The Experts below are selected from a list of 228 Experts worldwide ranked by ideXlab platform
Zhanzhu Liu - One of the best experts on this subject based on the ideXlab platform.
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Design, synthesis and cytotoxicity of novel hexacyclic Saframycin-ecteinascidin analogs.
Organic & biomolecular chemistry, 2020Co-Authors: Lu Xiangran, Baohe Guan, Xuan Pan, Zhanzhu LiuAbstract:Two series of novel hexacyclic skeletons and their thirty-four derivatives were prepared from L-tryptophan and L-DOPA. The cytotoxicities of these compounds were tested against four human cancer cell lines HCT-116, HepG2, BGC-823 and A2780. Compounds with the tetrahydro-β-carboline moiety in the left-half of the hexacyclic skeleton showed more potent cytotoxicity with IC50 values in the range of 10−7–10−9 M. Compound 20 with the 4-methoxybenzamide side chain showed potent cytotoxicity towards HepG2 with an IC50 value of 1.32 nM. Compounds 29 and 30 with 2-pyridine amide and (2E)-3-(3-thifluoromethyl-phenyl)acrylic amide side chains showed selective cytotoxicity towards A2780 with IC50 values of 1.73 nM and 7 nM, respectively.
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synthesis and cytotoxicity of 3 aryl acrylic amide derivatives of the simplified Saframycin ecteinascidin skeleton prepared from l dopa
European Journal of Medicinal Chemistry, 2013Co-Authors: Ju Guo, Wenfang Dong, Nan Wang, Wei Liu, Zheng Yan, Zhanzhu LiuAbstract:Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified Saframycin-ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from L-dopa. The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7402, BGC-803, A549, A2780, MCF-7, MX-1, and MDA-MB-231. Most of these compounds exhibited potent antitumor activity, and a preliminary structure-activity relationship (SAR) was discussed. Compound 28 with 3-thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA-MB-231 cell line with the IC50 value of 50 nM.
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asymmetric synthesis and cytotoxicity of Saframycin a analogues
ChemInform, 2012Co-Authors: Wenfang Dong, Nan Wang, Wei Liu, Zheng Yan, Xiangwei Liao, Baohe Guan, Zhanzhu LiuAbstract:A series of (-)-Saframycin A analogues (I) are prepared from L-tyrosine in 24 steps and evaluated for their in vitro cytotoxicity against a panel of ten human tumor cell lines.
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Asymmetric Synthesis and Cytotoxicity of (‐)‐Saframycin A Analogues.
ChemInform, 2012Co-Authors: Wenfang Dong, Nan Wang, Wei Liu, Zheng Yan, Xiangwei Liao, Baohe Guan, Zhanzhu LiuAbstract:A series of (-)-Saframycin A analogues (I) are prepared from L-tyrosine in 24 steps and evaluated for their in vitro cytotoxicity against a panel of ten human tumor cell lines.
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Asymmetric synthesis and cytotoxicity of (-)-Saframycin A analogues.
European journal of medicinal chemistry, 2012Co-Authors: Wenfang Dong, Nan Wang, Wei Liu, Zheng Yan, Xiangwei Liao, Baohe Guan, Zhanzhu LiuAbstract:(-)-Saframycin A and its nineteen analogues were prepared from L-tyrosine in 24 steps, and their structures were confirmed through NMR and HRMS. The cytotoxicities of these compounds were tested against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-803, Hela, HELF and KB cell lines. The IC(50) values of the cytotoxicity of most compounds were at the level of nM. Compound 7d with 2-furan amide side chain showed the most potent cytotoxicity of all these compounds with an average IC(50) value of 6.06 nM.
Andrew G. Myers - One of the best experts on this subject based on the ideXlab platform.
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Identification of GAPDH as a protein target of the Saframycin antiproliferative agents
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Chengguo Xing, Jacob R. Laporte, Joseph K. Barbay, Andrew G. MyersAbstract:Saframycin A (SafA) is a member of a class of natural products with potent antiproliferative effects in leukemia- and tumor-derived cells. This activity is frequently conjectured to derive from the ability of Saframycins to covalently modify duplex DNA. We used a DNA-linked affinity purification technique to identify GAPDH as a protein target of DNA–small molecule adducts of several members of the Saframycin class. Nuclear translocation of GAPDH occurs upon treatment of cancer cells with Saframycins, and depletion of cellular GAPDH levels by small interfering RNA transfection confers drug resistance. Roeder and coworkers have recently suggested that GAPDH is a key transcriptional coactivator necessary for entry into S phase. Our data suggest that GAPDH is also capable of forming a ternary complex with Saframycin-related compounds and DNA that induces a toxic response in cells. These studies implicate a previously unknown molecular mechanism of antiproliferative activity and, given that one member of the Saframycin class has shown efficacy in cancer treatment, suggest that GAPDH may be a potential target for chemotherapeutic intervention.
