638-66-4Relevant academic research and scientific papers
Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis, and biological evaluation against parasitic nematodes
Sugawara, Akihiro,Kubo, Masahiko,Hirose, Tomoyasu,Yahagi, Kyoichi,Tsunoda, Noriaki,Noguchi, Yoshihiko,Nakashima, Takuji,Takahashi, Yoko,Welz, Claudia,Mueller, Dennis,Mertens, Christina,Koebberling, Johannes,ōmura, Satoshi,Sunazuka, Toshiaki
, p. 524 - 538 (2018)
Jietacins, an azoxy antibiotic class of chemicals, were isolated from the culture broth of Streptomyces sp. KP-197. They have a unique structural motif, including a vinyl azoxy group and a long acyclic aliphatic chain, which is usually branched but non-branched in the case of jietacin C. During a drug discovery program, we found that jietacins display potent anthelmintic activity against parasitic nematodes and that jietacin A has a moderate or low acute toxicity (LD50 > 300 mg/kg) and no mutagenic potential in a mini Ames screen. This suggests that jietacins have potential for drug discovery research. In order to create a novel anthelmintic agent, we performed design, synthesis, and biological evaluation of jietacin derivatives against parasitic nematodes. Of these derivatives, we found that a fully synthesized simplified derivative exhibited better anthelmintic activity against three parasitic nematodes than natural jietacins. In addition, it had a better efficacy in vivo through oral administration against a mouse nematode. This indicated that the azoxy motif could prove useful as a template for anthelmintic discovery, possibly creating a class of anthelmintic with novel skeletons, a potential new mode of action, and providing further insight for rational drug design.
Synthesis of novel porphyrin-based lipids and their antibacterial activity
Velidandi, Amarnath,Gadidasu, Kranthi Kumar,Patri, V.Srilakshmi
, p. 1068 - 1073 (2011)
The purpose of this study was to investigate the antibacterial activity of newly developed cationic amphiphilic lipids having porphyrin as head group against two types of gram-positive bacteria and three types of gramnegative bacteria. The antibacterial activity of quantitatively prepared porphyrin-based amphiphilic lipids is evaluated by the disc-diffusion method against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris. These results are compared with the standard antibacterial activity of chloramphenicol. Both lipids showed antibacterial behaviour against gram-positive and gram-negative bacteria. Springer Science+Business Media, LLC 2010.
Hanishenols A-B, novel linear or methyl-branched glycerol enol ethers of the axinellid sponge Acanthella carteri (= Acanthella aurantiaca) from the Hanish Islands, Southern Red Sea
Mancini, Ines,Guella, Graziano,Pietra, Francesco,Amade, Philippe
, p. 2625 - 2628 (1997)
The axinellid sponge Acanthella carteri Dendy, 1889 (= Acanthella aurantiaca Keller, 1889) from the Hanish Islands, Yemen, on EtOH extraction followed by FC and HPLC purification gave the first example of branched glycerol enol ether, hanishenol B (3) alongside a major unbranched analogue, hanishenol A (1). Their structures were elucidated from NMR and MS spectra and through the ozonolysis product of 1, while the absolute configuration was assigned from exciton coupling with the dibenzoate derivative 2.
