- Caldoramide, a Modified Pentapeptide from the Marine Cyanobacterium Caldora penicillata
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The isolation, structure determination, and biological activities of a new linear pentapeptide, caldoramide (5), from the marine cyanobacterium Caldora penicillata from Florida are described. Caldoramide (5) has structural similarities to belamide A (4), dolastatin 10 (1), and dolastatin 15 (2). We profiled caldoramide against parental HCT116 colorectal cancer cells and isogenic cells lacking oncogenic KRAS or hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α). Caldoramide (5) showed differential cytotoxicity for cells containing both oncogenic KRAS and HIF over the corresponding knockout cells. LCMS dereplication indicated the presence of caldoramide (5) in a subset of C. penicillata samples.
- Gunasekera, Sarath P.,Imperial, Lorelie,Garst, Christiana,Ratnayake, Ranjala,Dang, Long H.,Paul, Valerie J.,Luesch, Hendrik
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- Genomics-driven discovery of a new cyclodepsipeptide from the guanophilic fungusAmphichorda guana
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Two potential non-ribosomal peptide synthetases (NRPSs) were identified in the genome of a guanophilic fungusAmphichorda guanaby bioinformatics analysis and gene knockout experiments. Liquid chromatography coupled with mass spectrometry (LC-MS) guided isolation led to the discovery of a new cyclodepsipeptide isaridin H (1) and seven known analogs, desmethylisaridin E (2), isaridin E (3), isariin A (4), iso-isariin B (5), iso-isariin D (6), isariin E (7), and nodupetide (8). The absolute configuration of isaridin H (1) was achieved by Marfey's method. Isaridin H (1) showed significant antifungal activity againstBotrytis cinereaandAlternaria solani.
- Liang, Min,Lyu, Hai-Ning,Ma, Zi-Ying,Li, Er-Wei,Cai, Lei,Yin, Wen-Bing
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p. 1960 - 1964
(2021/03/16)
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- Komesuamide and odopenicillatamide, two linear lipopeptides from the marine cyanobacterium Caldora penicillata
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The linear lipopeptides komesuamide (1) and odopenicillatamide (2) were isolated from Caldora penicillata a marine cyanobacterium collected in Okinawa. The structures of these compounds were established by spectroscopic analyses, and the absolute configurations were determined by HPLC analyses of the acid hydrolysates. Both compounds showed glucose uptake activity at 40 μM in cultured L6 myotubes.
- Ozaki, Kaori,Jinno, Atsuhide,Natsume, Noriyuki,Sumimoto, Shimpei,Iwasaki, Arihiro,Suenaga, Kiyotake,Teruya, Toshiaki
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- Iheyamides A-C, Antitrypanosomal Linear Peptides Isolated from a Marine Dapis sp. Cyanobacterium
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Iheyamides A (1), B (2), and C (3), new linear peptides, were isolated from a marine Dapis sp. cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Iheyamide A (1) showed moderate antitrypanosomal activities against Trypanosoma brucei rhodesiense and Trypanosoma brucei brucei (IC50 = 1.5 μM), but the other two analogues, iheyamides B (2) and C (3), did not (IC50 > 20 μM, respectively). The structure-activity relationship clarified that an isopropyl-O-Me-pyrrolinone moiety was necessary for the antitrypanosomal activity. Furthermore, the cytotoxicity of 1 against normal human cells, WI-38, was 10 times weaker than its antitrypanosomal activity (IC50 = 18 μM).
- Kurisawa, Naoaki,Iwasaki, Arihiro,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
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p. 1684 - 1690
(2020/06/08)
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- Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia
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Heisteria parvifolia Sm. is prescribed in traditional medecine against numerous diseases in C?te d'Ivoire. Due to the shortcoming in scientifical knowledge of use of this species, our investigations revealed five undescribed cyclopeptide alkaloids added to one known derivative namely anorldianine. These compounds were elucidated by 1D and 2D-NMR experiments and comparison with literature data, and confirmed by HR-ESI-MS. Cytotoxic activity evaluation of these compounds against the chronic myeloid leukemia (K565) cell line exhibited an antiproliferative activity with cell growth inhibition from 13% to 46%.