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A Solid-Supported, Enantioselective Synthesis Suitable for the Rapid Preparation of Large Numbers of Diverse Structural Analogues of (−)-Saframycin A
Journal of the American Chemical Society, 2002Co-Authors: Andrew G. Myers, Brian A. LanmanAbstract:A 10-step solid-supported, enantioselective synthesis suitable for the rapid preparation of large numbers of diverse structural analogues of Saframycin A is described. The synthetic route, which bears analogy to solid-phase peptide synthesis, involves the directed condensation of N-protected α-amino aldehyde reactants. A novel dual linker was developed for attachment of intermediates to the solid support via a C-protective group, a substituted morpholino nitrile derivative. The route employs a novel diastereospecific cyclorelease mechanism, supports structural variation at multiple sites in the Saframycin core, and obviates the need for chromatographic purification of the products or any intermediate. To demonstrate the feasibility of structural variation at multiple sites, a matrix of 16 Saframycin A analogues was prepared by parallel synthesis with simultaneous variation of two sites. This work is notable not only as a preliminary step toward large-scale library construction but also as an example of th...
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a solid supported enantioselective synthesis suitable for the rapid preparation of large numbers of diverse structural analogues of Saframycin a
Journal of the American Chemical Society, 2002Co-Authors: Andrew G. Myers, Brian A. LanmanAbstract:A 10-step solid-supported, enantioselective synthesis suitable for the rapid preparation of large numbers of diverse structural analogues of Saframycin A is described. The synthetic route, which bears analogy to solid-phase peptide synthesis, involves the directed condensation of N-protected α-amino aldehyde reactants. A novel dual linker was developed for attachment of intermediates to the solid support via a C-protective group, a substituted morpholino nitrile derivative. The route employs a novel diastereospecific cyclorelease mechanism, supports structural variation at multiple sites in the Saframycin core, and obviates the need for chromatographic purification of the products or any intermediate. To demonstrate the feasibility of structural variation at multiple sites, a matrix of 16 Saframycin A analogues was prepared by parallel synthesis with simultaneous variation of two sites. This work is notable not only as a preliminary step toward large-scale library construction but also as an example of th...
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Transcriptional Response Pathways in a Yeast Strain Sensitive to Saframycin A and a More Potent Analog: Evidence for a Common Basis of Activity
Chemistry & biology, 2002Co-Authors: Alleyn T. Plowright, Scott E. Schaus, Andrew G. MyersAbstract:Abstract Saframycin A (SafA) is a natural product that inhibits human cancer cell proliferation. Its synthetic analog, QAD, is a more potent inhibitor of these cells. SafA does not affect wild-type yeast, but it does inhibit growth of the strain CCY333 (Δ PDR1/PDR3/ERG6 ) (IC 50 = 0.9 μM). QAD is also a more effective inhibitor of CCY333 growth (IC 50 = 0.4 μM). Transcription profiling of SafA- and QAD-treated CCY333 cultures showed that both drugs generated nearly identical profiles, with altered expression levels (≥2-fold) of more than 240 genes. Both agents induced the overexpression of genes involved in glycolysis, oxidative stress, and protein degradation and repressed genes encoding histones, biosynthetic enzymes, and the cellular import machinery. Significantly, neither drug affected the expression of known DNA-damage repair genes, as might have been expected if their primary mechanism of action involved the covalent modification of DNA.
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One-step construction of the pentacyclic skeleton of Saframycin A from a "Trimer" of alpha-amino aldehydes.
Organic letters, 2000Co-Authors: Andrew G. Myers, Daniel W. KungAbstract:The entire skeleton of the Saframycin antitumor antibiotics is assembled in one remarkable transformation (8 --> 9) from an N-linked oligomer of three alpha-amino aldehyde components, a reaction pathway that may parallel the biosynthetic route to the Saframycins.
Naoki Saito - One of the best experts on this subject based on the ideXlab platform.
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Chemical Research on Antitumor Isoquinoline Marine Natural Products and Related Compounds.
