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Junxi Liu - One of the best experts on this subject based on the ideXlab platform.
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Design, synthesis, and anticancer properties of Isocorydine derivatives.
Bioorganic & Medicinal Chemistry, 2017Co-Authors: Qian Yan, Junxi Liu, Aiyi Xin, Yin Han, Yanxia Zhang, Di DuolongAbstract:Abstract Isocorydine (ICD), an aporphine alkaloid, is widely distributed in nature. Its ability to target side population (SP) cells found in human hepatocellular carcinoma (HCC) makes it and its derivative 8-amino-Isocorydine (NICD) promising chemotherapeutic agents for the treatment of HCC. To improve the anticancer activity of Isocorydine derivatives, twenty derivatives of NICD were designed and synthesized through chemical structure modifications of the aromatic amino group at C-8. The anti-proliferative activities of all synthesized compounds against human hepatocellular (HepG2), cervical (HeLa), and gastric (MGC-803) cancer cell lines were evaluated using an MTT assay. The results showed that all the synthetic compounds had some tumor cell growth inhibitory activity. The compound COM33 ( 24 ) was the most active with IC 50 values under 10 μM (IC 50 for HepG2 = 7.51 µM; IC 50 for HeLa = 6.32 μM). FICD ( 12 ) and COM33 ( 24 ) were selected for further investigation of their in vitro and in vivo activities due to their relatively good antiproliferative properties. These two compounds significantly downregulated the expression of four key proteins (C-Myc, β-Catenin, CylinD1, and Ki67) in HepG2 cells. The tumor inhibition rate of COM33 ( 24 ) in vivo was 73.8% after a dose 100 mg/kg via intraperitoneal injection and the combined inhibition rate of COM33 ( 24 ) (50 mg/kg) with sorafenib (50 mg/kg) was 66.5%. The results indicated that these Isocorydine derivatives could potentially be used as targeted chemotherapy agents or could be further developed in combination with conventional chemotherapy drugs to target cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT), the main therapeutic targets in HCC.
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Research on anticancer activity of Isocorydine and its derivatives
China journal of Chinese materia medica, 2017Co-Authors: Qian Yan, Aiyi Xin, Junxi LiuAbstract:Isocorydine and its analogs were extracted from Dicranostigma leptopodum and Stephania yunnanensis through the method of natural products chemistry. Its derivatives were prepared by chemical structure modifications from Isocorydine. MTT method was used to study the inhibitory effect of those compounds on the growth of HepG2, HeLa and MGC-803 cancer cell lines in vitro. The results showed that Isocorydine and its analogs all have the growth inhibition for those cancer cell lines. This paper investigated the structure-activity relationship of Isocorydine and its derivatives with anticancer activity in the aspect of stereochemical structure, functional groups positions of the compounds and the electron density of aromatic rings based on the single crystal diffraction structure and the molecular docking of EGFR and Isocorydine.
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derivate Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing g2 m cell cycle arrest and apoptosis
Tumor Biology, 2016Co-Authors: Lijuan Chen, Junxi Liu, Lixing Zhang, Fangyu Zhao, Tingpu Wang, Hua Tian, Ming YaoAbstract:We have previously demonstrated that Isocorydine (ICD) can be served as a potential antitumor agent in hepatocellular carcinoma (HCC). A novel derivate of Isocorydine (d-ICD) could significantly improve its anticancer activity in tumors. However, the molecular mechanisms of d-ICD on HCC cells remain to be unclear. In this study, we observed that d-ICD inhibited cell proliferation and induced apoptosis of HCC cells in a concentration-dependent manner. We found d-ICD induced G2/M cycle arrest of HCC cells via DNA damage 45 alpha (GADD45A) and p21 pathway in vitro and in vivo. In d-ICD-treated cells, cell cycle-related proteins cyclin B1 and p-CDC2 were upregulated and p-cyclin B1, CDC2, and E2F1 were inhibited. p21 expression can be reversed by knockdown of GADD45A in d-ICD-treated HCC cells. Enforced expression of CCAAT/enhancer-binding protein β (C/EBPβ) in combination with d-ICD enhanced the p21 expression in HCC cells. Furthermore, the luciferase reporter assay showed that upregulation of GADD45A by C/EBPβ was achieved through the increase of GADD45A promoter activity. These findings indicate that d-ICD inhibits cell proliferation and induces cell cycle arrest through activation of C/EBPβ-GADD45A-p21 pathway in HCC cells. d-ICD might be a promising chemotherapeutic agent for the treatment of HCC.