- Bitchi, Michel Boni,Magid, Abdulmagid Alabdul,Kabran, Faustin Aka,Yao-Kouassi, Philomène Akoua,Harakat, Dominique,Morjani, Hamid,Tonzibo, Félix Zanahi,Voutquenne-Nazabadioko, Laurence
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- Dudawalamides A-D, Antiparasitic Cyclic Depsipeptides from the Marine Cyanobacterium Moorea producens
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A family of 2,2-dimethyl-3-hydroxy-7-octynoic acid (Dhoya)-containing cyclic depsipeptides, named dudawalamides A-D (1-4), was isolated from a Papua New Guinean field collection of the cyanobacterium Moorea producens using bioassay-guided and spectroscopic approaches. The planar structures of dudawalamides A-D were determined by a combination of 1D and 2D NMR experiments and MS analysis, whereas the absolute configurations were determined by X-ray crystallography, modified Marfey's analysis, chiral-phase GCMS, and chiral-phase HPLC. Dudawalamides A-D possess a broad spectrum of antiparasitic activity with minimal mammalian cell cytotoxicity. Comparative analysis of the Dhoya-containing class of lipopeptides reveals intriguing structure-activity relationship features of these NRPS-PKS-derived metabolites and their derivatives.
- Almaliti, Jehad,Malloy, Karla L.,Glukhov, Evgenia,Spadafora, Carmenza,Gutiérrez, Marcelino,Gerwick, William H.
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p. 1827 - 1836
(2017/06/28)
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- Odobromoamide, a terminal alkynyl bromide-containing cyclodepsipeptide from the marine cyanobacterium okeania sp.
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The bioassay-guided fractionation of the Okinawan marine cyanobacterium Okeania sp. led to the isolation of the novel cyclodepsipeptide odobromoamide (1). The gross structure of 1 was determined by spectroscopic analyses, and its absolute stereochemistry was determined using a variety of different methods, including chemical derivatization and degradation followed by HPLC analysis. In addition, odobromoamide (1) exhibited broad-spectrum cytotoxicity against a human cancer cell line panel.
- Sueyoshi, Kosuke,Kudo, Takafumi,Yamano, Aki,Sumimoto, Shimpei,Iwasaki, Arihiro,Suenaga, Kiyotake,Teruya, Toshiaki
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p. 436 - 440
(2017/06/14)
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- Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium
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Biseokeaniamides A, B, and C (1-3), structurally novel sterol O-acyltransferase (SOAT) inhibitors, were isolated from an Okeania sp. marine cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Biseokeaniamide B (2) exhibited moderate cytotoxicity against human HeLa cancer cells, and compounds 1-3 inhibited both SOAT1 and SOAT2, not only at an enzyme level but also at a cellular level. Biseokeaniamides (1-3) are the first linear lipopeptides that have been shown to exhibit SOAT-inhibitory activity.
- Iwasaki, Arihiro,Tadenuma, Takato,Sumimoto, Shimpei,Ohshiro, Taichi,Ozaki, Kaori,Kobayashi, Keisuke,Teruya, Toshiaki,Tomoda, Hiroshi,Suenaga, Kiyotake
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p. 1161 - 1166
(2017/05/05)
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- Urumamide, a novel chymotrypsin inhibitor with a β-amino acid from a marine cyanobacterium Okeania sp.
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Urumamide, a novel cyclic depsipeptide that contains a β-amino acid, was isolated from a marine cyanobacterium Okeania sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on Marfey's analyses and chiral HPLC analyses of hydrolysis products. Biologically, urumamide inhibited the growth of human cancer cells. In addition, urumamide inhibited chymotrypsin.
- Kanamori, Yuki,Iwasaki, Arihiro,Sumimoto, Shinpei,Suenaga, Kiyotake
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supporting information
p. 4213 - 4216
(2016/08/25)
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- Pembamide, a N-methylated linear peptide from a sponge Cribrochalina sp.
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A new highly N-methylated linear peptide, pembamide (1), has been isolated from the marine sponge Cribrochalina sp. (family Niphatidae) collected off the coast of Pemba (Tanzania). The planar structure of 1 was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 was determined by application of the Advanced Marfey's method. Compound 1 displayed significant cytotoxicity against three human tumor cell lines with GI50values in the micromolar range.
- Urda, Carlos,Pérez, Marta,Rodríguez, Jaime,Jiménez, Carlos,Cuevas, Carmen,Fernández, Rogelio
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supporting information
p. 3239 - 3242
(2016/07/11)
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- Jahanyne, an apoptosis-inducing lipopeptide from the marine cyanobacterium lyngbya sp.