Chemical & pharmaceutical bulletin, 2021Co-Authors: Naoki SaitoAbstract:The biologically active, naturally occurring 1,2,3,4-tetrahydroisoquinoline-quinone (THIQ) family members isolated from Actinomycetes and marine organisms have been studied thoroughly over the past five decades. Among them, marine natural products along with their reduced compounds, such as renieramycins and ecteinascidins, have attracted interest due to their fantastic structures and meager availability in nature as well as their potent antitumor profiles. As part of our search for new anticancer metabolites through the isolation and characterization of anticancer THIQ compounds from Thai marine animals, we have developed a fascinating THIQ natural product chemistry and medicinal chemistry based on knowledge of the chemistry of Saframycin antibiotics as well as their isolation, characterization, transformation, partial synthesis, and total synthesis. This review mainly presents our contributions during 1999-2019 to the field of research on biologically active renieramycin along with ecteinascidin marine natural products.
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a stereocontrolled total synthesis of Saframycin a
Tetrahedron, 2018Co-Authors: Shinya Kimura, Naoki SaitoAbstract:Abstract A thirteen-step total synthesis of (±)-Saframycin A from a tricyclic lactam intermediate is described. The key step of this total synthesis is the stereocontrolled construction of a pentacyclic Saframycin framework via a modified Pictet-Spengler type cyclization generating a bis-carboxylic acid ester derivative, followed by decarboxylation. The cytotoxicity profiles are also presented.
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A stereocontrolled total synthesis of (±)-Saframycin A
Tetrahedron, 2018Co-Authors: Shinya Kimura, Naoki SaitoAbstract:Abstract A thirteen-step total synthesis of (±)-Saframycin A from a tricyclic lactam intermediate is described. The key step of this total synthesis is the stereocontrolled construction of a pentacyclic Saframycin framework via a modified Pictet-Spengler type cyclization generating a bis-carboxylic acid ester derivative, followed by decarboxylation. The cytotoxicity profiles are also presented.
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Preparation of tricyclic lactam model compounds of renieramycin and Saframycin anticancer natural products from common intermediate.
Chemical & pharmaceutical bulletin, 2013Co-Authors: Keiyo Nakai, Masashi Yokoya, Naoki SaitoAbstract:Tricyclic lactam model compounds of the left half (ABC ring) of renieramycin and Saframycin anticancer natural products were prepared from common intermediate 6a. Readily available alcohol 6a was converted into enamide 8, and this was followed by transformation into 6b through a hydrobromination reaction in a stereoselective manner. Some diastereomers at C-6 to C-11a of the tricyclic lactam model compounds having several functional groups at C-6 were prepared from 6a or 6b in good yields. We presented also an unexpected reductive acetylation of the p-quinone to produce the corresponding 3,4-dehydro derivative.
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synthesis of 1 2 3 4 5 6 7 10 octahydro 1 5 imino 7 10 dioxo 3 benzazocine 4 carbonitrile derivative and evaluation of antitumor activity related to Saframycin and renieramycin isoquinolinequinones
Heterocycles, 2006Co-Authors: Naoki Saito, Yu-ichi Koizumi, Kenichi Inamura, Akinori KuboAbstract:3-Benzyl-l,2,3,4,5,6,7,10-octahydro-9-methoxy-8,ll-dimethyl-7,10-dioxo-l,5-imino-3-benzazocine-4-carbonitrile (4) as a simple model of Saframycin A and renieramycin M is prepared and its cytotoxicity tested against three human cancer cell lines.
Wenfang Dong - One of the best experts on this subject based on the ideXlab platform.
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synthesis and cytotoxicity of 3 aryl acrylic amide derivatives of the simplified Saframycin ecteinascidin skeleton prepared from l dopa
European Journal of Medicinal Chemistry, 2013Co-Authors: Ju Guo, Wenfang Dong, Nan Wang, Wei Liu, Zheng Yan, Zhanzhu LiuAbstract:Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified Saframycin-ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from L-dopa. The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7402, BGC-803, A549, A2780, MCF-7, MX-1, and MDA-MB-231. Most of these compounds exhibited potent antitumor activity, and a preliminary structure-activity relationship (SAR) was discussed. Compound 28 with 3-thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA-MB-231 cell line with the IC50 value of 50 nM.
