Potent Antitumor Natural Product Research Articles

Tumor selective self-assembled nanomicelles of carbohydrate-epothilone B conjugate for targeted chemotherapy

Epothilone B (Epo B) is a potent antitumor natural product with sub-nanomolar anti-proliferation action against several human cancer cells. However, poor selectivity to tumor cells and unacceptable therapeutic windows of Epo B and its analogs are the major obstacles to their development into clinical drugs. Herein, we present self-assembled nanomicelles based on an amphiphilic carbohydrate-Epo B conjugate that is inactive until converted to active Epo B within the tumor. Four Epo B-Rhamnose conjugates linked via two linkers containing a disulfide bond that is sensitive to GSH were synthesized. Conjugate 34 can self-assemble into nanomicelles with a high concentration of Rha on the surface, allowing for better tumor targeting. After internalization by cancer cells, the disulfide bond can be cleaved in the presence of high levels of GSH to release active Epo B, thereby exhibiting significant anticancer efficiency and selectivity in vitro and in vivo.

New and Highly Potent Antitumor Natural Products from Marine-Derived Fungi: Covering the Period from 2003 to 2012

This review covers the 2003-2012 literature data published for antitumor natural products from marine-derived fungi. The focus is on new and highly potent cytotoxic compounds, together with details related to the relevant fungal species. It describes 22 promising bioactives, originating mainly from symbiotic fungi. The chemical structures of all highlighted organic molecules are briefly discussed.

ChemInform Abstract: Practical Synthesis of DOPA Derivative for Biosynthetic Production of Potent Antitumor Natural Products, Saframycins and Ecteinascidin 743.

AbstractThe features in the synthesis of title compound (X) are higher reproducibility, more facile handling without needs of setting dry and inert conditions, easy purification of (X) by recrystallization, and much better scalability.

Practical Synthesis of DOPA Derivative for Biosynthetic Production of Potent Antitumor Natural Products, Saframycins and Ecteinascidin 743

The features in the synthesis of title compound (X) are higher reproducibility, more facile handling without needs of setting dry and inert conditions, easy purification of (X) by recrystallization, and much better scalability.

New Applications of PhI(OAc)2 in Synthesis: Total Synthesis and SAR Development of Potent Antitumor Natural Product Psymberin/Irciniastatin A

A novel PhI(OAc) 2 -mediated oxidative cyclization reaction is discovered for the synthesis of α-oxy N-acyl aminals and hemiaminals in good yields from readily synthesized N-acyl enamines. This methodology represents a cascade process to construct the core structure of the pederin family of natural products. The total synthesis of psymberin, a member of the pederin family, is accomplished using this ring-closure reaction as the key step. This new method is further showcased in the preparation of advanced psymberin analogues. The biological data of these analogues are presented. 1 Introduction 2 Methodology Development 3 Total Synthesis of Psymberin 4 Synthesis of Psymberin Analogues: The Discovery of C11-Deoxypsymberin 5 Conclusion.

Meayamycin inhibits pre–messenger RNA splicing and exhibits picomolar activity against multidrug-resistant cells

FR901464 is a potent antitumor natural product that binds to the splicing factor 3b complex and inhibits pre-mRNA splicing. Its analogue, meayamycin, is two orders of magnitude more potent as an antiproliferative agent against human breast cancer MCF-7 cells. Here, we report the picomolar antiproliferative activity of meayamycin against various cancer cell lines and multidrug-resistant cells. Time-dependence studies implied that meayamycin may form a covalent bond with its target protein(s). Meayamycin inhibited pre-mRNA splicing in HEK-293 cells but not alternative splicing in a neuronal system. Meayamycin exhibited specificity toward human lung cancer cells compared with nontumorigenic human lung fibroblasts and retained picomolar growth-inhibitory activity against multidrug-resistant cells. These data suggest that meayamycin is a useful chemical probe to study pre-mRNA splicing in live cells and is a promising lead as an anticancer agent.

