Evidence for the Rapid Conversion of Stephacidin B into the Electrophilic Monomer Avrainvillamide in Cell Culture

Wulff, Jeremy E.; Herzon, Seth B.; Siegrist, Romain; Myers, Andrew G.

doi:10.1021/ja0690971

Cited by 53 publications

(39 citation statements)

References 20 publications

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“…Recent studies conducted by Myers et al suggest that the growth-inhibitory activity of stephacidin B is a result of retrodimerization to form the monomer avrainvillamide, which may then act as a novel Michael acceptor via the α,β-unsaturated nitrone group. 52 …”

Section: Stephacidins and Notoamidesmentioning

confidence: 99%

Fungal Origins of the Bicyclo[2.2.2]diazaoctane Ring System of Prenylated Indole Alkaloids

et al. 2012

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Over eight different families of natural products consisting of nearly 70 secondary metabolites that contain the bicyclo[2.2.2]diazaoctane ring system have been isolated from various Aspergillus, Penicillium, and Malbranchea species. Since 1968, these secondary metabolites have been the focus of numerous biogenetic, synthetic, taxonomic, and biological studies and, as such, have made a lasting impact across multiple scientific disciplines. This review covers the isolation, biosynthesis, and biological activity of these unique secondary metabolites containing the bridging bicyclo[2.2.2]diazaoctane ring system. Furthermore, the diverse fungal origin of these natural products is closely examined and, in many cases, updated to reflect the currently accepted fungal taxonomy.

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Section: Stephacidins and Notoamidesmentioning

confidence: 99%

Fungal Origins of the Bicyclo[2.2.2]diazaoctane Ring System of Prenylated Indole Alkaloids

et al. 2012

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“…Similarly, the anticancer activity of the dimeric alkaloid stephacidin B can be mimicked by a monomeric alkaloid, avrainvillamide, which in turn can be mimicked by much simpler analogues41. Synthetic studies on the highly complex molecule halichondrin B led to the discovery that its antitumour activity was contained in one part of the structure42.…”

Section: Some Parts Are Greater Than the Wholementioning

confidence: 99%

Synthesis at the molecular frontier

Wender¹,

Miller²

2009

Nature

513

289

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Driven by remarkable advances in the understanding of structure and reaction mechanisms, organic synthesis will be increasingly directed to producing bioinspired and newly designed molecules. Molecular evolution on Earth over the past 3.8 billion years has produced an extraordinary library of chemical structures, unsurpassed in number, diversity and function. Each structure is a treasure-trove of information and inspiration, a molecular textbook encoded in the language of chemistry. Collectively, these molecules comprise the chemical genome of our planet, and represent a universe ripe for exploration. With modern analytical tools, each of these structural tomes can now be read, enabling an understanding of how structure relates to function. More significantly, we can now use organic synthesis not only to make copies of these molecules, but also to prepare bioinspired or designed compounds, some with functions unheard of in the natural world -compounds that will influence, if not shape, every facet of our existence.Our emerging molecular literacy is creating a revolution that will transform our world. The ability to design, create and control molecules has opened a vast frontier of research and an age of unprecedented opportunity. Scientists from every background are being drawn to this molecular frontier, creating a melting pot of disciplinary fusions and the resultant ability to address problems that transcend the boundaries of individual fields. From molecular biology to molecular computing, molecular medicine, molecular (nano) technology and even molecular gastronomy, science is becoming increasingly integrated and 'molecularized'.Chemists have been laying the foundations for this molecular revolution for the past two centuries. Before that, nature's archive was the sole or primary source of chemicals used by humans. This has now changed. Through extraordinarily innovative advances in tools, theories and methods, synthesis has provided a reliable supply of many natural compounds as well as others created by design. Indeed the question of whether a molecule from nature could be made is increasingly giving way to whether it could be made in a way that impacts on supply and science. Of increasing importance now is the question of what molecules to make. Naturally occurring molecules are produced in their ecosystems for uses other than what we seek or need. Their activities in humans are thus serendipitous and unoptimized but provide a rich source of information and inspiration. We are now on the cusp of a period in which we can use this inspiration to design molecules with superior or new functions and make them in increasingly efficient, practical and environmentally friendly ways [1][2][3][4][5][6][7][8][9][10][11] .

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“…As of today, only two strategies have been followed for the design of new HSP60 inhibitors [127]. One strategy aims at targeting HSP60 cysteine residues either as oxidizable sites [128] or for covalent binding, presumably through interaction with an electrophilic compound [129][130][131]. The other approach targets ATP binding and hydrolysis sites-functions, thus affecting those ATP-dependent conformational changes of HSP60 which are crucial for the protein folding function [132][133][134].…”

Section: Hsp60 Inhibitors and Their Potential Applications In Alzheimmentioning

confidence: 99%

“…4.7) [127]. For instance, avrainvillamide (8), can alkylate HSP60's cysteine residues through the electrophilic 3-alkylidene-3H-indole 1-oxide moiety [131]; however, its activity in inhibiting HSP60 functions has not been demonstrated yet.…”

Section: Hsp60 Inhibitors and Their Potential Applications In Alzheimmentioning

confidence: 99%

Chaperonotherapy for Alzheimer’s Disease: Focusing on HSP60

Cappello

Gammazza

Vilasi

et al. 2015

Heat Shock Proteins

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Evidence for the Rapid Conversion of Stephacidin B into the Electrophilic Monomer Avrainvillamide in Cell Culture

Cited by 53 publications

References 20 publications

Fungal Origins of the Bicyclo[2.2.2]diazaoctane Ring System of Prenylated Indole Alkaloids

Fungal Origins of the Bicyclo[2.2.2]diazaoctane Ring System of Prenylated Indole Alkaloids

Synthesis at the molecular frontier

Chaperonotherapy for Alzheimer’s Disease: Focusing on HSP60

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