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Total content determination for the effective fraction of the alkaloids in Dicranostigma leptopodum (Maxim.) Fedde by HPLC and ultraviolet-visible spectrophotometry
Analytical Methods, 2016Co-Authors: Yali Chen, Mei Zhong, Junxi Liu, Qian Yan, Rongrong Gao, Quanyi ZhaoAbstract:For the quality control and the rational use of the effective fraction of the alkaloids (EFA) in Dicranostigma leptopodum (Maxim.) Fedde (DLF), extraction and determination methods for EFA were developed in the present study. The purification of EFA was carried out on the D101 macroporous resin. The high-performance liquid chromatography with the diode-array detection (HPLC-DAD) method was established to determine the total alkaloid content of EFA. In this method, 0.4% ionic liquid (1-butyl-3-methylimidazole tetrafluoroborate) was added into the mobile phase as the tailing-suppression reagent. 5-hydroxy-coptisine, isocorytuberine, protopine, allocryptopine, coptisine, berberine, corydine, and Isocorydine were selected as reference standards for the determination, and the total alkaloid content was calculated as their sum in EFA. The results suggested that the total alkaloid content of EFA was 19.04 ± 1.23% (n = 3). Since corresponding reference standards for the alkaloids of DLF are lacking, ultraviolet-visible (UV-Vis) spectrophotometry was also developed for the determination of the total alkaloid content of EFA. In this method, Isocorydine was selected as the reference compound for the determination of the total alkaloid content and the results suggested that the total alkaloid content of EFA was 65.92 ± 1.33% (n = 3). These newly established methods were rapid and accurate with high repeatability, and can be applied for the further use of EFA in DLF.
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Derivate Isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/M cell cycle arrest and apoptosis.
Tumor Biology, 2015Co-Authors: Lijuan Chen, Junxi Liu, Lixing Zhang, Fangyu Zhao, Tingpu Wang, Hua Tian, Ming YaoAbstract:We have previously demonstrated that Isocorydine (ICD) can be served as a potential antitumor agent in hepatocellular carcinoma (HCC). A novel derivate of Isocorydine (d-ICD) could significantly improve its anticancer activity in tumors. However, the molecular mechanisms of d-ICD on HCC cells remain to be unclear. In this study, we observed that d-ICD inhibited cell proliferation and induced apoptosis of HCC cells in a concentration-dependent manner. We found d-ICD induced G2/M cycle arrest of HCC cells via DNA damage 45 alpha (GADD45A) and p21 pathway in vitro and in vivo. In d-ICD-treated cells, cell cycle-related proteins cyclin B1 and p-CDC2 were upregulated and p-cyclin B1, CDC2, and E2F1 were inhibited. p21 expression can be reversed by knockdown of GADD45A in d-ICD-treated HCC cells. Enforced expression of CCAAT/enhancer-binding protein β (C/EBPβ) in combination with d-ICD enhanced the p21 expression in HCC cells. Furthermore, the luciferase reporter assay showed that upregulation of GADD45A by C/EBPβ was achieved through the increase of GADD45A promoter activity. These findings indicate that d-ICD inhibits cell proliferation and induces cell cycle arrest through activation of C/EBPβ-GADD45A-p21 pathway in HCC cells. d-ICD might be a promising chemotherapeutic agent for the treatment of HCC.
Bakyta Matej - One of the best experts on this subject based on the ideXlab platform.
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Biological activity of plants metabolites. XIX. Alkaloids of Peumus boldus MOL.
