviol against focal cerebral ischemia injury induced by middle cerebral artery occlusion in rats. Planta Med. 2008, 74, 816–821. [Google Scholar] [CrossRef]
- Hu, H.; Sun, X.O.; Tian, F.; Zhang, H.; Liu, Q.; Tan, W. Neuroprotective effects of isosteviol sodium injection on acute focal cerebral ischemia in rats. Oxid. Med. Cell. Longev. 2016, 2016. [Google Scholar] [CrossRef]
- **, H.; Gerber, J.P.; Wang, J.; Ji, M.; Davey, A.K. Oral and i.v. pharmacokinetics of isosteviol in rats as assessed by a new sensitive LC-MS/MS method. J. Pharm. Biomed. Anal. 2008, 48, 986–990. [Google Scholar] [CrossRef] [PubMed]
- Wong, K.L.; Lin, J.W.; Liu, J.C.; Yang, H.Y.; Kao, P.F.; Chen, C.H.; Loh, S.H.; Chiu, W.T.; Cheng, T.H.; Lin, J.G.; et al. Antiproliferative effect of isosteviol on angiotensin-II-treated rat aortic smooth muscle cells. Pharmacology 2006, 76, 163–169. [Google Scholar] [CrossRef] [PubMed]
- Choi, W.J.; Kim, H.J.; Lee, Y.K.; Yang, H.S. Effects of 5-hydroxytryptamine on rocuronium-induced neuromuscular blockade in the rat phrenic nerve-hemidiaphragm preparation. Korean J. Anaesthesiol. 2007, 52, 438–442. [Google Scholar] [CrossRef]
- Wong, K.L.; Wu, K.C.; So, E.C.; Wu, R.S.C.; Cheng, T.H. The anti-oxidative effect of isosteviol on angiotensin-II-induced reactive oxygen species generation in hypertensive injury of aortic smooth muscle cells. Eur. J. Anaesthesiol. 2007, 24, 125. [Google Scholar] [CrossRef]
- Yang, L.M.; Chang, S.F.; Lin, W.K.; Chou, B.H.; Wang, L.H.; Liu, P.C.; Lin, S.J. Oxygenated compounds from the bioconversion of isostevic acid and their inhibition of TNF-α and COX-2 expressions in LPS-stimulated RAW264.7 cells. Phytochemistry 2012. [Google Scholar] [CrossRef]
- Dinarello, C.A. Anti-inflammatory Agents: Present and Future. Cell 2010. [Google Scholar] [CrossRef] [PubMed]
- Ramos-Tovar, E.; Hernández-Aquino, E.; Casas-Grajales, S.B.; Montaño, L.D.; Galindo-Gómez, S.; Camacho, J.; Muriel, P. Stevia prevents acute and chronic liver injury induced by carbon tetrachloride by blocking oxidative stress through Nrf2 upregulation. Oxid. Med. Cell. Longev. 2018, 12. [Google Scholar] [CrossRef]
- Ramos-Tovar, E.; Flores-Beltrán, R.; Galindo-Gómez, S.; Vera-Aguilar, E.; Diaz-Ruiz, A.; Montes, S.; Camacho, J.; Tsutsumi, V.; Muriel, P. Stevia rebaudiana tea prevents experimental cirrhosis via regulation of NF-κB, Nrf2, transforming growth factor beta, Smad7, and hepatic stellate cell activation. Phyther. Res. 2018, 32, 2568–2576. [Google Scholar] [CrossRef]
- Ma, J.; Ma, Z.; Wang, J.; Milne, R.W.; Xu, D.; Davey, A.K.; Evans, A.M. Isosteviol reduces plasma glucose levels in the intravenous glucose tolerance test in Zucker diabetic fatty rats 322. Diabetes Obes. Metab. 2007, 9, 597–599. [Google Scholar] [CrossRef]
- Xu, D.; Xu, M.; Lin, L.; Rao, S.; Wang, J.; Davey, A.K. The effect of isosteviol on hyperglycemia and dyslipidemia induced by lipotoxicity in rats fed with high-fat emulsion. Life Sci. 2012, 90, 30–38. [Google Scholar] [CrossRef]
- Nordentoft, I.; Jeppesen, P.B.; Hong, J.; Abudula, R.; Hermansen, K. Isosteviol increases insulin sensitivity and changes gene expression of key insulin regulatory genes and transcription factors in islets of the diabetic KKAy mouse. Diabetes Obes. MeTab. 2008, 10, 939–949. [Google Scholar] [CrossRef] [PubMed]
- Bertram, H.C.; Jeppesen, P.B.; Hermansen, K. An NMR-based metabonomic investigation on effects of supplementation with isosteviol or soy protein to diabetic KKAy mice. Diabetes Obes. MeTab. 2009, 11, 992–995. [Google Scholar] [CrossRef] [PubMed]
- Moons, N.; De Borggraeve, W.; Dehaen, W. Stevioside and Steviol as Starting Materials in Organic Synthesis. Curr. Org. Chem. 2012, 16, 1986–1995. [Google Scholar] [CrossRef]
- Dinh Ngoc, T.; Moons, N.; Kim, Y.; De Borggraeve, W.; Mashentseva, A.; Andrei, G.; Snoeck, R.; Balzarini, J.; Dehaen, W. Synthesis of triterpenoid triazine derivatives from allobetulone and betulonic acid with biological activities. Bioorg. Med. Chem. 2014. [Google Scholar] [CrossRef] [PubMed]
