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Jeffrey S. Johnson - One of the best experts on this subject based on the ideXlab platform.
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De Novo Synthesis of the DEF-Ring Stereotriad Core of the Veratrum Alkaloids
The Journal of organic chemistry, 2020Co-Authors: Matthew A. Horwitz, Jacob G. Robins, Jeffrey S. JohnsonAbstract:The synthesis of the stereotriad core in the eastern portion of the Veratrum alkaloids Jervine (1), cyclopamine (2), and veratramine (3) is reported. Starting from a known β-methyltyrosine derivati...
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Progress toward a Convergent, Asymmetric Synthesis of Jervine
Organic letters, 2020Co-Authors: Blane P. Zavesky, Pedro De Jesus Cruz, Jeffrey S. JohnsonAbstract:Progress toward a convergent approach for the enantioselective synthesis of the Veratrum alkaloid Jervine is presented. The two requisite fragments were stereoselectively and efficiently fashioned ...
Khalid A. El Sayed - One of the best experts on this subject based on the ideXlab platform.
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The Veratrum alkaloids Jervine, veratramine, and their analogues as prostate cancer migration and proliferation inhibitors: biological evaluation and pharmacophore modeling
Medicinal Chemistry Research, 2013Co-Authors: Mohammad A. Khanfar, Khalid A. El SayedAbstract:Veratrum alkaloids are a group of steroidal alkaloids with penta-, hexa-, or heptacyclic C-nor-D-homosteroidal or regular hexacycliccholestane skeleton. Activation of the Hedgehog (Hh) pathway aberrantly associated with numerous malignancies. Cyclopamine blocked Hh pathway by directly binding Smo and slows down the growth of these tumors in various animal models. To less extent, Jervine and the veratrane Veratrum alkaloid veratramine were also reported as possible Hh signaling inhibitors. This encouraged the study of our small library of natural, biocatalytic, and semisynthetic jervane and veratrane alkaloids’ ability to inhibit the growth, proliferation, and migration of the prostate metastatic cancer cell line PC-3 to establish a preliminary structure–activity relationship. Alkaloids possessing C-3-keto functionality with ∆^4,5 or ∆^1,2 and ∆^4,5 exhibited significant enhancement of antiproliferative and antimigratory activities. A common feature pharmacophore model of active Veratrum alkaloids was built and validated using receiver-operating characteristic curve analyses.
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Abstract 4778: Computer-assisted molecular design use for the discovery and optimization of rationally-designed anticancer natural products. Discovery of olive oil-derived oleocanthal as a c-Met inhibitor and optimization of Veratrum alkaloids as Hed
Cancer Research, 2012Co-Authors: Khalid A. El Sayed, Ahmed Y. Elnagar, Mohammad A. KhanfarAbstract:Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Dysregulation of the proto-oncogene receptor tyrosine kinase c-Met, which encodes the high-affinity receptor for hepatocyte growth factor (HGF) and the Hedgehog (Hh) pathway aberrantly associated with numerous malignancies including basal cell carcinoma, medulloblastoma, prostate, pancreatic and breast cancers. The Mediterranean diet is associated with lower incidences of cardiovascular disease, age-related cognitive disease and cancer. (-)-Oleocanthal is a naturally occurring minor secoiridoid from extra-virgin olive oil with potent anti-inflammatory activity via its ability to inhibit COX-1 and COX-2 and anti-Alzheimer's activity. Cyclopamine and its 11-oxo derivative Jervine are C-nor-D-homosteroidal alkaloids with known potent teratogenic effects that induce cyclopic malformations in sheep. The jervane Veratrum alkaloids cyclopamine and Jervine and the veratrane alkaloid veratramine were among the early known natural products that blocked the expression of the Hh pathway targets PTCH1 and GLI1, lowering Bcl2 levels and inducing apoptosis in many tumors. Computer-assisted molecular design (CAMD) identified oleocanthal as a potential virtual c-Met inhibitor hit. Oleocanthal inhibited the proliferation, migration, and invasion of the epithelial human breast and prostate cancer cell lines MCF7, MDA-MB-231, and PC-3, respectively. Oleocanthal demonstrated anti-angiogenic activity and inhibited the phosphorylation of c-Met kinase in vitro. CAMD study of our library of natural, biocatalytic, and semisynthetic jervane and veratrane alkaloids suggested that compounds with C-3-keto functionality with α4,5 or β1,2 and γ4,5 exhibited high virtual Hh binding affinity scores and possible Hh pathway activity. These compounds showed significant ability to inhibit the growth, proliferation, and migration of the prostate metastatic cancer cell line PC-3, which aided the establishment of a preliminary structure-activity relationship. (-)-Oleocanthal and Veratrum alkaloids can have potential therapeutic application for the control of c-Met- and Hh-dependent malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4778. doi:1538-7445.AM2012-4778
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Transformation of Jervine by Cunninghamella elegans ATCC 9245.
