AntibioticsAnthraquinone-fusedSynthesisPrecursorsCyclizationWarheadCyclisationBiosynthesisBiosyntheticSpecificityBergmanCompoundsMoleculesReactivePotentYieldsCitationNaturallyAcidAgentsCoreDesignUniqueProduceCyclizationsSelf-sacrificeResistanceCleavageProteinsGeneFunctionalMechanismsGroupNaturalActive
Antibiotics7
- Enediynes are most notable for their limited use as antitumor antibiotics (known as enediyne anticancer antibiotics). (wikipedia.org)
- Several of the naturally occurring members of the enediyne family of antibiotics have entered clinical trials, and this has prompted the design of synthetic enediynes, where the enediyne 'warhead' is conjugated to a targeted delivery vehicle. (eurekaselect.com)
- Of all recently discovered antibiotics, the natural enediyne antibiotics possibly show the most promise as prospective drugs for the treatment of various forms of cancer. (bgsu.edu)
- Unfortunately, low selectivity and high general toxicity of natural enediynes, as well as designed compounds based on essential structural features of natural enediyne antibiotics, prevented their use in clinical practice thus far. (bgsu.edu)
- The importance of the Bergmann cyclisation reaction in the mode of action of anti-tumour enediyne antibiotics such as calicheamicin- alpha and the neocarzinostatins provided the starting point for this collaborative project for which Dr David Smith is the principal investigator. (exeter.ac.uk)
- In this note the basics of enediyne class of natural and designed antitumor antibiotics, their history of discovery. (web.app)
- The authors were specifically interested in the products from the radical cleavage of oligonucleotides by DNA targeting molecules like bleomycin, enediyne antibiotics and transition metal complexes. (glenresearch.com)
Anthraquinone-fused1
- Here we report the isolation and structural elucidation of two new 10-membered anthraquinone-fused enediynes, yangpumicins (YPM) F ( 6 ) and G ( 7 ), together with five known congeners, YPM A-E ( 1 - 5 ), from Micromonospora yangpuensis DSM 45577. (figshare.com)
Synthesis1
- This review will describe ecent efforts using chemical synthesis to identify and improve the target specificity of designed enediynes, and to establish efficient methods to achieve prodrug activation. (eurekaselect.com)
Precursors3
- The enediyne cores are derived from linear, probably polyketide, precursors that consist of seven or eight head-to-tail coupled acetate units. (wikipedia.org)
- While oxacyclic enediyne 3.29 could not be prepared in a satisfactory yield and cyclic enediyne precursors 6.14 and 6.26 were found to be thermally unstable, carbocyclic diazodicarbonyl enediynes 4.18 and 5.15 were prepared in excellent synthetic yields. (bgsu.edu)
- My involvement in this project is from the synthetic angle, and I am currently directing and supervising the preparation of the required enediyne cyclisation precursors. (exeter.ac.uk)
Cyclization6
- Enediynes are triggered into a chemically active state via Bergman or Myers-Saito cyclization. (wikipedia.org)
- citation needed] Bergman cyclization restructures the enediyne ring into two smaller rings. (wikipedia.org)
- Some enediynes have an epoxide group attached to their ring, making Bergman cyclization unfavorable due to steric hindrance. (wikipedia.org)
- Myers-Saito cyclization is another triggering mechanism by which an enediyne warhead becomes a diradical. (wikipedia.org)
- citation needed] The cyclization of the enediyne functional group creates a transient reactive 1,4-benzenoid diradical that acts as a nucleophile and attacks electrophiles in order to achieve a more stable form. (wikipedia.org)
- Neocarzinostatin is an example of an enediyne that undergoes triggering via Myers-Saito cyclization. (wikipedia.org)
Warhead1
- A nine- or ten-membered ring containing a double bond between two triple bonds is termed the warhead of the enediyne. (wikipedia.org)
Cyclisation1
