2423-10-1Relevant articles and documents
An organocatalyzed Stetter reaction as a bio-inspired tool for the synthesis of nucleic acid-based bioconjugates
Hamoud, Aladin,Barthélémy, Philippe,Desvergnes, Valérie
, p. 1760 - 1769 (2018)
An N-Heterocyclic Carbene (NHC) catalyzed biomimetic Stetter reaction was applied for the first time as a bioconjugation reaction to sensitive nucleoside-type biomolecules to provide original pyrrole linked nucleolipids. A versatile approach allowed the functionalization of thymidine at the three reactive positions (O-5′, O-3′ and N-3) providing a structural diversity oriented synthesis. This strategy was applied to the synthesis of an original glyconucleolipid amphiphile in the hope that the pyrrole aromatic moiety would induce additional self-assembling properties.
Newly synthesized oleylgingerol and oleylshogaol activate TRPV1 ion channels
Morita, Akihito,Iwasaki, Yusaku,Kobata, Kenji,Yokogoshi, Hidehiko,Watanabe, Tatsuo
, p. 2304 - 2307 (2007)
The oleyl moiety in vanilloids is important in activating vanilloid receptor 1 (TRPV1), but there was no ingredient of ginger containing the oleyl moiety in the natural form. We synthesized oleylgingerol and oleylshogaol and then evaluated their potential to activate a rat TRPV1 channel. Oleylgingerol is a stronger TRPV1 agonist than natural gingerols, but oleylshogaol is a weaker agonist than natural shogaols. The difference in structure between oleylgingerol and oleylshogaol is only the hydroxy group at carbon-5. This hydroxy group might have an important role in activating a TRPV1 channel.
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.
OLEIC ACID DERIVATIVES AS TREATMENTS FOR FRIEDREICH ATAXIA AND INHIBITORS OF FERROPTOSIS
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Paragraph 00167, (2021/05/21)
The invention relates to compounds of Formula I or Formula II: to compositions comprising such compounds, and to methods of use thereof for treating neurdegenerative disorders, such as Friedreich ataxia.
COMPOSITIONS FOR TRANSFECTING mRNA INTO A CELL AND THEIR APPLICATIONS
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, (2020/05/29)
The present invention relates to compositions for transfecting a messenger RNA (m RNA) into a cell and their applications. The present invention is directed to a composition for transfecting a mRNA into a cell comprising a mRNA, at least one neutral lipid and a cationic lipid of formula (I), wherein R1 R2, R3, R4 and R5, (CH2)n and A- are as defined in the description. The present invention also relates to uses of said composition and to a method for in vitro transfection of live cells.
Synthesis of (+/-)-Pregabalin and its novel lipophilic β-alkyl-substituted analogues from fatty chains
D'Oca, Caroline Da Ros Montes,Mass, Eduardo Bustos,Ongaratto, Renata Fontes,De Andrade, Arthur Motta,D'Oca, Marcelo G. Montes,Russowsky, Dennis
, p. 13230 - 13239 (2020/08/28)
In this work, were synthesized for the first time a series of new lipophilic β-alkyl substituted GABA derivatives from fatty alkyl chains. The synthesis of these GABA analogues was investigated by two different bicomponent approaches as a key step. The results showed low yields in the path from aliphatic nitroolefins and Meldrum's acid, whereas the Knoevenagel condensation between aliphatic aldehydes and Meldrum's acid afforded fatty alkylidenes in good yields (75-97%). These compounds were subsequently subjected to a conjugate addition reaction with nitromethane, resulting in the fatty Michael adducts (in 87-97% yields) which were in turn submitted to a one pot domino hydrolysis-decarboxylation, leading to the isolation of β-alkyl-substituted γ-nitro acids in good yields (78-92%). Finally, the reduction of the fatty γ-nitro acids allowed for the access to new lipophilic β-alkyl substituted GABA analogues, which were isolated in high yields (90-98%). The new methodology was also applied to the synthesis of antiepileptic drug (+/-)-Pregabalin, which was obtained after four steps in high overall yield. This journal is
Photo-organocatalytic synthesis of acetals from aldehydes
Nikitas, Nikolaos F.,Triandafillidi, Ierasia,Kokotos, Christoforos G.
supporting information, p. 669 - 674 (2019/02/14)
A mild and green photo-organocatalytic protocol for the highly efficient acetalization of aldehydes has been developed. Utilizing thioxanthenone as the photocatalyst and inexpensive household lamps as the light source, a variety of aromatic and aliphatic aldehydes have been converted into acyclic and cyclic acetals in high yields. The reaction mechanism was extensively studied.