Phytochemistry, 2000Co-Authors: Khalid A. El Sayed, Ahmed F. Halim, Ahmed M. Zaghloul, D. Chuck Dunbar, James D. McchesneyAbstract:Abstract Preparative-scale fermentation of the known C- nor -D-homosteroidal jerveratrum alkaloid Jervine with Cunninghamella elegans (ATCC 9245) has resulted in the isolation of (−)-jervinone as the major metabolite. In addition, C. elegans ATCC 9245 was able to epimerize C-3 of Jervine, producing 3- epi -Jervine. This epimerization reaction was similar to that reported for tomatidine, the known spirosolane-type Solanum alkaloid. The structure elucidation of both metabolites was based primarily on 1D- and 2D-NMR analyses.
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A Study of Alkaloids in Veratrum viride Aiton
International Journal of Pharmacognosy, 1996Co-Authors: Khalid A. El Sayed, Ahmed F. Halim, Ahmed M. Zaghloul, James D. Mcchesney, Ik-soo LeeAbstract:The phytochemical study of Veratrum viride (Liliaceae) roots and rhizomes led to the isolation of 5 alkaloids reported for the first time in this species viz. veramarine [1], angeloylzygadenine [4] zygadenine [6], 15-O-methylbutyroylgermine [8], and 1a, 3s-dihydroxy 5a-jervanin-12-en-11-one [9]. The well known alkaloids veratramine [2], Jervine [3], isorubiJervine [5], germine [7], rubiJervine [10], and pseudoJervine [11] were also isolated in the course of this effort. The identification of all compounds was aided significantly by 2D-NMR spectral analyses.
Weidong Zhang - One of the best experts on this subject based on the ideXlab platform.
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Antitumor and antiplatelet activity of alkaloids from veratrum dahuricum.
Phytotherapy research : PTR, 2010Co-Authors: Jian Tang, Run-hui Liu, Yun-heng Shen, Hui-zi Jin, Shi-kai Yan, Xiao-hua Liu, Hua-wu Zeng, Ye-xiong Tan, Weidong ZhangAbstract:Ten steroidal alkaloids – cyclopamine, veratramine, Jervine, 3, 15-diangyloylgermine, 3-angyloylzygadenine, 3-veratroyl zygadenine, 15-veratroylgermine, germine, veratrosine and pseudoJervine – from Veratrum dahuricum, together with the ethanol extract and total alkaloids, were evaluated for their antitumor and antiplatelet activities. Cyclopamine, veratramine and germine significantly inhibited the hedgehog pathway in NIH/3T3 cells. Cyclopamine exerted a potent inhibitory effect against the growth of PANC-1 tumors in mice, with inhibition rates of 40.64%, 44.37%, 46.77% at doses of 5.0, 15.0 and 50.0 mg kg-1, respectively. Veratroylgermine was found to produce the strongest inhibition against the platelet aggregation induced by arachidonic acid, with inhibition rate of 92.0% at 100 μM. Copyright © 2009 John Wiley & Sons, Ltd.
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Antitumor activity of extracts and compounds from the rhizomes of Veratrum dahuricum.
Phytotherapy research : PTR, 2008Co-Authors: Jian Tang, Run-hui Liu, Yun-heng Shen, Hui-zi Jin, Shi-kai Yan, Weidong ZhangAbstract:The antitumor activity of six extracts (ethanol extract, petroleum ether fraction, CHCl(3) fraction, ethyl acetate fraction, n-butanol fraction and total alkaloids) from the rhizomes of Veratrum dahuricum, and six compounds (veratramine (1), Jervine (2), germine (3), veramitaline (4), veratrosine (5) and cyclopamine (6)) from the ethanol extract were investigated in vitro. The 12 samples exhibited cytotoxic activity against human tumor cell lines A549, PANC-1, SW1990 and NCI-H249. Among these samples, CHCl(3) fraction, the total alkaloids, compounds 1 and 6 showed higher inhibitory activity, compound 3 selectively exhibited significant cytotoxicity to SW1990 and NCI-H249.
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Biotransformation of Vermitaline by Cunninghamella echinulata
Helvetica Chimica Acta, 2008Co-Authors: Keyu Chen, Yue-hu Pei, Run-hui Liu, Weidong ZhangAbstract:Biotransformation of Jervine (1) by Cunninghamella echinulata (ACCC 30369) was carried out. Four biotransformation products were obtained, and three of them, 3–5, were identified as new compounds. On the basis of their NMR and mass-spectral data, their structures were characterized as jervinone (2), 7α-hydroxyJervine (3), 14α-hydroxyJervine (4), and 1β,7α-dihydroxyJervine (5). The X-ray diffraction structure of 1 is also reported for the first time.