2012Co-Authors: Bakyta MatejAbstract:Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Matej Bakyta Consultant: Doc. RNDr. Lubomír Opletal, CSc. Title of Diploma Thesis: Biological activity of plants metabolites. XIX. Alkaloids of Peumus boldus MOL. A chloroform extract (pH 9-10, tertiary alkaloidal bases) was prepared from the leaves of Peumus boldus Mol. Processing of this extract by column chromatography and subsequent crystallization of fractions 34-39 led to the isolation of a compound named MB-1. The compound was identified as an aporphine alkaloid (+)-Isocorydine (m. t. 183-184 řC) on the basis of results of spectral analysis (MS and NMR studies) and their comparison with literature. The isolated compound was tested for human blood acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BuChE) inhibition activity and for antioxidative activity (DPPH test). (+)-Isocorydine did not show significant human cholinesterase inhibition activity (AChE: IC50 >1000 μM; BuChE: IC50 = 657,1 μM) in comparison with reference compounds and did not show significant antioxidative effect in DPPH test (EC50 >1000 μM) in comparison with reference antioxidants. Key words: Peumus boldus, (+)-Isocorydine, acetylcholinesterase, butyrylcholinesterase, antioxidative..
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Biological activity of plants metabolites. XIX. Alkaloids of Peumus boldus MOL.
Univerzita Karlova Farmaceutická fakulta v Hradci Králové, 2012Co-Authors: Bakyta MatejAbstract:Univerzita Karlova v Praze Farmaceutická fakulta v Hradci Králové Katedra farmaceutické botaniky a ekologie Kandidát: Matej Bakyta Konzultant: Doc. RNDr. Lubomír Opletal, CSc. Názov diplomovej práce: Biologická aktivita obsahových látek rostlin XIX. Alkaloidy Peumus boldus MOL. Z listov Peumus boldus Mol. bol pripravený chloroformový extrakt (pH 9-10, terciárne alkaloidné bázy). Spracovanie extraktu stĺpcovou chromatografiou a následná kryštalizácia spojených frakcií 34-39 viedli k izolácii látky označené MB-1, ktorá bola na základe výsledkov spektrální analýzy (MS a NMR štúdií) a porovnania výsledkov s literatúrou identifikovaná ako aporfínový alkaloid (+)-izokorydín (t. t. 183-184 řC). Izolovaný alkaloid bol testovaný na inhibičnú aktivitu voči ľudskej erytrocytárnej acetylcholínesteráze (AChE) a plazmatickej butyrylcholínesteráze (BuChE) a na antioxidačnú aktivitu (DPPH test). (+)-Izokrydín neprejavil v porovnaní s referenčnými látkami významnú inhibičnú aktivitu voči ľudským cholínesterázam (AChE: IC50 >1000 μM; BuChE: IC50 = 657,1 μM) a v porovaní s referenčnými antioxidantami neprejavil významný antioxidačný účinok (EC50 >1000 μM). Kľúčové slová: Peumus boldus, (+)-izokorydín, acetylcholínesteráza, butyrylcholínesteráza, antioxidačná aktivitaCharles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Matej Bakyta Consultant: Doc. RNDr. Lubomír Opletal, CSc. Title of Diploma Thesis: Biological activity of plants metabolites. XIX. Alkaloids of Peumus boldus MOL. A chloroform extract (pH 9-10, tertiary alkaloidal bases) was prepared from the leaves of Peumus boldus Mol. Processing of this extract by column chromatography and subsequent crystallization of fractions 34-39 led to the isolation of a compound named MB-1. The compound was identified as an aporphine alkaloid (+)-Isocorydine (m. t. 183-184 řC) on the basis of results of spectral analysis (MS and NMR studies) and their comparison with literature. The isolated compound was tested for human blood acetylcholinesterase (AChE) and human plasma butyrylcholinesterase (BuChE) inhibition activity and for antioxidative activity (DPPH test). (+)-Isocorydine did not show significant human cholinesterase inhibition activity (AChE: IC50 >1000 μM; BuChE: IC50 = 657,1 μM) in comparison with reference compounds and did not show significant antioxidative effect in DPPH test (EC50 >1000 μM) in comparison with reference antioxidants. Key words: Peumus boldus, (+)-Isocorydine, acetylcholinesterase, butyrylcholinesterase, antioxidative...Department of Pharmaceutical Botany and EcologyKatedra farmaceutické botaniky a ekologieFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov