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An acetylene-containing lipopeptide, jahanyne, was isolated from the marine cyanobacterium Lyngbya sp. Its gross structure was established by spectroscopic analyses, and the absolute configuration was clarified based on a combination of chiral HPLC analyses, spectroscopic analyses, and derivatization reactions. Jahanyne significantly inhibited the growth of human cancer cells and induced apoptosis in HeLa cells.
- Iwasaki, Arihiro,Ohno, Osamu,Sumimoto, Shinpei,Ogawa, Hidetoshi,Nguyen, Kim Anh,Suenaga, Kiyotake
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supporting information
p. 652 - 655
(2015/03/05)
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- Anti-respiratory syncytial virus prenylated dihydroquinolone derivatives from the gorgonian-derived fungus aspergillus sp. XS-20090B15
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Two new prenylated dihydroquinolone derivatives, 22-O-(N-Me-l-valyl)aflaquinolone B (1) and 22-O-(N-Me-l-valyl)-21-epi-aflaquinolone B (2), and two known analogues, aflaquinolones A (3) and D (or a diastereomer of D, 4), were isolated from the mycelia of a gorgonian-derived Aspergillus sp. fungus. The structures of the new compounds were elucidated by spectroscopic methods, ECD spectra, Marfey's method, and chemical conversion. Compounds 1 and 2 display an unusual esterification of N-Me-l-Val to the side-chain prenyl group. Compound 2 exhibited outstanding anti-RSV activity with an IC50 value of 42 nM, approximately 500-fold stronger than that of the positive control ribavirin (IC50 = 20 μM), and showed a comparatively higher therapeutic ratio (TC50/IC50 = 520).
- Chen, Min,Shao, Chang-Lun,Meng, Hong,She, Zhi-Gang,Wang, Chang-Yun
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p. 2720 - 2724
(2015/02/02)
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- Ohmyungsamycins A and B: Cytotoxic and antimicrobial cyclic peptides produced by Streptomyces sp. from a volcanic island
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Ohmyungsamycins A and B (1 and 2), which are new cyclic peptides, were isolated from a marine bacterial strain belonging to the Streptomyces genus collected from a sand beach on Jeju, a volcanic island in the Republic of Korea. Based on the interpretation of the NMR, UV, and IR spectroscopic and MS data, the planar structures of 1 and 2 were elucidated as cyclic depsipeptides bearing unusual amino acid units, including N-methyl-4-methoxytrytophan, β-hydroxyphenylalanine, and N,N-dimethylvaline. The absolute configurations of the α-carbons of the amino acid residues were determined using the advanced Marfey's method. The configurations of the additional stereogenic centers at the β-carbons of the threonine, N-methylthreonine, and β-hydroxyphenylalanine units were assigned by GITC (2,3,4,6-tetra-O-acetyl- β-d-glucopyranosyl isothiocyanate) derivatization and the modified Mosher's method. We have developed a new method utilizing PGME (phenylglycine methyl ester) derivatization coupled with chromatographic analysis to determine the absolute configuration of N,N-dimethylvaline. Our first successful establishment of the absolute configuration of N,N-dimethylvaline using PGME will provide a general and convenient analytical method for determining the absolute configurations of amino acids with fully substituted amine groups. Ohmyungsamycins A and B showed significant inhibitory activities against diverse cancer cells as well as antibacterial effects.
- Um, Soohyun,Choi, Tae Joon,Kim, Heegyu,Kim, Byung Yong,Kim, Seong-Hwan,Lee, Sang Kook,Oh, Ki-Bong,Shin, Jongheon,Oh, Dong-Chan
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p. 12321 - 12329
(2014/01/17)
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- Two new 14-membered cyclopeptide alkaloids from Zizyphus xylopyra
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The phytochemical investigation of the bark of Zizyphus xylopyra resulted in the isolation of two new 14-membered ring cyclopeptide alkaloids, xylopyrine-G and xylopyrine H. Their structures have been established by chemical and spectral evidences.
- Pandey, Manoj B.,Singh, Sarita,Malhotra, Meenakshi,Pandey, Vidya B.,Singh, Tryambak D.