Chemo- and regioselective hydroboration of Δ 14,15 in certain cephalostatin analogue

The symmetrical diketone II, which can be synthesized in gram scale using a well established method, was used as a starting material to prepare the 11α-methoxy ketomethylene VI. This is in continuation of our study aiming at the synthesis of multi-hydroxylated cephalostatin analogues, as for example cephalostatin 1 I, a potent anti-tumor natural product. Compound VI underwent chemo- and regioselective hydroboration reaction at only one of Δ 14,15 double bonds furnishing compound IX as a major product in a fair yield.

A new strategy for the stereoselective introduction of steroid side chain via alpha-alkoxy vinyl cuprates: total synthesis of a highly potent antitumor natural product OSW-1.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTA New Strategy for the Stereoselective Introduction of Steroid Side Chain via α-Alkoxy Vinyl Cuprates: Total Synthesis of a Highly Potent Antitumor Natural Product OSW-11Wensheng Yu and Zhendong JinView Author Information Division of Medicinal and Natural Products Chemistry College of Pharmacy, The University of Iowa Iowa City, Iowa 52242 Cite this: J. Am. Chem. Soc. 2001, 123, 14, 3369–3370Publication Date (Web):March 14, 2001Publication History Received28 November 2000Published online14 March 2001Published inissue 1 April 2001https://doi.org/10.1021/ja004098tCopyright © 2001 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views2095Altmetric-Citations65LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (51 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Anions,Chemical synthesis,Ethers,Steroids,Vinyl Get e-Alerts

ChemInform Abstract: Total Synthesis of Epothilone A.

[reaction: see text]Epothilones A (1) and B (2) are potent antitumor natural products with a Taxol-like mechanism of action. A total synthesis of epothilone A (1) is reported, which utilized chiral silane-based bond construction methodology to introduce the key C-6 and C-7 stereocenters of fragment 4. The C-15 stereocenter of fragment 5 was established by a lipase-mediated kinetic resolution. The fragments were assembled with a Suzuki coupling reaction and an aldol condensation and cyclized with a Yamaguchi-type macrolactonization reaction.

Total synthesis of epothilone A.

[reaction: see text]Epothilones A (1) and B (2) are potent antitumor natural products with a Taxol-like mechanism of action. A total synthesis of epothilone A (1) is reported, which utilized chiral silane-based bond construction methodology to introduce the key C-6 and C-7 stereocenters of fragment 4. The C-15 stereocenter of fragment 5 was established by a lipase-mediated kinetic resolution. The fragments were assembled with a Suzuki coupling reaction and an aldol condensation and cyclized with a Yamaguchi-type macrolactonization reaction.

Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity.

The proteasome regulates cellular processes as diverse as cell cycle progression and NF-kappaB activation. In this study, we show that the potent antitumor natural product epoxomicin specifically targets the proteasome. Utilizing biotinylated-epoxomicin as a molecular probe, we demonstrate that epoxomicin covalently binds to the LMP7, X, MECL1, and Z catalytic subunits of the proteasome. Enzymatic analyses with purified bovine erythrocyte proteasome reveal that epoxomicin potently inhibits primarily the chymotrypsin-like activity. The trypsin-like and peptidyl-glutamyl peptide hydrolyzing catalytic activities also are inhibited at 100- and 1,000-fold slower rates, respectively. In contrast to peptide aldehyde proteasome inhibitors, epoxomicin does not inhibit nonproteasomal proteases such trypsin, chymotrypsin, papain, calpain, and cathepsin B at concentrations of up to 50 microM. In addition, epoxomicin is a more potent inhibitor of the chymotrypsin-like activity than lactacystin and the peptide vinyl sulfone NLVS. Epoxomicin also effectively inhibits NF-kappaB activation in vitro and potently blocks in vivo inflammation in the murine ear edema assay. These results thus define epoxomicin as a novel proteasome inhibitor that likely will prove useful in exploring the role of the proteasome in various in vivo and in vitro systems.

The enantioselective total synthesis of the antitumor macrolide natural product rhizoxin D

A convergent, enantioselective total synthesis of rhizoxin D (didesepoxy-rhizoxin), a potent antitumor natural product, was achieved via three critical olefinations, including a Horner-Emmons macrocyclization.