53462-50-3Relevant articles and documents
Design, Synthesis, and Conformation-Activity Study of Unnatural Bridged Bicyclic Depsipeptides as Highly Potent Hypoxia Inducible Factor-1 Inhibitors and Antitumor Agents
Koike, Kota,Nagano, Masanobu,Ebihara, Masahiro,Hirayama, Tasuku,Tsuji, Mieko,Suga, Hiroaki,Nagasawa, Hideko
, p. 4022 - 4046 (2020/06/08)
By carrying out structural modifications based on the bicyclic peptide structure of echinomycin, we successfully synthesized various powerful antitumor derivatives. The ring conformation in the obtained compounds was restricted by cross-linking with an unnatural bond. The prepared derivatives were demonstrated to strongly suppress the hypoxia inducible factor (HIF)-1 transcriptional activation and hypoxia induction of HIF-1 protein expression. Particularly, alkene-bridged derivative 12 exhibited remarkably potent cytotoxicity (IC50 = 0.22 nM on the MCF-7 cell line) and HIF-1 inhibition (IC50 = 0.09 nM), which considerably exceeded those of echinomycin. Conformational analyses and molecular modeling studies revealed that the biological activities were enhanced following restriction of the conformation by cross-linking through a metabolically stable and rigid bridge bond. In addition, we proposed a new globular conformation stabilized by intramolecular πstacking that can contribute to the biological effects of bicyclic depsipeptides. The developments presented in the current study serve as a useful guide to expand the chemical space of peptides in drug discovery.
Synthesis and anticancer activity of the proposed structure of caldoramide, an N-peptidyltetramate from the cyanobacterium Caldora penicillata
Wunder, Anja,Rothemund, Matthias,Schobert, Rainer
supporting information, p. 5138 - 5142 (2018/04/16)
The structure proposed in the literature for caldoramide, a formal pentapeptide metabolite of the marine cyanobacterium Caldora penicillata, was synthesised in 12 steps and 16% yield (longest linear sequence from isoleucine) following the strategy of a stepwise consecutive extension of an N-oligopeptidyl chain on a tetramate anchor. The synthetic product differed from the natural isolate in optical rotation, some NMR data, and cytotoxicities. Its antiproliferative effect on three human cancer cell lines was distinctly lower than that of related dolastatin 10 and belamide A.
Total synthesis of modified pentapeptide, caldoramide
Anantoju, Kishore Kumar,Maringanti, Thirumala Chary,Syed Mohd., Baquer
supporting information, p. 2938 - 2940 (2018/06/29)
Total synthesis of modified pentapeptide, caldoramide, a cytotoxic linear pentapeptide from the marine cyanobacterium Caldora penicillate is described. Notable features of the route include the efficient preparation of three key fragments and final assemb
A practical approach to asymmetric synthesis of dolastatin 10
Zhou, Wen,Nie, Xiao-Di,Zhang, Yu,Si, Chang-Mei,Zhou, Zhu,Sun, Xun,Wei, Bang-Guo
, p. 6119 - 6131 (2017/08/02)
Dolastatin 10, an antineoplastic agent for cancer chemotherapy, is a linear peptide possessing N,N-dimethyl Val-OH, l-valine, (3R,4S,5S)-dolaisoleucine, (2R,3R,4S)-dolaproine and (S)-dolaphenine. Our efficient synthesis includes the following three key features: (1) SmI2-induced cross-coupling was employed to couple aldehyde 11 with (S)-N-tert-butanesulfinyl imine 12 to generate the required stereocenters of Dap (7); (2) asymmetric addition of chiral N-sulfinyl imine 10 provided a straightforward approach to the synthesis of the protected Doe ((S,S)-8); (3) a practical method to the key subunit Val-Dil (24a) has been established as an alternative synthetic route for the synthesis of this challenging chemical structure.
Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
Srinivasarao, Kondaparla,Agarwal, Pooja,Srivastava, Kumkum,Haq,Puri, Sunil K.,Katti
, p. 1148 - 1162 (2016/07/06)
Abstract: A new series of side chain-modified 4-aminoquinolines were synthesized and screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31?μM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain with IC50 values 0.18, 0.22, and 0.17?μM, respectively, as compared to 0.255?μM for chloroquine (CQ). All the compounds displayed good resistance factor between 1.54 and >34.48 as against 51.0 for CQ. All these analogues were found to form strong complex with hematin and inhibited the β-hematin formation in vitro, suggesting that this class of compounds act on a heme polymerization target. Overall results suggest that present series of compounds appear to be promising for further lead optimization to obtain compounds active against drug-resistant parasites. Graphical Abstract: [Figure not available: see fulltext.]