R. Shakirov - One of the best experts on this subject based on the ideXlab platform.
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Berberis alkaloids. XXXIV. Turcomanine — a new alkaloid from Berberis turcomanica
Chemistry of Natural Compounds, 2013Co-Authors: I. Khamidov, M. Faskhutdinov, M. V. Telezhenetskaya, M. G. Levkovich, Akmal Karimov, N. D. Abdullaev, R. ShakirovAbstract:Berberine, Isocorydine, glaucine, thalicmidine, aromoline, oxyacanthine, and the new 1-benzylisoquinoline alkaloid turcomanine have been isolated fromBerberis turcomanica Kar. The structure of the new alkaloid has been established on the basis of chemical transformations and spectral characteristics. This is the first time that Isocorydine, thalicmidine, aromoline, and oxyacanthine have been isolated from this plant.
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Berberis alkaloids. XXXIV. Turcomanine — a new alkaloid fromBerberis turcomanica
Chemistry of Natural Compounds, 1996Co-Authors: I. Khamidov, M. Faskhutdinov, M. V. Telezhenetskaya, M. G. Levkovich, Akmal Karimov, N. D. Abdullaev, R. ShakirovAbstract:Berberine, Isocorydine, glaucine, thalicmidine, aromoline, oxyacanthine, and the new 1-benzylisoquinoline alkaloid turcomanine have been isolated from Berberis turcomanica Kar. The structure of the new alkaloid has been established on the basis of chemical transformations and spectral characteristics. This is the first time that Isocorydine, thalicmidine, aromoline, and oxyacanthine have been isolated from this plant.
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Berberis alkaloids XXXII. Berberal — A new alkaloid fromBerberis heterobotrys
Chemistry of Natural Compounds, 1993Co-Authors: Akmal Karimov, M. Faskhutdinov, M. G. Levkovich, N. D. Abdullaev, E. G. Mil'grom, Ya V. Rashkes, R. ShakirovAbstract:Berberine, palmatine, jatrorrhizine, oxyacanthine, berbamine, reticuline, obaberine, Isocorydine, thalicmidine, and the new base berberal (I) have been isolated from leaves and young shoots of Berberis heterobotrys Wolf. The structure of berberal has been established by a study of its^1H and^13C NMR spectra and measurement of intramolecular NOEs, and also by mass-spectrometric analysis.
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Berberis alkaloids. XXII. Interbrinine and intebrimine — New alkaloids from Berberis integerrima
Chemistry of Natural Compounds, 1993Co-Authors: Akmal Karimov, V. I. Vinogradova, R. ShakirovAbstract:The known alkaloids reticuline, isoboldine, Isocorydine, glaucine, armepavine, oxyacanthine, and heliamine and the new alkaloids intebrinine and intebrimine have been isolated from the total alkaloids of the leaves of Berberis integerrima , and structures have been proposed for the latter two on the basis of spectral characteristics and independent synthesis.
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Berberis alkaloids. XVII. Investigation of the alkaloids of Berberis heteropoda
Chemistry of Natural Compounds, 1993Co-Authors: M. M. Yusupov, M. G. Levkovich, Akmal Karimov, N. D. Abdullaev, R. ShakirovAbstract:The alkaloid composition of young shoots and leaves of Berberis heteropoda Schrenk has been studied. In addition to known alkaloids, two new ones have been isolated — N-methyldihydroberberine and 8-oxoberberrubine, the structures of which were established by chemical transformations and a study of spectral properties. Of known alkaloids, berbamunine, aromoline, glaucine, thalicmidine, Isocorydine, and reticuline have been found in this plant for the first time. Pseudopalmitine and laudanosine have been found for the first time in plants of the genus Berberis .
Khalijah Awang - One of the best experts on this subject based on the ideXlab platform.
