Accendatech Company

Tianjin, China

Accendatech Company

Tianjin, China
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An Y.,Chinese PLA General Hospital | Guo W.,Beijing Institute of Radiation Medicine | Li L.,Beijing Institute of Radiation Medicine | Xu C.,Beijing Institute of Radiation Medicine | And 6 more authors.
PLoS ONE | Year: 2015

Background: There is no highly effective chemotherapy for malignant gliomas to date.We found that dimethylaminomicheliolide (DMAMCL), a selective inhibitor of acute myeloid leukemia (AML) stem/progenitor cells, inhibited the growth of glioma cells. Methods: The distribution of DMAMCL in brain was analyzed by an ultraperformance liquid chromatography- mass spectrometry (UPLC-MS/MS) system. The anti-tumor evaluations of DMAMCL in vitro were performed by MTT, FACS and RT-PCR. In vivo, the mixture of C6 cells and matrigel was injected into caudatum, and the anti-tumor activity of DMAMCL was evaluated by tumor growth and rat survival. The toxicity of DMAMCL was evaluated by body weight, daily food intake, hematological or serum biochemical analyses, and histological appearance of tissues. Results: The IC50 values of DMAMCL against the C6 and U-87MG cell lines in vitro were 27.18 ± 1.89 μM and 20.58 ± 1.61 μM, respectively. DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dosedependent manner. In a C6 rat tumor model, daily administration of DMAMCL for 21 days reduced the burden of C6 tumors by 60% to 88% compared to controls, and more than doubled the mean lifespan of tumor-bearing rats. Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma. Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity. Conclusions: These results suggest that DMAMCL is highly promising for the treatment of glioma. © 2015 An et al.


PubMed | Nankai University, Chinese PLA General Hospital, Accendatech Co. and Beijing Institute of Radiation Medicine
Type: Journal Article | Journal: PloS one | Year: 2015

There is no highly effective chemotherapy for malignant gliomas to date. We found that dimethylaminomicheliolide (DMAMCL), a selective inhibitor of acute myeloid leukemia (AML) stem/progenitor cells, inhibited the growth of glioma cells.The distribution of DMAMCL in brain was analyzed by an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) system. The anti-tumor evaluations of DMAMCL in vitro were performed by MTT, FACS and RT-PCR. In vivo, the mixture of C6 cells and matrigel was injected into caudatum, and the anti-tumor activity of DMAMCL was evaluated by tumor growth and rat survival. The toxicity of DMAMCL was evaluated by body weight, daily food intake, hematological or serum biochemical analyses, and histological appearance of tissues.The IC50 values of DMAMCL against the C6 and U-87MG cell lines in vitro were 27.18 1.89 M and 20.58 1.61 M, respectively. DAMMCL down-regulated the anti-apoptosis gene Bcl-2 and increased apoptosis in C6 and U-87MG cells in a dose-dependent manner. In a C6 rat tumor model, daily administration of DMAMCL for 21 days reduced the burden of C6 tumors by 60% to 88% compared to controls, and more than doubled the mean lifespan of tumor-bearing rats. Distribution analysis showed that the DMAMCL concentration was higher in the brain than in plasma. Evaluations for toxicity revealed that oral administration of DMAMCL at 200 or 300 mg/kg once a day for 21 days did not result in toxicity.These results suggest that DMAMCL is highly promising for the treatment of glioma.


Long J.,Nankai University | Ding Y.-H.,Accendatech Co. | Wang P.-P.,Nankai University | Zhang Q.,Nankai University | Chen Y.,Nankai University
Journal of Organic Chemistry | Year: 2013

Parthenolide showed extensive bioactivities including selective eradication of AML stem cells. Herein we report protection-free semisyntheses of parthenolide and its cyclopropyl analogue (compound 10) from the abundant natural product costunolide with an overall yield of 55 and 60%, respectively. Compound 10 was more stable than parthenolide, and it maintained comparable activities against AML cell lines and AML stem cells. Therefore, compound 10 might be a superior small molecule than parthenolide as a tool for investigation of cancer stem cell biology. © 2013 American Chemical Society.


Yang Z.-J.,Nankai University | Ge W.-Z.,Nankai University | Li Q.-Y.,Nankai University | Lu Y.,Nankai University | And 8 more authors.
Journal of Medicinal Chemistry | Year: 2015

Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between β,-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular α-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoromethylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes. © 2015 American Chemical Society.


Zhai J.-D.,Nankai University | Li D.,Nankai University | Long J.,Nankai University | Zhang H.-L.,Nankai University | And 4 more authors.
Journal of Organic Chemistry | Year: 2012

The semisynthesis of arglabin, an anticancer drug in clinical application, is developed from abundant natural product parthenolide via three steps. Each step in this sequence is highly stereoselective, and the substrate-dependent stereoselectivity in the epoxidation step can be explained by computational calculations. The success of chemical semisynthesis of arglabin suggests that the biosynthesis of arglabin might proceed in a similar pathway. © 2012 American Chemical Society.