Lipidic synthetic alkaloids as SK3 channel modulators. Synthesis and biological evaluation of 2-substituted tetrahydropyridine derivatives with potential anti-metastatic activity
Braire, Julien,Chant?me, Aurélie,Dubreuil, Didier,Félix, Romain,Jaffrès, Paul-Alain,Kouba, Sana,Lebreton, Jacques,Mathé-Allainmat, Monique,Pipelier, Muriel,Potier-Cartereau, Marie,Trebak, Mohamed,Vandier, Christophe,Zhang, Xuexin
, (2019/11/26)
Small Conductance Calcium (Ca2+)-activated potassium (K+) channels (SKCa) are now proved to be involved in many cancer cell behaviors such as proliferation or migration. The SK3 channel isoform was particularly described in breast cancer where it can be associated with the Orai1 Ca2+ channel to form a complex that regulates the Ca2+ homeostasis during tumor development and acts as a potent mediator of bone metastases development in vivo. Until now, very few specific blockers of Orai1 and/or SK3 have been developed as potential anti-metastatic compounds. In this study, we illustrated the synthesis of new families of lipophilic pyridine and tetrahydropyridine derivatives designed as potential modulators of SK3 channel. The toxicity of the newly synthesized compounds and their migration effects were evaluated on the breast cancer cell line MDA-MB-435s. Two molecules (7a and 10c) demonstrated a significant decrease in the SK3 channel-dependent migration as well as the SK3/Orai1-related Ca2+ entry. Current measurements showed that these compounds are more likely SK3-selective. Taken all together these results suggest that such molecules could be considered as promising anti-metastatic drugs in breast cancer.
Proline derivatives incorporating hydrophobic long-chain derived from natural and synthetic fatty acids
Selva, Elisabet,Soto, J. Javier,Nájera, Carmen,Foubelo, Francisco,Sansano, José M.
, p. 1378 - 1386 (2019/02/05)
The α-hydrophobic long chain-α-amino esters are prepared by α-hydroxylation of a series of fatty acid esters [derived from oleic acid (OA), linoleic acid (LA), arachidonic acid (ARA) and docosahexaenoic acid (DHA)] followed by Mitsunobu reaction and hydrazinolysis of the phthalimide. These amino esters are mixed with aldehydes and electrophilic alkenes to give very good chemical yields and diastereoselectivities of prolinate derivatives incorporating a hydrophobic long chain at the α-position. This multicomponent 1,3-dipolar cycloaddition (1,3-DC) takes place at room temperature. The synthesis of the homologue hydrophobic chain of OA is performed by its oxidation to aldehyde/racemic N-tert-butylsulfinyl imine/Neff reaction. Final 1,3-DC with benzaldehyde and N-methylmaleimide affords homologue prolinate derivative in good yield.
Nickel-Catalyzed Selective Reduction of Carboxylic Acids to Aldehydes
Iosub, Andrei V.,Morav?ík, ?tefan,Wallentin, Carl-Johan,Bergman, Joakim
supporting information, p. 7804 - 7808 (2019/10/14)
The direct reduction of carboxylic acids to aldehydes is a fundamental transformation in organic synthesis. The combination of an air-stable Ni precatalyst, dimethyl dicarbonate as an activator, and silane reductant effects this reduction for a wide variety of substrates, including pharmaceutically relevant structures, in good yields and with no overreduction to alcohols. Moreover, this methodology is scalable, allows access to deuterated aldehydes, and is also compatible with one-pot utilization of the aldehyde products.
