Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay

Dasari, Bhanudas; Jogula, Srinivas; Borhade, Ramdas; Sridhar, Balasubramanian; Chandrasekar, Gayathri; Kitambi, Satish Srinivas; Arya, Prabhat

doi:10.1021/ol3032297

Cited by 26 publications

(13 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our earlier approach,11a we reported a modular synthesis of 14‐membered macrocyclic compounds as glycohybrids that were derived from a pyran ring opening, followed by incorporation of the amino acid moiety, and finally, through application of the stitching technology 17. Herein, we propose a route to obtain C ‐linked β‐ and α‐glycosyl carboxyl esters 1.2 and 1.3 (Scheme ) that are known in the literature 18a.…”

Section: Resultsmentioning

confidence: 99%

Building a Macrocyclic Toolbox from C‐Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay

et al. 2013

Self Cite

View full text Add to dashboard Cite

We report the synthesis of four different types of macrocyclic‐derived glycohybrids from carbohydrates that have an amino acid moiety in the large‐ring skeleton. These macrocyclic glycohybrids were obtained from α‐C‐1H‐ and β‐C‐1H‐linked carbohydrates. In one series, we utilized ring‐closing metathesis as the “stitching technology” to obtain two different macrocycles, i.e., trans equatorial–axial C‐1H and C‐5H and cis axial–axial C‐1H and C‐5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial–axial C‐1H and C‐5H and cis axial–axial C‐1H and C‐5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial–axial orientation) between C‐1H and C‐5H showed activity and their other diastereomers (i.e., equatorial–axial C‐1H and C‐5 H) with a trans relationship did not show any effect.

show abstract

Section: Resultsmentioning

confidence: 99%

Building a Macrocyclic Toolbox from C‐Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…As an extension of this work, with the objective to explore macrocyclic chemical space, [26,27] we report herein a modular method that allowed us to incorporate different types of medium/large ring skeletons (see 1.2, 1.3, and 1.4; Scheme 1) into enantioenriched aminoindoline scaffold 1.1. There are several attractive features of aminoindoline scaffold 1.1 that make it an attractive starting point to incorporate various medium/large rings into the skeleton.…”

Section: Resultsmentioning

confidence: 99%

A Modular Approach to Build Macrocyclic Diversity in Aminoindoline Scaffolds Identifies Antiangiogenesis Agents from a Zebrafish Assay

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Angiogenesis is a hallmark behaviour of cancer that can be easily interrogated through phenotypic screens in zebrafish embryos. The groups of Arya and Kitambi have made a systematic study of the preparation of DOS libraries of macrocycles and their assessment as anti-angiogenic agents [44,45,46,47]. The choice of macrocyclic scaffolds was driven by their ubiquity in bioactive natural products, including those able to modulate protein-protein interactions, and by the relative paucity of this scaffold type in medicinal chemistry approaches [48].…”

Section: Dos As a Source Of New Chemical Tools For Cancer Biologymentioning

confidence: 99%

Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery

Collins

Jones

2014

Molecules

View full text Add to dashboard Cite

How can diversity-oriented strategies for chemical synthesis provide chemical tools to help shape our understanding of complex cancer pathways and progress anti-cancer drug discovery efforts? This review (surveying the literature from 2003 to the present) considers the applications of diversity-oriented synthesis (DOS), biology-oriented synthesis (BIOS) and associated strategies to cancer biology and drug discovery, summarising the syntheses of novel and often highly complex scaffolds from pluripotent or synthetically versatile building blocks. We highlight the role of diversity-oriented synthetic strategies in producing new chemical tools to interrogate cancer biology pathways through the assembly of relevant libraries and their application to phenotypic and biochemical screens. The use of diversity-oriented strategies to explore structure-activity relationships in more advanced drug discovery projects is discussed. We show how considering appropriate and variable focus in library design has provided a spectrum of DOS approaches relevant at all stages in anti-cancer drug discovery.

show abstract

Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay

Cited by 26 publications

References 42 publications

Building a Macrocyclic Toolbox from C‐Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay

Building a Macrocyclic Toolbox from C‐Linked Carbohydrates Identifies Antiangiogenesis Agents from Zebrafish Assay

A Modular Approach to Build Macrocyclic Diversity in Aminoindoline Scaffolds Identifies Antiangiogenesis Agents from a Zebrafish Assay

Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery

Contact Info

Product

Resources

About