- Thomas, C.C.; Philipson, L.H. Update on Diabetes Classification. Med. Clin. North Am. 2015, 99, 1–16. [Google Scholar] [CrossRef] [PubMed]
- El-Mesallamy, A.; Mahmoud, S.A.; Elazab, K.M.; Hussein, S.A.M.; Hussein, A.M. Attenuation of metabolic dysfunctions in the skeletal muscles of type 1 diabetic rats by Stevia rebaudiana extracts, via AMPK upregulation and antioxidant activities. Acta Sci. Pol. Technol. Aliment. 2018, 17, 289–297. [Google Scholar] [CrossRef] [PubMed]
- Benalla, W.; Bellahcen, S.; Bnouham, M. Antidiabetic Medicinal Plants as a Source of Alpha Glucosidase Inhibitors. Curr. Diabetes Rev. 2010. [Google Scholar] [CrossRef]
- Van de Laar, F.A.; Lucassen, P.L.; Akkermans, R.P.; Van de Lisdonk, E.H.; Rutten, G.E.; Van Weel, C. Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst. Rev. 2005, 18. [Google Scholar] [CrossRef]
- Wu, Y.; Yang, J.-H.; Dai, G.-F.; Liu, C.-J.; Tian, G.-Q.; Ma, W.-Y.; Tao, J.-C. Stereoselective synthesis of bioactive isosteviol derivatives as alpha-glucosidase inhibitors. Bioorg. Med. Chem. 2009, 17, 1464–1473. [Google Scholar] [CrossRef]
- An, Y.J.; Zhang, Y.X.; Wu, Y.; Liu, Z.M.; Pi, C.; Tao, J.C. Simple amphiphilic isosteviol-proline conjugates as chiral catalysts for the direct asymmetric aldol reaction in the presence of water. Tetrahedron Asymmetry 2010, 21, 688–694. [Google Scholar] [CrossRef]
- An, Y.J.; Wang, C.C.; Xu, Y.Z.; Wang, W.J.; Tao, J.C. Highly enantioselective α-aminoxylation reactions catalyzed by isosteviol-proline conjugates in buffered aqueous media. Catal. Lett. 2011, 141, 1123–1129. [Google Scholar] [CrossRef]
- Liu, Y.-X.; Ma, Z.-W.; Li, Y.-X.; Tao, J.-C. New prolinamides with isosteviol skeleton as efficient organocatalysts for the direct asymmetric aldol reaction. Lett. Org. Chem. 2018. [Google Scholar] [CrossRef]
- An, Y.J.; Wang, C.C.; Liu, Z.P.; Tao, J.C. Isosteviol-proline conjugates as highly efficient amphiphilic organocatalysts for asymmetric three-component Mannich reactions in the presence of water. Helv. Chim. Acta 2012, 95, 43–51. [Google Scholar] [CrossRef]
- An, Y.; Qin, Q.; Wang, C.; Tao, J. Isosteviol-amino acid conjugates as highly efficient organocatalysts for the asymmetric one-pot three-component mannich reactions. Chin. J. Chem. 2011, 29, 1511–1517. [Google Scholar] [CrossRef]
- Ma, Z.W.; Liu, Y.X.; Huo, L.J.; Gao, X.; Tao, J.C. Doubly stereocontrolled asymmetric Michael addition of acetylacetone to nitroolefins promoted by an isosteviol-derived bifunctional thiourea. Tetrahedron Asymmetry 2012, 23, 443–448. [Google Scholar] [CrossRef]
- Song, Z.T.; Zhang, T.; Du, H.L.; Ma, Z.W.; Zhang, C.H.; Tao, J.C. Highly enantioselective michael addition promoted by a new diterpene-derived bifunctional thiourea catalyst: A doubly stereocontrolled approach to chiral succinimide derivatives. Chirality 2014. [Google Scholar] [CrossRef] [PubMed]
- Samadder, A.; Das, J.; Das, S.; Khuda-Bukhsh, A.R. Dihydroxy-isosteviol-methyl-ester, an active biological component of Pulsatilla nigricans, reduces arsenic induced cellular dysfunction in testis of male mice. Environ. Toxicol. Pharmacol. 2012, 34, 743–752. [Google Scholar] [CrossRef] [PubMed]
© 2019 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
Ullah, A.; Munir, S.; Mabkhot, Y.; Badshah, S.L. Bioactivity Profile of the Diterpene Isosteviol and its Derivatives. Molecules 2019, 24, 678. https://doi.org/10.3390/molecules24040678
Ullah A, Munir S, Mabkhot Y, Badshah SL. Bioactivity Profile of the Diterpene Isosteviol and its Derivatives. Molecules. 2019; 24(4):678. https://doi.org/10.3390/molecules24040678
Chicago/Turabian StyleUllah, Asad, Sidra Munir, Yahia Mabkhot, and Syed Lal Badshah. 2019. "Bioactivity Profile of the Diterpene Isosteviol and its Derivatives" Molecules 24, no. 4: 678. https://doi.org/10.3390/molecules24040678