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Synthesis and cytotoxicity of 3-aryl acrylic amide derivatives of the simplified Saframycin–ecteinascidin skeleton prepared from l-dopa
European Journal of Medicinal Chemistry, 2013Co-Authors: Wenfang Dong, Nan WangAbstract:Abstract Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified Saframycin–ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from l -dopa. The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7402, BGC-803, A549, A2780, MCF-7, MX-1, and MDA-MB-231. Most of these compounds exhibited potent antitumor activity, and a preliminary structure–activity relationship (SAR) was discussed. Compound 28 with 3-thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA-MB-231 cell line with the IC 50 value of 50 nM.
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Synthesis and cytotoxicity of 3-aryl acrylic amide derivatives of the simplified Saframycin–ecteinascidin skeleton prepared from l-dopa
European Journal of Medicinal Chemistry, 2013Co-Authors: Wenfang Dong, Nan WangAbstract:Abstract Twenty four compounds with diversified 3-aryl acrylic amide side chains of the simplified Saframycin–ecteinascidin pentacyclic skeleton were synthesized via a 14-step stereospecific route starting from l -dopa. The cytotoxicities of these compounds were tested against eight human tumor cell lines including HCT-8, BEL-7402, BGC-803, A549, A2780, MCF-7, MX-1, and MDA-MB-231. Most of these compounds exhibited potent antitumor activity, and a preliminary structure–activity relationship (SAR) was discussed. Compound 28 with 3-thiophenyl acrylic amide side chain exhibited selective cytotoxicity against MDA-MB-231 cell line with the IC 50 value of 50 nM.
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asymmetric synthesis and cytotoxicity of Saframycin a analogues
ChemInform, 2012Co-Authors: Wenfang Dong, Nan Wang, Wei Liu, Zheng Yan, Xiangwei Liao, Baohe Guan, Zhanzhu LiuAbstract:A series of (-)-Saframycin A analogues (I) are prepared from L-tyrosine in 24 steps and evaluated for their in vitro cytotoxicity against a panel of ten human tumor cell lines.
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Asymmetric Synthesis and Cytotoxicity of (‐)‐Saframycin A Analogues.
ChemInform, 2012Co-Authors: Wenfang Dong, Nan Wang, Wei Liu, Zheng Yan, Xiangwei Liao, Baohe Guan, Zhanzhu LiuAbstract:A series of (-)-Saframycin A analogues (I) are prepared from L-tyrosine in 24 steps and evaluated for their in vitro cytotoxicity against a panel of ten human tumor cell lines.
Brian A. Lanman - One of the best experts on this subject based on the ideXlab platform.
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A Solid-Supported, Enantioselective Synthesis Suitable for the Rapid Preparation of Large Numbers of Diverse Structural Analogues of (−)-Saframycin A
Journal of the American Chemical Society, 2002Co-Authors: Andrew G. Myers, Brian A. LanmanAbstract:A 10-step solid-supported, enantioselective synthesis suitable for the rapid preparation of large numbers of diverse structural analogues of Saframycin A is described. The synthetic route, which bears analogy to solid-phase peptide synthesis, involves the directed condensation of N-protected α-amino aldehyde reactants. A novel dual linker was developed for attachment of intermediates to the solid support via a C-protective group, a substituted morpholino nitrile derivative. The route employs a novel diastereospecific cyclorelease mechanism, supports structural variation at multiple sites in the Saframycin core, and obviates the need for chromatographic purification of the products or any intermediate. To demonstrate the feasibility of structural variation at multiple sites, a matrix of 16 Saframycin A analogues was prepared by parallel synthesis with simultaneous variation of two sites. This work is notable not only as a preliminary step toward large-scale library construction but also as an example of th...
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a solid supported enantioselective synthesis suitable for the rapid preparation of large numbers of diverse structural analogues of Saframycin a
Journal of the American Chemical Society, 2002Co-Authors: Andrew G. Myers, Brian A. LanmanAbstract:A 10-step solid-supported, enantioselective synthesis suitable for the rapid preparation of large numbers of diverse structural analogues of Saframycin A is described. The synthetic route, which bears analogy to solid-phase peptide synthesis, involves the directed condensation of N-protected α-amino aldehyde reactants. A novel dual linker was developed for attachment of intermediates to the solid support via a C-protective group, a substituted morpholino nitrile derivative. The route employs a novel diastereospecific cyclorelease mechanism, supports structural variation at multiple sites in the Saframycin core, and obviates the need for chromatographic purification of the products or any intermediate. To demonstrate the feasibility of structural variation at multiple sites, a matrix of 16 Saframycin A analogues was prepared by parallel synthesis with simultaneous variation of two sites. This work is notable not only as a preliminary step toward large-scale library construction but also as an example of th...