- Addition of a functionalised double bond was found to provide enough activation to the enediyne fragment to facilitate Bergman cyclisation of eleven-membered enediynes such as 5.16a , which was found to have a lifetime of 3 hours at 28° C. A series of DNA cleavage experiments showed that diazoenediynediones 4.18 and 5.15 exhibit moderate DNA cleavage activity upon irradiation at 350 nm. (bgsu.edu)
Biosynthesis1
- Due to the cytotoxicity of the enediyne chromophores, their biosynthesis is tightly regulated, although the regulatory mechanisms are still largely unclear. (wikipedia.org)
Biosynthetic2
- Enediyne assembly involves a highly conserved, iterative type I polyketide synthase (PKS) pathway Sequencing of enediyne gene clusters has confirmed the polyketide origin of the enediyne core, and elucidated the biosynthetic pathways and mechanisms of enediynes. (wikipedia.org)
- Differences in the biosynthetic pathways of enediynes are due to the different origins of the -yne carbons as well as differences in isotope incorporation patterns. (wikipedia.org)
Specificity2
- Consequently, research is being conducted to increase the specificity of enediyne toxicity. (wikipedia.org)
- These moieties can be either aromatic or sugars and define sequence specificity of DNA binding as well as the physical properties of the enediyne chromophores. (wikipedia.org)
Bergman1
- We have suggested to explore the feasibility of photochemical or thermal ring contraction reactions as tools to activate cyclic enediynes toward Bergman cycloaromatisation. (bgsu.edu)
Compounds3
- Enediynes are organic compounds containing two triple bonds and one double bond. (wikipedia.org)
- Muon spin rotation spectra of muoniated radicals of the enediyne compounds (E)- and (Z)-RCCCHCHCCR where R = -CH2CH2CH2CH3 are reported and the temperature variation of these spectra from 250 to 400 K investigated. (uea.ac.uk)
- Herein, we report an alternative method for alkylation of aromatics via nucleophilic addition of enolates of active methylene compounds to 1,4-dehydrobenzene diradicals derived from enediynes cyclodec-1,5-diyne-3-ene, benzo[3,4]-cyclodec-1,5-diyne-3-ene, and cyclohexeno[3,4]-cyclodec-1,5-diyne-3-ene. (escholarship.org)
Molecules2
- Enediyne natural products are among the most cytotoxic small molecules and thus excellent payload candidates for the development of antibody-drug conjugates (ADCs). (figshare.com)
- Here, we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne (EDY) molecules. (bvsalud.org)
Reactive1
- Following prodrug activation, the enediynes undergo cycloaromatization reactions resulting in formation of highly reactive diradical intermediates. (eurekaselect.com)
Potent2
- Members of the enediyne family all share a unique enediyne core that is the cause of their potent cytotoxicity. (wikipedia.org)
- The enediynes remain among the most potent antitumoral agents to have been discovered in the past decade. (eurekaselect.com)
Yields1
- The benzo-substituted enediyne produces slightly higher yields of alkylation products than do the other two enediynes, but the differences are not substantial. (escholarship.org)
Citation1
- citation needed] The nine-membered enediynes are also referred to as chromoproteins because they have an attached protein as a variable group. (wikipedia.org)
Naturally1
- There are fourteen naturally occurring enediynes. (wikipedia.org)
Acid1
- We have also found that Wolff rearrangement of a diazodicarbonyl moiety conjugated with the extended π-system of the enediyne fragment results in formation of highly enolised oxocarboxylic acid derivatives. (bgsu.edu)
Agents2
- Designed Enediyne Antitumor Agents, Frontiers in Medicinal Chemistry (2004) 1: 189. (eurekaselect.com)
- Some examples are enediynes (DNA-cleaving agents), 'click chemistry' tools and building blocks. (sigmaaldrich.com)
Core1
- Enediynes have been split into two sub-families: those with nine members in the core enediyne ring and those with ten-membered rings. (wikipedia.org)
Design1