Stereoselective synthesis of southern fragment of hantupeptin A
Srinivas, Avula,Sunitha, Malladi,Rao, Chakunta Govind
, p. 344 - 350 (2016/07/06)
The stereoselective synthesis of the southern fragment (C21-C41) of Hantupeptin A is described. The required stereochemistry of β-hydroxy-α-methyl acid unit was accomplished through the Aldol reaction using Evan's chiral auxiliary followed by the installation of the terminal alkyne with Ohira-Bestmann reagent.
Trichormamides A and B with antiproliferative activity from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339
Luo, Shangwen,Krunic, Aleksej,Kang, Hahk-Soo,Chen, Wei-Lun,Woodard, John L.,Fuchs, James R.,Swanson, Steven M.,Orjala, Jimmy
supporting information, p. 1871 - 1880 (2014/10/16)
Two new cyclic lipopeptides, trichormamides A (1) and B (2), were isolated from the cultured freshwater cyanobacterium Trichormus sp. UIC 10339. The strain was obtained from a sample collected in Raven Lake in Northern Wisconsin. The planar structures of trichormamides A (1) and B (2) were determined using a combination of spectroscopic analyses including HRESIMS and 1D and 2D NMR experiments. The absolute configurations of the amino acid residues were assigned by the advanced Marfey's method after acid hydrolysis. Trichormamide A (1) is a cyclic undecapeptide containing two d-amino acid residues (d-Tyr and d-Leu) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) is a cyclic dodecapeptide characterized by the presence of four nonstandard α-amino acid residues (homoserine, N-methylisoleucine, and two 3-hydroxyleucines) and one β-amino acid residue (β-aminodecanoic acid). Trichormamide B (2) was cytotoxic against MDA-MB-435 and HT-29 cancer cell lines with IC50 values of 0.8 and 1.5 μM, respectively.
Asymmetric total syntheses of marine cyclic depsipeptide halipeptins A-D
Yu, Shouyun,Pan, Xianhua,Ma, Dawei
, p. 6572 - 6584 (2008/09/16)
Halipeptins A-D (1a-d) are a family of natural cyclic depsipeptides isolated from marine sponges. Total syntheses of these four compounds are detailed in this report. The key elements in this synthesis include the elaboration of the polysubstituted decanoic acid parts by two asymmetric aldol reactions, assembly of the N-methyl-δ-hydroxyisoleucine residue by using either aza-Claisen rearrangement or methylation of aspartates as the key steps, and macrocyclization at the polysubstituted decanoic acid alanine site.
Highly N-methylated linear peptides produced by an atypical sponge-derived Acremonium sp.
Boot, Claudia M.,Tenney, Karen,Valeriote, Frederick A.,Crews, Phillip
, p. 83 - 92 (2008/12/21)
RHM1 (1) and RHM2 (2) are highly N-methylated linear octapeptides produced by an atypical strain of Acremonium sp., cultured from a marine sponge collected in Papua New Guinea. The known peptaibiotic efrapeptin G (3) was also isolated from this fungus. The planar structures of 1 and 2 were assigned based on 1D- and 2D-NMR experiments and fragmentation patterns from ESIMS. The absolute configuration of 1 was determined via Marfey's method; the absolute configuration of 2 is proposed to be identical. Efrapeptin G (3) displayed potent cytotoxicity against murine cancer cell lines, while RHM1 (1) and RHM2 (2) showed weak cytotoxicity against murine cancer cell lines; efrapeptin G (3) and RHM1 (1) also demonstrated antibacterial activity.
New cyclic depsipeptide antibiotics, clavariopsins A and B, produced by an aquatic hyphomycetes, Clavariopsis aquatica: 2. Structure analysis
Suzuki,Ojika,Sakagai,Kaida,Fudou,Kameyama
, p. 22 - 28 (2007/10/03)
The structures of new cyclic decadepsipeptides, clavariopsins A and B, were determined to be cyclo[-(R)-2-hydroxyisovaleryl-L-pipecolyl-L-MeVal- L-Val-L-MeAsp-L-Melle-L-Melle-Gly-L-MeVal-L-Tyr(OMe)-] and cyclo[-(R)-2- hydroxyisovaleryl-L-pipecoly-L-Val-L-Val-L-MeAsp-L-Melle-L-Melle-Gly-L- MeVal-L-Tyr(OMe)-], respectively, by spectroscopic analyses, especially using 2D NMR techniques. The absolute stereochemistry was elucidated by the advanced Marfey's method and chiral HPLC analysis.