Lysosomal delivery of a lipophilic gemcitabine prodrug using novel acid-sensitive micelles improved its antitumor activity
Zhu, Saijie,Lansakara-P., Dharmika S. P.,Li, Xinran,Cui, Zhengrong
, p. 966 - 980 (2012)
Stimulus-sensitive micelles are attractive anticancer drug delivery systems. Herein, we reported a novel strategy to engineer acid-sensitive micelles using a amphiphilic material synthesized by directly conjugating the hydrophilic poly(ethylene glycol) (PEG) with a hydrophobic stearic acid derivative (C18) using an acid-sensitive hydrazone bond (PHC). An acid-insensitive PEG-amide-C18 (PAC) compound was also synthesized as a control. 4-(N)-Stearoyl gemcitabine (GemC18), a prodrug of the nucleoside analogue gemcitabine, was loaded into the micelles, and they were found to be significantly more cytotoxic to tumor cells than GemC18 solution, likely due to the lysosomal delivery of GemC18 by micelles. Moreover, GemC18 in the acid-sensitive PHC micelles was more cytotoxic than in the acid-insensitive PAC micelles, which may be attributed to the acid-sensitive release of GemC18 from the PHC micelles in lysosomes. In B16-F10 melanoma-bearing mice, GemC18-loaded PHC or PAC micelles showed stronger antitumor activity than GemC18 or gemcitabine solution, likely because of the prolonged circulation time and increased tumor accumulation of the GemC18 by the micelles. Importantly, the in vivo antitumor activity of GemC18-loaded PHC micelles was significantly stronger than that of the PAC micelles, demonstrating the potential of the novel acid-sensitive micelles as an anticancer drug delivery system.
Balancing the efficacy vs. the toxicity of promiscuous natural products: Paclitaxel-based acid-labile lipophilic prodrugs as promising chemotherapeutics
Chittiboyina, Amar G.,Claudio, Pier Paolo,Haider, Saqlain,McChesney, James D.,Penfornis, Patrice
, (2021/10/19)
TumorSelect is an anticancer technology that combines cytotoxics, nanotechnology, and knowledge of human physiology to develop innovative therapeutic interventions with minimal undesirable side effects commonly observed in conventional chemotherapy. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Several designer prodrugs are incorporated within pseudo-LDL nanoparticles, which carry them to tumor tissues, are taken up, internalized, transformed into active drugs, and inhibit cancer cell proliferation. Highly lipophilic prodrug conjugates of paclitaxel suitable for incorporation into the pseudo-LDL nanoparticles of the TumorSelect delivery vehicle formulation were designed, synthesized, and evaluated in the panel of 24-h NCI-60 human tumor cell line screening to demonstrate the power of such an innovative approach. Taxane prodrugs, viz., ART-207 was synthesized by tethering paclitaxel to lipid moiety with the aid of a racemic solketal as a linker in cost-effective, simple, and straightforward synthetic transformations. In addition to the typical 24-h NCI screening protocol, these compounds were assessed for growth inhibition or killing of ovarian cell lines for 48 and 72h-time intervals and identified the long-lasting effectiveness of these lipophilic prodrugs. All possible, enantiomerically pure isomers of ART-207 were also synthesized, and cytotoxicities were biosimilar to racemic ART-207, suggesting that enantiopurity of linker has a negligible effect on cell proliferation. To substantiate further, ART-207 was evaluated for its in vivo tumor reduction efficacy by studying the xenograft model of ovarian cancer grown in SCID mice. Reduced weight loss (a measure of toxicity) in the ART-207 group was observed, even though it was dosed at 2.5x the paclitaxel equivalent of Abraxane. As a result, our delineated approach is anticipated to improve patient quality of life, patient retention in treatment regimes, post-treatment rapid recovery, and overall patient compliance without compromising the efficacy of the cytotoxic promiscuous natural products.
Ortho -Substituted lipidated Brartemicin derivative shows promising Mincle-mediated adjuvant activity
Foster, Amy J.,Kodar, Kristel,Stocker, Bridget L.,Timmer, Mattie S. M.
supporting information, p. 1095 - 1103 (2020/02/22)
The macrophage inducible C-type lectin (Mincle) is a pathogen recognition receptor (PRR) that is a promising target for the development of Th1-polarising vaccine adjuvants. We recently reported on the synthesis and evaluation of lipidated Brartemicin analogues that showed Mincle agonist activity, with our lead agonist exhibiting potent Th1 adjuvant activity that was greater than that of trehalose dibehenate (TDB). Herein, we report on the efficient synthesis and subsequent biological evaluation of additional lipidated Brartemicin analogues that were designed to determine the structural requirements for optimal Mincle signalling. While all the Brartemicin analogues retained their ability to signal through Mincle and induce a functional response, the o-substituted and m,m-disubstituted derivatives (5a and 5d, respectively) induced a potent inflammatory response when using cells of both murine and human origin, with this response being the greatest observed thus far. As the inflammatory response elicited by 5a was slightly better than that induced by 5d, our findings point to o-substituted Brartemicin analogues as the preferred scaffold for further adjuvant development.