- In an attempt to address this issue we employed an approach to pro-drug design that makes it possible not only to utilise stable and thus relatively non-toxic enediynes, but also to achieve a certain degree of control over their action. (bgsu.edu)
Unique1
- Finally, new horizons will be examined, including the use of post-cycloaromatized enediyne templates as recognition elements for unique DNA and RNA microenvironments. (eurekaselect.com)
Produce1
- Organisms that produce enediynes have been shown to protect themselves with a self-resistance mechanism that uses a self-sacrificing protein. (wikipedia.org)
Cyclizations1
- Reductive Bergman-Type Cyclizations of Cross-Conjugated Enediynes to Fulvene and Fulvalene Anions: The Role of the Substituent. (huji.ac.il)
Self-sacrifice1
- Structure-guided functional characterization of enediyne self-sacrifice resistance proteins, CalU16 and CalU19. (ouhsc.edu)
Resistance2
- Organisms that produce enediynes have been shown to protect themselves with a self-resistance mechanism that uses a self-sacrificing protein. (wikipedia.org)
- Two cancer drugs based on enediynes have been approved, but treatment resistance is a common problem for these compounds. (drugdiscoverynews.com)
Cleavage2
- it does not inhibit the action of all enediynes and it does not simply prevent the cleavage of DNA. (nature.com)
- Basak A, Kar M. ( 2008 ) Benzofused N-substituted cyclic enediynes: activation and DNA-cleavage potential. (academictree.org)
Proteins1
- These genes encode proteins that enable bacteria to resist a subset of enediynes known as tiancimycins, which are being explored as a base for new cancer drugs. (drugdiscoverynews.com)
Gene2
- Enediyne assembly involves a highly conserved, iterative type I polyketide synthase (PKS) pathway Sequencing of enediyne gene clusters has confirmed the polyketide origin of the enediyne core, and elucidated the biosynthetic pathways and mechanisms of enediynes. (wikipedia.org)
- In studies of the upstream region of the active pgk1 gene, we found that DNA damage produced by both enediynes was enhanced in sequences located between several transcription factor binding sites, while patterns of DNA damage within the binding sites were consistent with known drug binding modes and structures of the protein-DNA complexes. (nih.gov)
Functional2
- citation needed] The cyclization of the enediyne functional group creates a transient reactive 1,4-benzenoid diradical that acts as a nucleophile and attacks electrophiles in order to achieve a more stable form. (wikipedia.org)
- More differentiation comes from the attachment of various functional groups at different positions to the enediyne warheads during their maturation stage. (wikipedia.org)
Mechanisms1
- Two mechanisms by which bacteria can protect themselves from enediynes have previously been discovered, and in a recent Cell Chemical Biology study, Shen and his lab shared news of a third, which hinges on three genes: tnmS1, tnmS2 and tnmS3. (drugdiscoverynews.com)
Group4
- Some enediynes have an epoxide group attached to their ring, making Bergman cyclization unfavorable due to steric hindrance. (wikipedia.org)
- This mechanism requires the alkene of the enediyne to be part of a diene with a double bond in a variable group. (wikipedia.org)
- citation needed] The nine-membered enediynes are also referred to as chromoproteins because they have an attached protein as a variable group. (wikipedia.org)
- This protein is necessary for transport and stabilization of the enediyne group. (wikipedia.org)
Natural1
- The answer they discovered is tied to a class of natural products known as enediynes, which are yielded by bacteria referred to as actinomycetes, which are found in soil. (drugdiscoverynews.com)
Active3
- Enediynes are triggered into a chemically active state via Bergman or Myers-Saito cyclization. (wikipedia.org)
- Modulation of enediyne-induced DNA damage by chromatin structures in transcriptionally active genes. (nih.gov)
- ACS's Standard Package lets you stay up to date with C&EN, stay active in ACS, and save. (acs.org)