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Simultaneous Determination of Six Steroidal Alkaloids of Veratrum dahuricum by HPLC–ELSD and HPLC–MSn
Chromatographia, 2007Co-Authors: Jian Tang, Run-hui Liu, Yun-heng Shen, Hui-zi Jin, Shi-kai Yan, Weidong ZhangAbstract:A high performance liquid chromatography coupled with evaporative light scattering detection (HPLC–ELSD) and electrospray ionization multistage mass spectrometry (HPLC–ESI–MSn), respectively, has been performed for the simultaneous determination of six steroidal alkaloids, including pseudoJervine, veratrosine, Jervine, veratramine, 3-veratroylzygadenine, 3-angeloylzygadenine, in Veratrum dahuricum collected in different seasons. The plants were soaked in methanol and extracted ultrasonically. The six steroidal alkaloids were obtained by silica gel column chromatography, eluting with gradient petroleum and acetyl acetate. The intra-day and inter-day precisions of the method were evaluated and were less than 1.4%. The content of steroidal alkaloids in the plant varied significantly from spring to autumn, confirming the necessity to control the quality of V. dahuricum during its preparation and application.
Jian Tang - One of the best experts on this subject based on the ideXlab platform.
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Antitumor and antiplatelet activity of alkaloids from veratrum dahuricum.
Phytotherapy research : PTR, 2010Co-Authors: Jian Tang, Run-hui Liu, Yun-heng Shen, Hui-zi Jin, Shi-kai Yan, Xiao-hua Liu, Hua-wu Zeng, Ye-xiong Tan, Weidong ZhangAbstract:Ten steroidal alkaloids – cyclopamine, veratramine, Jervine, 3, 15-diangyloylgermine, 3-angyloylzygadenine, 3-veratroyl zygadenine, 15-veratroylgermine, germine, veratrosine and pseudoJervine – from Veratrum dahuricum, together with the ethanol extract and total alkaloids, were evaluated for their antitumor and antiplatelet activities. Cyclopamine, veratramine and germine significantly inhibited the hedgehog pathway in NIH/3T3 cells. Cyclopamine exerted a potent inhibitory effect against the growth of PANC-1 tumors in mice, with inhibition rates of 40.64%, 44.37%, 46.77% at doses of 5.0, 15.0 and 50.0 mg kg-1, respectively. Veratroylgermine was found to produce the strongest inhibition against the platelet aggregation induced by arachidonic acid, with inhibition rate of 92.0% at 100 μM. Copyright © 2009 John Wiley & Sons, Ltd.
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Antitumor activity of extracts and compounds from the rhizomes of Veratrum dahuricum.
Phytotherapy research : PTR, 2008Co-Authors: Jian Tang, Run-hui Liu, Yun-heng Shen, Hui-zi Jin, Shi-kai Yan, Weidong ZhangAbstract:The antitumor activity of six extracts (ethanol extract, petroleum ether fraction, CHCl(3) fraction, ethyl acetate fraction, n-butanol fraction and total alkaloids) from the rhizomes of Veratrum dahuricum, and six compounds (veratramine (1), Jervine (2), germine (3), veramitaline (4), veratrosine (5) and cyclopamine (6)) from the ethanol extract were investigated in vitro. The 12 samples exhibited cytotoxic activity against human tumor cell lines A549, PANC-1, SW1990 and NCI-H249. Among these samples, CHCl(3) fraction, the total alkaloids, compounds 1 and 6 showed higher inhibitory activity, compound 3 selectively exhibited significant cytotoxicity to SW1990 and NCI-H249.
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Simultaneous Determination of Six Steroidal Alkaloids of Veratrum dahuricum by HPLC–ELSD and HPLC–MSn
Chromatographia, 2007Co-Authors: Jian Tang, Run-hui Liu, Yun-heng Shen, Hui-zi Jin, Shi-kai Yan, Weidong ZhangAbstract:A high performance liquid chromatography coupled with evaporative light scattering detection (HPLC–ELSD) and electrospray ionization multistage mass spectrometry (HPLC–ESI–MSn), respectively, has been performed for the simultaneous determination of six steroidal alkaloids, including pseudoJervine, veratrosine, Jervine, veratramine, 3-veratroylzygadenine, 3-angeloylzygadenine, in Veratrum dahuricum collected in different seasons. The plants were soaked in methanol and extracted ultrasonically. The six steroidal alkaloids were obtained by silica gel column chromatography, eluting with gradient petroleum and acetyl acetate. The intra-day and inter-day precisions of the method were evaluated and were less than 1.4%. The content of steroidal alkaloids in the plant varied significantly from spring to autumn, confirming the necessity to control the quality of V. dahuricum during its preparation and application.
Sungul Turkoz - One of the best experts on this subject based on the ideXlab platform.
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Alkaloids from Veratrum album
Phytochemistry, 1991Co-Authors: Atta-ur-rahman, Rahat Azhar Ali, Tahira Parveen, M. Iqbal Choudhary, Bilge Sener, Sungul TurkozAbstract:Abstract Leaves of Veratrum album of Turkish origin have yielded two new steroidal alkaloids, O -acetylJervine and methylJervine- N -3′-propanoate along with the known alkaloid Jervine. The structures of these new bases were established on the basis of 2D NMR and other spectroscopic techniques.