116194-21-9Relevant articles and documents
Antiplasmodial activity of hydroxyethylamine analogs: Synthesis, biological activity and structure activity relationship of plasmepsin inhibitors
Kumar Singh, Amit,Rajendran, Vinoth,Singh, Snigdha,Kumar, Prashant,Kumar, Yogesh,Singh, Archana,Miller, Whelton,Potemkin, Vladimir,Poonam,Grishina, Maria,Gupta, Nikesh,Kempaiah, Prakasha,Durvasula, Ravi,Singh, Brajendra K.,Dunn, Ben M.,Rathi, Brijesh
, p. 3837 - 3844 (2018)
Malaria, particularly in endemic countries remains a threat to the human health and is the leading the cause of mortality in the tropical and sub-tropical areas. Herein, we explored new C2 symmetric hydroxyethylamine analogs as the potential inhibitors of Plasmodium falciparum (P. falciparum; 3D7) in in-vitro cultures. All the listed compounds were also evaluated against crucial drug targets, plasmepsin II (Plm II) and IV (Plm IV), enzymes found in the digestive vacuole of the P. falciparum. Analog 10f showed inhibitory activities against both the enzymes Plm II and Plm IV (Ki, 1.93 ± 0.29 μM for Plm II; Ki, 1.99 ± 0.05 μM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (Ki, 0.84 ± 0.08 μM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC50, 2.27 ± 0.95 μM for 10f; IC50, 3.11 ± 0.65 μM for 10g) displayed marked killing effect. A significant growth inhibition of the P. falciparum was displayed by analog 12c with IC50 value of 1.35 ± 0.85 μM, however, it did not show inhibitory activity against either Plms. The hemolytic assay suggested that the active compounds selectively inhibit the growth of the parasite. Further, potent analogs (10f and 12c) were evaluated for their cytotoxicity towards mammalian HepG2 and vero cells. The selectivity index (SI) values were noticed greater than 10 for both the analogs that suggested their poor toxicity. The present study indicates these analogs as putative lead structures and could serve as crucial for the development of new drug molecules.
Total synthesis of the azolemycins
Anderson, Zoe J.,Fox, David J.
, p. 1450 - 1454 (2016)
The first total syntheses of newly isolated polyazole natural products azolemycins A-D, along with the synthesis of the tetra-oxazole non-natural analogue, are described.
1,3-Diastereocontrol with Bromoallenes. Synthesis of Enantiomerically Pure β-Branched α-Amino Acids
D'Aniello, Fabiana,Mann, Andre,Taddei, Maurizio,Wermuth, Camille-Georges
, p. 7775 - 7778 (1994)
Bromoallenes 3a and 3b derived from (D)-Serine undergo SN2' alkylation with organo copper reagents to give alkynyl amino alcohol derivatives.These compounds can be further transformed into branched enantiomerically enriched α-amino acids as, for example (L)-Isoleucine and (L)-Alloisoleucine.
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.]
Lipopeptides from the tropical marine cyanobacterium symploca sp.
Mevers, Emily,Haeckl, F. P. Jake,Boudreau, Paul D.,Byrum, Tara,Dorrestein, Pieter C.,Valeriote, Frederick A.,Gerwick, William H.
, p. 969 - 975 (2014/05/20)
A collection of the tropical marine cyanobacterium Symploca sp., collected near Kimbe Bay, Papua New Guinea, previously yielded several new metabolites including kimbeamides A-C, kimbelactone A, and tasihalide C. Investigations into a more polar cytotoxic fraction yielded three new lipopeptides, tasiamides C-E (1-3). The planar structures were deduced by 2D NMR spectroscopy and tandem mass spectrometry, and their absolute configurations were determined by a combination of Marfeys and chiral-phase GC-MS analysis. These new metabolites are similar to several previously isolated compounds, including tasiamide (4), grassystatins (5, 6), and symplocin A, all of which were isolated from similar filamentous marine cyanobacteria.
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.
Discovery of a pair of diastereomers as potent HDACs inhibitors: Determination of absolute configuration, biological activity comparison and computational study
Zhang, Yingjie,Inks, Elizabeth S.,Zhu, Mengyuan,Chou, C. James,Fang, Hao,Li, Minyong,Shen, Yuemao,Yi, Fan,Xu, Wenfang
, p. 21106 - 21109 (2013/11/06)
Histone deacetylase inhibitors (HDACi) are still the focus of epigenetic modulator development due to their effective intervention in many pathological processes. In our previous research, a potent HDACi was designed, synthesized and validated as a promising antitumor candidate named ZYJ-34c. Enlarged scale synthesis of ZYJ-34c for further detailed research was hindered by the occurrence of a by-product, which was identified as an isomer of ZYJ-34c by HRMS and 1H NMR. Subsequent synthesis route modification and optimization revealed that these two isomers were a pair of epimers and their absolute configurations could be directly determined by our optimized synthesis routes, through which each optically pure epimer could be stereoselectively synthesized, respectively. Based on these results, we concluded that our previously reported absolute configuration of ZYJ-34c was incorrect. It is worth noting that the epimer of ZYJ-34c exhibited more potent HDACs inhibition and both in vitro and in vivo antitumor activities, and moreover, their different HDACs inhibitory activities could be rationalized by computational simulations of their binding modes in HDAC2. The Royal Society of Chemistry 2013.
Design, synthesis, and biological activity of thiazole derivatives as novel influenza neuraminidase inhibitors
Liu,Zhang, Lei,Gong, Jianzhi,Fang, Hao,Liu, Ailin,Du, Guanhua,Xu, Wenfang
scheme or table, p. 506 - 513 (2012/06/01)
A series of novel influenza neuraminidase (NA) inhibitors based on thiazole core were synthesized and evaluated for their ability to inhibit NA of influenza A virus (H3N2). All compounds were synthesized in good yields starting from commercially available 2-amino-4-thiazole-acetic ester using a suitable synthetic strategy. These compounds showed moderate inhibitory activity against influenza A NA. The most potent compound of this series is compound 4d (IC50=3.43 μM), which is about 20-fold less potent than oseltamivir, and could be used to design novel influenza NA inhibitors that exhibit increased activity based on thiazole ring.
Preparation and biological evaluation of key fragments and open analogs of scleritodermin A
Sellanes, Diver,Campot, Francisco,Nú?ez, Ivana,Lin, Gerardo,Espósito, Pablo,Dematteis, Sylvia,Salda?a, Jenny,Domílnguez, Laura,Manta, Eduardo,Serra, Gloria
scheme or table, p. 5384 - 5395 (2010/08/19)
The synthesis of key fragments of scleritodermin A, their assembly, and their biological evaluation as cytotoxic and anthelmintic were performed.Highlights of the synthetic route include formation of the a-ketoamide linkage and use of stereocontrolled reactions.Open analogs of this natural product were obtained using a convergent strategy.
Toward the total synthesis of Scleritodermin A: preparation of the C1-N15 fragment
Sellanes, Diver,Manta, Eduardo,Serra, Gloria
, p. 1827 - 1830 (2008/02/05)
The synthesis of the C1-N15 fragment of the marine natural product Scleritodermin A has been accomplished through a short and stereocontrolled sequence. Highlights of this route include the synthesis of the novel ACT fragment and the formation of the α-keto amide linkage by the use of a highly activated α,β-ketonitrile.