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Ultraviolet-visible study on acid-base equilibria of aporphine alkaloids with antiplasmodial and antioxidant activities from Alseodaphne corneri and Dehaasia longipedicellata
Scientific Reports, 2016Co-Authors: Azeana Zahari, Mohammad Niyaz Khan, Abdulwali Ablat, Noridayu Omer, Mohd Azlan Nafiah, Yasodha Sivasothy, Jamaludin Mohamad, Khalijah AwangAbstract:The UV-vis spectra of Isocorydine 1 , norIsocorydine 2 and boldine 3 were studied in 2% v/v acetonitrile, at constant ionic strength (0.1 M NaCl, 35 degree Celsius). The p K _ a values of Isocorydine 1 and norIsocorydine 2 were 11.75 and 12.07, respectively. Boldine 3 gave a p K _ a value of 9.16 and 10.44. All of the alkaloids 1 – 3 were stable at physiological pH; thereby all of them will not ionize, thus permitting the basic nitrogen to be protonated and accumulated within the acidic food vacuole of Plasmodium via pH trapping. Subsequently, acidic food vacuoles that have been neutralized by alkaloids would result in enhancement of the antiplasmodial activity. The alkaloids showed antiplasmodial activity against Plasmodium falciparum and antioxidant activities; DPPH radical scavenging, metal chelating and ferric reducing power. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids can also prevent oxidative damage. It can be prevented by binding free heme and neutralizing the electrons produced during the Plasmodium falciparum mediated haemoglobin destruction in the host. Slightly basic properties of the aforementioned alkaloids, along with their antioxidant activities, are advantageous in improving the suppression of malaria infection that cause less damage to the host.
Qian Yan - One of the best experts on this subject based on the ideXlab platform.
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Design, synthesis, and anticancer properties of Isocorydine derivatives.
Bioorganic & Medicinal Chemistry, 2017Co-Authors: Qian Yan, Junxi Liu, Aiyi Xin, Yin Han, Yanxia Zhang, Di DuolongAbstract:Abstract Isocorydine (ICD), an aporphine alkaloid, is widely distributed in nature. Its ability to target side population (SP) cells found in human hepatocellular carcinoma (HCC) makes it and its derivative 8-amino-Isocorydine (NICD) promising chemotherapeutic agents for the treatment of HCC. To improve the anticancer activity of Isocorydine derivatives, twenty derivatives of NICD were designed and synthesized through chemical structure modifications of the aromatic amino group at C-8. The anti-proliferative activities of all synthesized compounds against human hepatocellular (HepG2), cervical (HeLa), and gastric (MGC-803) cancer cell lines were evaluated using an MTT assay. The results showed that all the synthetic compounds had some tumor cell growth inhibitory activity. The compound COM33 ( 24 ) was the most active with IC 50 values under 10 μM (IC 50 for HepG2 = 7.51 µM; IC 50 for HeLa = 6.32 μM). FICD ( 12 ) and COM33 ( 24 ) were selected for further investigation of their in vitro and in vivo activities due to their relatively good antiproliferative properties. These two compounds significantly downregulated the expression of four key proteins (C-Myc, β-Catenin, CylinD1, and Ki67) in HepG2 cells. The tumor inhibition rate of COM33 ( 24 ) in vivo was 73.8% after a dose 100 mg/kg via intraperitoneal injection and the combined inhibition rate of COM33 ( 24 ) (50 mg/kg) with sorafenib (50 mg/kg) was 66.5%. The results indicated that these Isocorydine derivatives could potentially be used as targeted chemotherapy agents or could be further developed in combination with conventional chemotherapy drugs to target cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT), the main therapeutic targets in HCC.
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Research on anticancer activity of Isocorydine and its derivatives
China journal of Chinese materia medica, 2017Co-Authors: Qian Yan, Aiyi Xin, Junxi LiuAbstract:Isocorydine and its analogs were extracted from Dicranostigma leptopodum and Stephania yunnanensis through the method of natural products chemistry. Its derivatives were prepared by chemical structure modifications from Isocorydine. MTT method was used to study the inhibitory effect of those compounds on the growth of HepG2, HeLa and MGC-803 cancer cell lines in vitro. The results showed that Isocorydine and its analogs all have the growth inhibition for those cancer cell lines. This paper investigated the structure-activity relationship of Isocorydine and its derivatives with anticancer activity in the aspect of stereochemical structure, functional groups positions of the compounds and the electron density of aromatic rings based on the single crystal diffraction structure and the molecular docking of EGFR and Isocorydine.