A Simple and Effective Method for Catalytic Oxidation of Alcohols Using the Oxone/Bu4NHSO4 Oxidation System
An, X. Q.,Kang, M.,Ma, H. C.,Yang, Y. X.,Yang, Z. W.,Zeng, W.
, p. 521 - 523 (2020/04/29)
Abstract: A simple and efficient procedure is reported for the oxidation of alcohols tocarbonyl compounds with Oxone (potassium peroxymonosulfate) in the presence oftetrabutylammonium hydrogen sulfate as catalyst with excellent conversion andhigh selectivity using chloroform as solvent at room temperature. The efficiencyof several phase-transfer catalysts in the oxidation of benzyl alcohols andbenzydrol was studied. The proposed catalytic system was also evaluated in theoxidation of alcohols in water at room temperature.
Acridine Photocatalysis: Insights into the Mechanism and Development of a Dual-Catalytic Direct Decarboxylative Conjugate Addition
Arman, Hadi D.,Dang, Hang T.,Haug, Graham C.,Larionov, Oleg V.,Nguyen, Viet D.,Nguyen, Vu T.,Vuong, Ngan T. H.
, p. 11448 - 11457 (2020/11/17)
Conjugate addition is one of the most synthetically useful carbon-carbon bond-forming reactions; however, reactive carbon nucleophiles are typically required to effect the addition. Radical conjugate addition provides an avenue for replacing reactive nucleophiles with convenient radical precursors. Carboxylic acids can serve as simple and stable radical precursors by way of decarboxylation, but activation to reactive esters is typically necessary to facilitate the challenging decarboxylation. Here, we report a direct, dual-catalytic decarboxylative radical conjugate addition of a wide range of carboxylic acids that does not require acid preactivation and is enabled by the visible light-driven acridine photocatalysis interfaced with an efficient copper catalytic cycle. Mechanistic and computational studies provide insights into the roles of the ligands and metal species in the dual-catalytic process and the photocatalytic activity of substituted acridines.
Influence of Some Factors on the Progress of a New Reaction in the Chemistry of Organoaluminum Compounds
Ishmuratov, G. Yu.,Vydrina, V. A.,Yakovleva, M. P.
, p. 1353 - 1358 (2020/10/02)
Abstract: We earlier discovered a new reaction in the chemistry of organoaluminum compounds (OACs), specifically, the formation of O-isobutyl acetals on low-temperature (–70°C) treatment of seven-membered lactones with a double (or more) molar amount of diisobutylaluminum hydride (DIBAH) in methylene chloride. To assess the boundaries for the formation of isobutyl acetals depending on the ring size, we involved in the low-temperature hydride reduction six-, eight-, and thirteen-membered lactones. To determine how the scope of the new reaction depends on the nature of the organoaluminum reagent, we tested triisobutylaluminum (TIBA). To determine how the formation of isobutyl acetals on low-temperature (–70°C) reduction with excess DIBAH in CH2Cl2 depends on whether the starting ester is cyclic or acyclic and, if the former is the case, on the ring size in the ester, we used the acyclic methyl octadecanoate as the starting compound. It was found that the new reaction in the chemistry of AOC with DIBAH as the reducer is characteristic only of seven-membered lactones and atypical of acyclic methyl octadecanoate and ricinoleate (i.e. acids with the carbon chain length more than 6).
BRARTEMICIN ANALOGUES
-
Page/Page column 34; 73, (2019/05/22)
The invention relates to brartemicin analogues of Formula (IV) and their uses. These compounds are potent Mincle agonists and Th1-stimulating vaccine adjuvants.
