scholarly journals Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

2013 ◽  
Vol 9 ◽  
pp. 2328-2335 ◽  
Author(s):  
Johann Moschner ◽  
Anna Chentsova ◽  
Nicole Eilert ◽  
Irene Rovardi ◽  
Philipp Heretsch ◽  
...  
Keyword(s):  
Nitrogen Atom ◽  
Hedgehog Signaling ◽  
Potent Inhibitor ◽  
Biological Evaluation ◽  
Luciferase Expression ◽  
Acid Stability ◽  
Methyl Group ◽  
F Ring ◽  
Synthesis And Biological Evaluation ◽  
Acid Stable

The chemical synthesis and biological evaluation of new cyclopamine analogs bearing exocyclic methylenes in different positions is described. Bis-exo-cyclopamine 6 was identified as a potent inhibitor of the Gli1-dependent luciferase expression in Shh-LIGHTII cells. An extension of this study to F-ring-modified structures shows the necessity of a rigidly positioned nitrogen atom for bioactivity as well as the presence of the C21 methyl group for acid stability and bioactivity.

scholarly journals Design, synthesis, and biological evaluation of estrone-derived hedgehog signaling inhibitors

Tetrahedron ◽  
2011 ◽  
Vol 67 (52) ◽  
pp. 10261-10266 ◽  
Author(s):  
Jeffrey D. Winkler ◽  
André K. Isaacs ◽  
Chaomei Xiang ◽  
Valérie Baubet ◽  
Nadia Dahmane
Keyword(s):  
Hedgehog Signaling ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Signaling Inhibitors ◽  
Synthesis And Biological Evaluation

Synthesis and biological evaluation of suffrutines A, B and their N-fused analogues

2020 ◽  
Vol 7 (9) ◽  
pp. 1122-1131
Author(s):  
Zefeng Zhu ◽  
Chun Chen ◽  
Jingxing Jiang ◽  
Qianzhong Zhang ◽  
Zhibo Du ◽  
...  
Keyword(s):  
Nitrogen Atom ◽  
Anticancer Activity ◽  
Biological Evaluation ◽  
Biological Tests ◽  
Synthesis And Biological Evaluation ◽  
Structure Confirmation

The synthesis, structure confirmation, stability and isomerization features of suffrutines A, B and their N-fused analogues were reported. Biological tests showed that the introduction of nitrogen atom might be beneficial to the anticancer activity.

Total synthesis and biological evaluation of oscillatoxin D, E, and F

2021 ◽  
Author(s):  
Yusuke Araki ◽  
Yusuke Hanaki ◽  
Masaki Kita ◽  
Koutaro Hayakawa ◽  
Kazuhiro Irie ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Cell Line ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Marine Cyanobacteria ◽  
Methyl Group ◽  
Synthetic Strategy ◽  
Target Molecules ◽  
Synthesis And Biological Evaluation

Abstract Oscillatoxins (OTXs) and aplysiatoxins (ATXs) are biosynthetically related polyketides produced by marine cyanobacteria. We previously developed a synthetic route to phenolic O-methyl analogs of OTX-D and 30-methyl-OTX-D during collective synthesis of these natural products. According to our synthetic strategy, we achieved total synthesis of OTX-D, 30-methyl-OTX-D, OTX-E, and OTX-F by deprotecting the O-methyl group in an earlier intermediate, and determined their biological activities. Although OTX-D and 30-methyl-OTX-D have been reported to show anti-leukemic activity against L1210 cell line, we found that their cytotoxicity in vitro against this cell line is relatively weak (IC50: 29–52 μM). In contrast, OTX-F demonstrated cell line-selective anti-proliferative activity against DMS-114 lung cancer cells, which implies that OTXs target as yet unknown target molecules as part of this unique activity.

Synthesis and biological evaluation of N-(2-fluorophenyl)-2β-deoxyfuconojirimycin acetamide as a potent inhibitor for α-l-fucosidases

2013 ◽  
Vol 21 (21) ◽  
pp. 6565-6573 ◽  
Author(s):  
Atsushi Kato ◽  
Toru Okaki ◽  
Syohei Ifuku ◽  
Kasumi Sato ◽  
Yuki Hirokami ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Biological Evaluation ◽  
Synthesis And Biological Evaluation

scholarly journals Synthesis and Biological Evaluation of Novel Jatrorrhizine Derivatives with Amino Groups Linked at the 3-Position as Inhibitors of Acetylcholinesterase

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaofei Jiang ◽  
Nengling Zhang ◽  
Nanqian Xiong ◽  
Yi Liu ◽  
Jianfeng Cao ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Biological Evaluation ◽  
Lead Compound ◽  
Amino Groups ◽  
Coptis Chinensis ◽  
Inhibitor Activity ◽  
Active Constituents ◽  
Potential Inhibitors ◽  
Synthesis And Biological Evaluation

Jatrorrhizine was considered as one of the active constituents of Coptis chinensis Franch. Herein, jatrorrhizine derivatives with substituted amino groups linked at the 3-position were designed, synthesized, and biologically evaluated as inhibitors of acetylcholinesterase. Jatrorrhizine derivatives inhibited the activity of acetylcholinesterase (AChE) to a greater extent than the lead compound jatrorrhizine. All these jatrorrhizine derivatives were proved to be potent inhibitors of acetylcholinesterase (AChE) with submicromolar IC50 values, but less sensitive to butyrylcholinesterase (BuChE), which suggests that these jatrorrhizine derivatives are selective for AChE/BuChE. Compound 3g gave the most potent inhibitor activity for AChE (IC50 = 0.301 μM), which is greater than the lead compound jatrorrhizine. All these results demonstrated that these jatrorrhizine derivatives are potential inhibitors for AChE.

Critical Importance of the Nine-Membered F Ring of Ciguatoxin for Potent Bioactivity: Total Synthesis and Biological Evaluation of F-Ring-Modified Analogues

2008 ◽  
Vol 120 (45) ◽  
pp. 8739-8742 ◽  
Author(s):  
Masayuki Inoue ◽  
Nayoung Lee ◽  
Keisuke Miyazaki ◽  
Toyonobu Usuki ◽  
Shigeru Matsuoka ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Biological Evaluation ◽  
Critical Importance ◽  
F Ring ◽  
Synthesis And Biological Evaluation

Synthesis and biological evaluation of SANT-2 and analogues as inhibitors of the hedgehog signaling pathway

2009 ◽  
Vol 17 (14) ◽  
pp. 4943-4954 ◽  
Author(s):  
Anita Büttner ◽  
Katrin Seifert ◽  
Thomas Cottin ◽  
Vasiliki Sarli ◽  
Lito Tzagkaroulaki ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Biological Evaluation ◽  
Hedgehog Signaling Pathway ◽  
Synthesis And Biological Evaluation
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