Ma W.-W.,Nankai University | Shi Q.-Q.,Tianjin University of Science and Technology | Ding Y.-H.,Accendatech Co. | Long J.,Nankai University | And 2 more authors.
Molecules | Year: 2013

Micheliolide (MCL) derivatives with etherification or esterification of the hydroxyl group at the C4 position were synthesized and evaluated for their activities against different acute myelogenous leukemia (AML) cell lines. These derivatives demonstrated comparable activities against AML cell lines HL-60 and doxorubicin resistant cell line HL-60/A. As to multi-drug resistant AML progenitor cells KG-1a, MCL and some of its derivatives maintained significant activities, and only 1.1-2.7 fold activity reductions were observed when compared with the activities against HL-60, while doxorubicin showed 20-fold activity reduction. Our study demonstrated that the C4 hydroxyl group of MCL might not only be a suitable position for structural modifications, but also be a starting point for the design of appropriate molecular probes to explore the specific targets in the progenitor cell line KG-1a. © 1996-2013 MDPI AG (Basel, Switzerland).


Yang X.-D.,Nankai University | Dong C.-M.,Nankai University | Chen J.,Nankai University | Ding Y.-H.,Accendatech Company | And 4 more authors.
Chemistry - An Asian Journal | Year: 2013

The Tup fragments of tubulysins were synthesized with a tandem reaction as the key step, and unexpected diastereoselectivity was observed in the first Grignard addition stage. The coupling of the enolate of a thiazolyl ketone with chiral sulfinimines furnished the backbone of the Tuv fragment with over 100:1 d.r. and high yield. Thus, tubulysin U and C-4 ep-tubulysin U were prepared in a highly selective and efficient manner. The results of the MTT assay furthermore indicated that C-4 ep-tubulysin U maintained significant growth inhibition activities against several cancer cell lines. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Zhang Q.,Nankai University | Lu Y.,Nankai University | Ding Y.,Nankai University | Zhai J.,Nankai University | And 21 more authors.
Journal of Medicinal Chemistry | Year: 2012

Small molecules that can selectively target cancer stem cells (CSCs) remain rare currently and exhibit no common structural features. Here we report a series of guaianolide sesquiterpene lactones (GSLs) and their derivatives that can selectively eradicate acute myelogenous leukemia (AML) stem or progenitor cells. Natural GSL compounds arglabin, an anticancer clinical drug, and micheliolide (MCL), are able to reduce the proportion of AML stem cells (CD34+CD38-) in primary AML cells. Targeting of AML stem cells is further confirmed by a sharp reduction of colony-forming units of primary AML cells upon MCL treatment. Moreover, DMAMCL, the dimethylamino Michael adduct of MCL, slowly releases MCL in plasma and in vivo and demonstrates remarkable therapeutic efficacy in the nonobese diabetic/severe combined immunodeficiency AML models. These findings indicate that GSL is an ample source for chemical agents against AML stem or progenitor cells and that GSL is potentially highly useful to explore anti-CSC approaches. © 2012 American Chemical Society.


Trademark
ACCENDATECH Co. | Date: 2016-11-07

Chemical contraceptives; Drug testing kits comprised of medical diagnostic reagents and assays that test for the presence of alcohol, drugs; Medicinal preparations for the mouth to be applied in the form of drops, capsules, tablets and compressed tablets; Plant extracts for pharmaceutical purposes; Anti-epileptic pharmaceutical preparations; Antibiotic tablets; Donkey-hide gelatin (Ejiao) for Chinese medicinal use; Dried Chinese boxthorn fruits for Chinese medicinal use; Medicinal preparations for the mouth to be applied in the form of drops, capsules, tablets and compressed tablets; Prescription and non-prescription medicines, namely, pills, tablets, capsules, caplets, liquid drops, sachets and pharmaceutical preparations for the treatment of cardiovascular disorders; Prescription and non-prescription medicines, namely, pills, tablets, capsules, caplets, liquid drops, sachets and pharmaceutical preparations for the treatment of cardiovascular disorders; Transdermal patches featuring smoking cessation preparations, caffeine for use as a stimulant, vitamins for increasing energy; Vitamin tablets; Wheat-free and gluten-free pasta, crackers for the treatment of special medical and health conditions.


PubMed | Nankai University and Accendatech Company
Type: Journal Article | Journal: Journal of medicinal chemistry | Year: 2015

Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between ,-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular -alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoromethylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes.

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