Plant Based Antiamoebic Drugs; Part I. Antiamoebic Activity of Phenanthroindolizidine Alkaloids; Common Structural Determinants of Activity with Emetine

Bhutani, K. K.; Sharma, Gitalee; Ali, Mohd

doi:10.1055/s-2006-962803

Cited by 50 publications

(28 citation statements)

References 13 publications

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“…The leaves of this plant have been used for the treatment of asthma as well as bronchitis, rheumatism and dysentery in India. These alkaloids possesses anticancer [20-24], anti-inflammatory [19,25], anti-ameobicidal [26] and anti-viral [27] activity. Several key metabolic enzymes, including thymidylate synthase [28] and dihydrofolate reductase have been reported as biological targets of tylophorine alkaloids [29].…”

Section: Introductionmentioning

confidence: 99%

Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2–mediated angiogenesis

et al. 2013

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BackgroundAnti-angiogenesis targeting VEGFR2 has been considered as an important strategy for cancer therapy. Tylophorine is known to possess anti-inflammatory and antitumor activity, but its roles in tumor angiogenesis, the key step involved in tumor growth and metastasis, and the involved molecular mechanism is still unknown. Therefore, we examined its anti-angiogenic effects and mechanisms in vitro and in vivo.MethodsWe used tylophorine and analyzed its inhibitory effects on human umbilical vein endothelial cells (HUVEC) in vitro and Ehrlich ascites carcinoma (EAC) tumor in vivo.ResultsTylophorine significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR2 tyrosine kinase activity and its downstream signaling pathways including Akt, Erk and ROS in endothelial cells. Using HUVECs we demonstrated that tylophorine inhibited VEGF-stimulated inflammatory responses including IL-6, IL-8, TNF-α, IFN-γ, MMP-2 and NO secretion. Tylophorine significantly inhibited neovascularization in sponge implant angiogenesis assay and also inhibited tumor angiogenesis and tumor growth in vivo. Molecular docking simulation indicated that tylophorine could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR2 kinase unit.ConclusionTylophorine exerts anti-angiogenesis effects via VEGFR2 signaling pathway thus, may be a viable drug candidate in anti-angiogenesis and anti-cancer therapies.

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Section: Introductionmentioning

confidence: 99%

Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2–mediated angiogenesis

et al. 2013

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“…So far, reported alkaloids from Tylophora hirsuta are 13 a-methylo-hirsutine, tylohersutinine, 13a-methyltylo-hirsutinidine and tylohirsutinidine [8,9]. In 1987, Bhutani et al reported its anti-amoebic activity [10]. Other reported constituents from the aerial parts of the Tylophora hirsuta are Gymnorhizol, and β-sitosterol [11].…”

Section: Introductionmentioning

confidence: 99%

Brine shrimp cytotoxicity of crude methanol extract and antispasmodic activity of α-amyrin acetate from Tylophora hirsuta Wall

Ali

2013

BMC Complement Altern Med

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BackgroundWe have previously reported that aerial parts of Tylophora hirsuta have antispasmodic profile. The current work is an attempt for isolation of pharmacologically active compound(s) that contribute for its antispasmodic activity.MethodsPreliminary phytochemical screening for crude methanol extract of Tylophora hirsuta (Th.Cr) is performed. Brine shrimp cytotoxicity of crude methanol extract is performed. Column chromatography was used for isolation of compounds. Mass spectroscopy, H1 NMR and C13 NMR were used for structural determination of compounds. α-amyrin acetate was tried for possible spasmolytic activity in rabbit’s jejunal preparations and KCl-induced contractions.ResultsTh.Cr tested positive for saponins, alkaloids, flavonoids and terpenoids. Compound 1 was isolated as α-amyrin acetate. Compound 2 was heptaeicosanol. Crude methanol extract tested positive for brine shrimp cytotoxicity with LC50 492.33± 8.08 mg/ml. Compound 1 tested positive for antispasmodic activity on spontaneous rabbits’ jejunum preparations with EC50 (60 ± 2) × 10-5M. The compound also tested positive on KCl induced contractions with EC50 (72 ± 3) × 10-5M.ConclusionsThe present work confirms that α-amyrin acetate is has antispasmodic profile and the relaxant effect may be attributed to α-amyrin acetate which is a major compound.

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“…The biological properties of these alkaloids range from cancer cell growth inhibition ( in vitro and in vivo ) [1, 9–16] and anti-inflammatory [3, 17] activity to anti-ameobicidal [18] and anti-viral [19] activity. A summary of their GI 50 concentrations in various cancer cell lines is given in Table 1.…”

Section: Introductionmentioning

confidence: 99%

Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy

Chemler¹

2009

CBC

132

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The phenanthroindolizidine and phenanthroquinolizidine alkaloids, typified by tylophorine and cryptopleurine, are a family of plant-derived small molecules with significant therapeutic potential. The plant extracts have been used in herbal medicine and the isolated compounds have displayed a range of promising therapeutic activity such as anti-ameobicidal, anti-viral, anti-inflammatory and anti-cancer activity. Despite their therapeutic protential, no compounds in this class have fully passed clinical trials. Drawbacks include low in vivo anti-cancer activity, central nervous system toxicity and low natural availability. A number of biological effects of these compounds, such as protein and nucleic acid synthesis suppression, have been identified, but the specific biomolecular targets have not yet been identified. Significant effort has been expended in the synthesis and structure-activityrelationship (SAR) studies of these compounds with the hope that a new drug will emerge. This review will highlight important contributions to the isolation, synthesis, SAR and mechanism of action of the phenanthroindolizidine and pheanthroquinolizidine alkaloids.

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Plant Based Antiamoebic Drugs; Part I. Antiamoebic Activity of Phenanthroindolizidine Alkaloids; Common Structural Determinants of Activity with Emetine

Cited by 50 publications

References 13 publications

Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2–mediated angiogenesis

Tylophorine, a phenanthraindolizidine alkaloid isolated from Tylophora indica exerts antiangiogenic and antitumor activity by targeting vascular endothelial growth factor receptor 2–mediated angiogenesis

Brine shrimp cytotoxicity of crude methanol extract and antispasmodic activity of α-amyrin acetate from Tylophora hirsuta Wall

Phenanthroindolizidines and Phenanthroquinolizidines: Promising Alkaloids for Anti-Cancer Therapy

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