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experimental part
p. 836 - 841
(2012/10/07)
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- Cyclohexadepsipeptides from Acremonium sp. BCC 28424
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Six new cyclohexadepsipeptides, beauvenniatins A-E (1-5), and beauvericin J (6), together with the known beauvericin (7) and enniatin B (8), were isolated from the fungus Acremonium sp. BCC 28424. The productions of minor derivatives 3-6, possessing an N-
- Isaka, Masahiko,Yangchum, Arunrat,Sappan, Malipan,Suvannakad, Rapheephat,Srikitikulchai, Prasert
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experimental part
p. 7929 - 7935
(2011/11/07)
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- Cytotoxic halogenated macrolides and modified peptides from the apratoxin-producing marine cyanobacterium Lyngbya bouillonii from Guam
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Collections of the marine cyanobacterium Lyngbya bouillonii from shallow patch reefs in Apra Harbor, Guam, afforded three hitherto undescribed analogues of the glycosidic macrolide lyngbyaloside, namely, 2-epi-lyngbyaloside (1) and the regioisomeric 18E- and 18Z-lyngbyalosides C (2 and 3). Concurrently we discovered two new analogues of the cytoskeletal actin-disrupting lyngbyabellins, 27-deoxylyngbyabellin A (4) and lyngbyabellin J (5), a novel macrolide of the laingolide family, laingolide B (6), and a linear modified peptide, lyngbyapeptin D (7), along with known lyngbyabellins A and B, lyngbyapeptin A, and lyngbyaloside. The structures of 1-7 were elucidated by a combination of NMR spectroscopic and mass spectrometric analysis. Compounds 1-6 were either brominated (1-3) or chlorinated (4-6), consistent with halogenation being a hallmark of many marine natural products. All extracts derived from these L. bouillonii collections were highly cytotoxic due to the presence of apratoxin A or apratoxin C. Compounds 1-5 showed weak to moderate cytotoxicity to HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells.
- Matthew, Susan,Salvador, Lilibeth A.,Schupp, Peter J.,Paul, Valerie J.,Luesch, Hendrik
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experimental part
p. 1544 - 1552
(2010/12/25)
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- Cyclic tripeptides from the halotolerant fungus Aspergillus sclerotiorum PT06-1
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Eleven new aspochracin-type cyclic tripeptides, sclerotiotides A-K (1-11), together with three known compounds, JBIR-15 (12), aspochracin (13), and penicillic acid, were isolated from the ethyl acetate extract of the fermentation broth of the halotolerant Aspergillus sclerotiorum PT06-1 in a hypersaline nutrient-rich medium. Their structures were elucidated by spectroscopic analysis and chemical methods. Chemical transformations of 12 and 13 proved that sclerotiotides D-K (4-11) were artifacts probably formed during the fermentation or subsequent isolation steps. All 13 cyclic tripeptides have been evaluated for their antimicrobial and cytotoxic effects. Only sclerotiotides A (1), B (2), F (6), and I (9) and JBIR-15 (12) showed selective antifungal activity against Candida albicans with MIC values of 7.5, 3.8, 30, 6.7, and 30 μM, respectively.
- Zheng, Jinkai,Xu, Zhihong,Wang, Yi,Hong, Kui,Liu, Peipei,Zhu, Weiming
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experimental part
p. 1133 - 1137
(2010/09/10)
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- Evolved diversification of a modular natural product pathway: Apratoxins F and G, two cytotoxic cyclic depsipeptides from a palmyra collection of Lyngbya bouillonii
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A collection of Lyngbya bouillonii from Palmyra Atoll in the Central Pacific, a site several thousand kilometers distant from all previous collections of this chemically prolific species of cyanobacterium, was found to contain two new cancer cell cytotoxins of the apratoxin family. The structures of the new compounds, apratoxins F and G, were determined by 1D and 2D NMR techniques in combination with mass spectrometric methods. Stereochemistry was explored by using chromatographic analyses of the hydrolytically released fragments in combination with NMR and optical rotation comparisons with known members of the apratoxin family. Apratoxins F and G add fresh insights into the SAR of this family because they incorporate an N-methyl alanine residue at a position where all prior apratoxins have possessed a proline unit, yet they retain high potency as cytotoxins to H-460 cancer cells with IC50 values of 2 and 14 nM, respectively. Additional assays using zone inhibition of cancer cells and clonogenic cells give a comparison of the activities of apratoxin F to apratoxin A. Additionally, the clonogenic studies in combination with maximum tolerated dose (MTD) studies provided insights as to dosing schedules that should be used for in vivo studies, and preliminary in vivo evaluation validated the predicted in vivo efficacy for apratoxin A. These new apratoxins are illustrative of a mechanism (the modification of an NRPS adenylation domain specificity pocket) for evolving a biosynthetic pathway so as to diversify the suite of expressed secondary metabolites.