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Total content determination for the effective fraction of the alkaloids in Dicranostigma leptopodum (Maxim.) Fedde by HPLC and ultraviolet-visible spectrophotometry
Analytical Methods, 2016Co-Authors: Yali Chen, Mei Zhong, Junxi Liu, Qian Yan, Rongrong Gao, Quanyi ZhaoAbstract:For the quality control and the rational use of the effective fraction of the alkaloids (EFA) in Dicranostigma leptopodum (Maxim.) Fedde (DLF), extraction and determination methods for EFA were developed in the present study. The purification of EFA was carried out on the D101 macroporous resin. The high-performance liquid chromatography with the diode-array detection (HPLC-DAD) method was established to determine the total alkaloid content of EFA. In this method, 0.4% ionic liquid (1-butyl-3-methylimidazole tetrafluoroborate) was added into the mobile phase as the tailing-suppression reagent. 5-hydroxy-coptisine, isocorytuberine, protopine, allocryptopine, coptisine, berberine, corydine, and Isocorydine were selected as reference standards for the determination, and the total alkaloid content was calculated as their sum in EFA. The results suggested that the total alkaloid content of EFA was 19.04 ± 1.23% (n = 3). Since corresponding reference standards for the alkaloids of DLF are lacking, ultraviolet-visible (UV-Vis) spectrophotometry was also developed for the determination of the total alkaloid content of EFA. In this method, Isocorydine was selected as the reference compound for the determination of the total alkaloid content and the results suggested that the total alkaloid content of EFA was 65.92 ± 1.33% (n = 3). These newly established methods were rapid and accurate with high repeatability, and can be applied for the further use of EFA in DLF.
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Asymmetric total synthesis of (S)-Isocorydine
Tetrahedron-asymmetry, 2015Co-Authors: Mei Zhong, Junxi Liu, Yali Chen, Qian Yan, Yun-bin Jiang, Di DuolongAbstract:Abstract The asymmetric total synthesis of ( S )-Isocorydine, a potential drug for the cure of hepatocellular carcinoma, is described. Asymmetric transfer hydrogenation of 3,4-dihydroisoquinoline using a chiral Ru(II) catalyst was applied to the synthesis of Isocorydine as the key step, in which the ee value achieved is up to 99%. The overall yield is 9.4% after 12 synthetic procedures.
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Study on pharmacokinetics and tissue distribution of the Isocorydine derivative (AICD) in rats by HPLC-DAD method.
Acta Pharmaceutica Sinica B, 2015Co-Authors: Yali Chen, Mei Zhong, Junxi Liu, Qian Yan, Quanyi Zhao, Di Duolong, Jinxia LiuAbstract:A simple and effective high-performance liquid chromatography with diode-array detection method coupled with a liquid-liquid extraction pretreatment has been developed for determining the pharmacokinetics and tissue distribution of a novel structurally modified derivative (8-acetamino-Isocorydine) of Isocorydine. According to the in vivo experiments data calculations by DAS 2.0 software, a two-compartment metabolic model was suitable for describing the pharmacokinetic of 8-acetamino-Isocorydine in rats. 8-Acetamino-Isocorydine was absorbed well after oral administration, and the absolute bioavailability was 76.5%. The half-life of 8-acetamino-Isocorydine after intravenous and oral administration was 2.2 h and 2.0 h, respectively. In vivo, 8-acetamino-Isocorydine was highly distributed in the lungs, kidney and liver; however, relatively little entered the brain, suggesting that 8-acetamino-Isocorydine could not easily pass through the blood brain barrier. Our work describes the first characterization of the pharmacokinetic parameters and tissue distribution of 8-acetamino-Isocorydine. The acquired data will provide useful information for the in vivo pharmacology of 8-acetamino-Isocorydine, and can be applied to new drug research.
