638-66-4Relevant articles and documents
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.
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.
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.
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.
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).