- Tidgewell, Kevin,Engene, Niclas,Byrum, Tara,Media, Joseph,Doi, Takayuki,Valeriote, Fred A.,Gerwick, William H.
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experimental part
p. 1458 - 1466
(2011/05/02)
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- Grassypeptolides A-C, cytotoxic bis-thiazoline containing marine cyclodepsipeptides
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Grassypeptolides A-C (1-3), a group of closely related bis-thiazoline containing cyclic depsipeptides, have been isolated from extracts of the marine cyanobacterium Lyngbya confervoides. Although structural differences between the analogues are minimal, comparison of the in vitro cytotoxicity of the series revealed a structure-activity relationship. When the ethyl substituent of 1 is changed to a methyl substituent in 2, activity is only slightly reduced (3-4-fold), whereas inversion of the Phe unit flanking the bis-thiazoline moiety results in 16-23-fold greater potency. We show that both 1 and 3 cause G1 phase cell cycle arrest at lower concentrations, followed at higher concentrations by G2/M phase arrest, and that these compounds bind Cu2+ and Zn 2+. The three-dimensional structure of 2 was determined by MS, NMR, and X-ray crystallography, and the structure of 3 was established by MS, NMR, and chemical degradation. The structure of 3 was explored by in silico molecular modeling, revealing subtle differences in overall conformation between 1 and 3. Attempts to interconvert 1 and 3 with base were unsuccessful, but enzymatic conversion may be possible and could be a novel form of activation for chemical defense.
- Kwan, Jason C.,Ratnayake, Ranjala,Abboud, Khalil A.,Paul, Valerie J.,Luesch, Hendrik
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experimental part
p. 8012 - 8023
(2011/03/20)
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- Halogenated fatty acid amides and cyclic depsipeptides from an eastern Caribbean collection of the cyanobacterium Lyngbya majuscula
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A lipophilic extract of an eastern Caribbean collection of Lyngbya majuscula yielded two new halogenated fatty acid amides, grenadamides B (1) and C (2), and two new depsipeptides, itralamides A (3) and B (4), along with the known compounds hectochlorin a
- Jimenez, Jorge I.,Vansach, Tifanie,Yoshida, Wesley Y.,Sakamoto, Bryan,Poerzgen, Peter,Horgen, F. David
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supporting information; experimental part
p. 1573 - 1578
(2010/03/31)
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- Viridamides A and B, lipodepsipeptides with antiprotozoal activity from the marine cyanobacterium Oscillatoria nigro-viridis
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Parallel chemical and phylogenetic investigation of a marine cyanobacterium from Panama led to the isolation of two new PKS-NRPS-derived compounds, viridamides A and B. Their structures were determined by NMR and mass spectroscopic methods, and the absolute configurations assigned by Marfey's method and chiral HPLC analysis. In addition to six standard, N-methylated amino and hydroxy acids, these metabolites contained the structurally novel 5-methoxydec-9-ynoic acid moiety and an unusual proline methyl ester terminus. Morphologically, this cyanobacterium was identified as Oscillatoria nigro-viridis, and its 16S rDNA sequence is reported here for the first time. Phylogenetic analysis of these sequence data has identified O. nigro-viridis strain OSC3L to be closely related to two other marine cyanobacterial genera, Trichodesmium and Blennothrix. Viridamide A showed antitrypanosomal activity with an IC50 of 1.1 μM and antileishmanial activity with an IC50 of 1.5 μM.
- Simmons, T. Luke,Engene, Niclas,Urena, Luis David,Romero, Luz I.,Ortega-Barria, Eduardo,Gerwick, Lena,Gerwick, William H.
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experimental part
p. 1544 - 1550
(2009/09/06)
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- MAJUSCULAMIDE D AND DEOXYMAJUSCULAMIDE D, TWO CYTOTOXINS FROM LYNGBYA MAJUSCULA
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Majusculamide D and deoxymajusculamide D are cytotoxic lipopentapeptides that are minor constituents of a deep-water variety of the marine blue-green alga Lyngbya majuscula from Enewetak. Key Word Index - Lyngbya majuscula; Oscillatoriaceae; blue-green alga; lipopentapeptides; cytotoxins.
- Moore, Richard E.,Entzeroth, Michael
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p. 3101 - 3104
(2007/10/02)
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