scholarly journals ‘Click Chemistry’ Synthesis of Novel Natural Product-Like Caged Xanthones Bearing a 1,2,3-Triazole Moiety with Improved Druglike Properties as Orally Active Antitumor Agents

Molecules ◽  
2017 ◽  
Vol 22 (11) ◽  
pp. 1834 ◽  
Author(s):  
Xiang Li ◽  
Yue Wu ◽  
Yanyan Wang ◽  
Qidong You ◽  
Xiaojin Zhang
Keyword(s):  
Click Chemistry ◽  
Natural Product ◽  
Antitumor Agents ◽  
Orally Active

scholarly journals Design, Synthesis, and Biological Activity of Sulfonamide Analogues of Antofine and Cryptopleurine as Potent and Orally Active Antitumor Agents

2015 ◽  
Vol 58 (19) ◽  
pp. 7749-7762 ◽  
Author(s):  
Yongseok Kwon ◽  
Jayoung Song ◽  
Honggu Lee ◽  
Eun-Yeong Kim ◽  
Kiho Lee ◽  
...  
Keyword(s):  
Biological Activity ◽  
Antitumor Agents ◽  
Design Synthesis ◽  
Orally Active

In cell scalaradial interactome profiling using a bio-orthogonal clickable probe

2014 ◽  
Vol 50 (45) ◽  
pp. 6043-6045 ◽  
Author(s):  
C. Cassiano ◽  
L. Margarucci ◽  
R. Esposito ◽  
R. Riccio ◽  
A. Tosco ◽  
...  
Keyword(s):  
Click Chemistry ◽  
Natural Product ◽  
Marine Natural Product ◽  
Anti Inflammatory

A bio-orthogonal click-chemistry procedure was developed to allow thein cellinteractome profiling of scalaradial, an anti-inflammatory marine natural product.

1-Methylisoguanosine: An orally active marine natural product with skeletal muscle and cardiovascular effects

Life Sciences ◽  
1980 ◽  
Vol 26 (13) ◽  
pp. 1069-1077 ◽  
Author(s):  
J. Baird-Lambert ◽  
J.F. Marwood ◽  
L.P. Davies ◽  
K.M. Taylor
Keyword(s):  
Skeletal Muscle ◽  
Natural Product ◽  
Cardiovascular Effects ◽  
Marine Natural Product ◽  
Orally Active

scholarly journals Correction: CuAAC click chemistry for the enhanced detection of novel alkyne-based natural product toxins

2018 ◽  
Vol 54 (93) ◽  
pp. 13161-13161
Author(s):  
Edward S. Hems ◽  
Ben A. Wagstaff ◽  
Gerhard Saalbach ◽  
Robert A. Field
Keyword(s):  
Click Chemistry ◽  
Natural Product

Correction for 'CuAAC click chemistry for the enhanced detection of novel alkyne-based natural product toxins' by Edward S. Hems et al., Chem. Commun., 2018, 54, 12234–12237.

A novel, selective, orally active, potent small molecule inhibitor of Hsp90

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13067-13067 ◽  
Author(s):  
P. M. Steed ◽  
P. Fadden ◽  
S. Hall
Keyword(s):  
Body Weight ◽  
Natural Product ◽  
Small Molecule ◽  
Clinical Chemistry ◽  
Water Soluble ◽  
Tumor Growth Inhibition ◽  
Hsp90 Inhibition ◽  
Multiple Dosing ◽  
Oral Doses ◽  
Orally Active

13067 Background: The preclinical and clinical data evaluating derivatives of the natural product geldanamycin, including 17-AAG and 17-DMAG, reveal that inhibition of the molecular chaperone HSP90 results in multiple anti-tumor effects. SNX-5422 and SNX-5542 are potent, novel, highly specific, water soluble and orally active small molecule inhibitors of Hsp90. Here we describe the preclinical efficacy and toxicity evaluation of these compounds. Methods: The PK profile of SNX-5422 and SNX-5542 was determined following oral and iv dosing in mice and rats. HT29 xenografts were performed oral doses of SNX-5542 on a schedule of Q2DX3,2 for 2 weeks or 17-DMAG on the previously reported regimen of bid×5,2 for 2 weeks, with tumor progression and body weight monitored. Plasma, tumor and other tissues were harvested for evaluation of HSP70 induction and levels of HSP90 client proteins. Rats were treated with varying oral doses on a schedule of Q2DX3,2 for two weeks. Clinical observations were noted and standard hematology and clinical chemistry parameters were monitored. Results: SNX-5542 exhibited 37% oral BA in rats and >75% in mice, with t½ >7h in each species. SNX-5542 was well tolerated in normal and tumor-bearing mice at 300 mg/m2 Q2DX3,2 for 2 weeks, 0.9% weight gain. 17-DMAG at 30 mg/m2 bid×5,2 for 2 weeks caused 3.3% body weight loss. At these doses, SNX-5542 exhibited 78% median tumor growth inhibition of HT29 tumors while 17-DMAG exhibited 23% inhibition. Mechanistic indicators of HSP90 inhibition correlated with efficacy across multiple dosing levels. At 120 mg/m2 Q2DX3,2 for 2 weeks SNX-5422 was well tolerated in rats, with no significant effect on any clinical, hematology or clinical chemistry parameter with the exception of a slight increase in blood urea nitrogen levels. Histopathological evaluation of liver, thymus, spleen and kidneys revealed no significant treatment-related effects. At 120 mg/m2 Q2DX3,2 for 13 days SNX-5422 does not exhibit any of the toxicities reported for 17-DMAG (bidX5,2 for 8 days at 24 mg/m2). Conclusions: SNX small-molecule HSP90 inhibitors have favorable pharmacokinetic profiles, oral bioavailability, tolerability and superior anti-tumor activity compared to the natural product derivative 17-DMAG. [Table: see text]

scholarly journals CuAAC click chemistry for the enhanced detection of novel alkyne-based natural product toxins

2018 ◽  
Vol 54 (86) ◽  
pp. 12234-12237 ◽  
Author(s):  
Edward S. Hems ◽  
Ben A. Wagstaff ◽  
Gerhard Saalbach ◽  
Robert A. Field
Keyword(s):  
Natural Products ◽  
Click Chemistry ◽  
Natural Product ◽  
Harmful Algal Blooms ◽  
Algal Blooms ◽  
Terminal Alkyne

In the context of discovering and quantifying terminal alkyne-based natural products, here we report the combination of CuAAC click chemistry with LC-MS for the detection of polyether toxins (prymnesins) associated with harmful algal blooms.

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