6302-65-4Relevant academic research and scientific papers
A LecA ligand identified from a galactoside-conjugate array inhibits host cell invasion by pseudomonas aeruginosa
Novoa, Alexandre,Eierhoff, Thorsten,Topin, Jeremie,Varrot, Annabelle,Barluenga, Sofia,Imberty, Anne,Roemer, Winfried,Winssinger, Nicolas
, p. 8885 - 8889 (2014)
Lectin LecA is a virulence factor of Pseudomonas aeruginosa involved in lung injury, mortality, and cellular invasion. Ligands competing with human glycoconjugates for LecA binding are thus promising candidates to counteract P. aeruginosa infections. We have identified a novel divalent ligand from a focused galactoside(Gal)-conjugate array which binds to LecA with very high affinity (Kd=82 nM). Crystal structures of LecA complexed with the ligand together with modeling studies confirmed its ability to chelate two binding sites of LecA. The ligand lowers cellular invasiveness of P. aeruginosa up to 90% when applied in the range of 0.05-5 μM. Hence, this ligand might lead to the development of drugs against P. aeruginosa infection.
Novel nicotinoid structures for covalent modification of wood: An environmentally friendly way for its protection against insects
Acker, Sophie,Kaufmann, Dieter E.,Namyslo, Jan C.,Plarre, Rudy,S?ftje, Martin
, p. 15726 - 15733 (2020/05/13)
Timber is constantly exposed to environmental influences under outdoor conditions which limits its lifetime and usability. In order to counteract the damaging processes caused by insects, we have developed a novel and more environmentally friendly method to protect wood materials via covalent modification by organic insecticides. Starting with an important class of synthetic insecticides which are derived from the natural insecticide nicotine, various new carboxylic acid derivatives of imidacloprid were made accessible. These activated neonicotinoids were utilized for the chemical modification of wood hydroxy groups. In contrast to conventional wood preservation methods in which biocides are only physically bound to the surface for a limited time, the covalent fixation of the preservative guarantees a permanent effect against wood pests, demonstrated in standardized biological tests. Additionally, the environmental interaction caused by non-bound neonicotinoids is significantly reduced, since both, a smaller application rate is required and leaching of the active ingredient is prevented. By minimizing the pest infestation, the lifetime of the material increases while preserving the natural appearance of the material.
Electrochemically Catalyzed Newman-Kwart Rearrangement: Mechanism, Structure-Reactivity Relationship, and Parallels to Photoredox Catalysis
Roesel, Arend F.,Ugandi, Mihkel,Huyen, Nguyen Thi Thu,Májek, Michal,Broese, Timo,Roemelt, Michael,Francke, Robert
, p. 8029 - 8044 (2020/07/25)
The facilitation of redox-neutral reactions by electrochemical injection of holes and electrons, also known as "electrochemical catalysis", is a little explored approach that has the potential to expand the scope of electrosynthesis immensely. To systematically improve existing protocols and to pave the way toward new developments, a better understanding of the underlying principles is crucial. In this context, we have studied the Newman-Kwart rearrangement of O-arylthiocarbamates to the corresponding S-aryl derivatives, the key step in the synthesis of thiophenols from the corresponding phenols. This transformation is a particularly useful example because the conventional method requires temperatures up to 300 °C, whereas electrochemical catalysis facilitates the reaction at room temperature. A combined experimental-quantum chemical approach revealed several reaction channels and rendered an explanation for the relationship between the structure and reactivity. Furthermore, it is shown how rapid cyclic voltammetry measurements can serve as a tool to predict the feasibility for specific substrates. The study also revealed distinct parallels to photoredox-catalyzed reactions, in which back-electron transfer and chain propagation are competing pathways.
Expanding the SAR of Nontoxic Antiplasmodial Indolyl-3-ethanone Ethers and Thioethers
Lunga, Mayibongwe J.,Chisango, Ruramai L.,Weyers, Carli,Isaacs, Michelle,Taylor, Dale,Edkins, Adrienne L.,Khanye, Setshaba D.,Hoppe, Heinrich C.,Veale, Clinton G. L.
, p. 1353 - 1362 (2018/07/13)
Despite major strides in reducing Plasmodium falciparum infections, this parasite still accounts for roughly half a million annual deaths. This problem is compounded by the decreased efficacy of artemisinin combination therapies. Therefore, the development and optimisation of novel antimalarial chemotypes is critical. In this study, we describe our strategic approach to optimise a class of previously reported antimalarials, resulting in the discovery of 1-(5-chloro-1H-indol-3-yl)-2-[(4-cyanophenyl)thio]ethanone (13) and 1-(5-chloro-1H-indol-3-yl)-2-[(4-nitrophenyl)thio]ethanone (14), whose activity was equipotent to that of chloroquine against the P. falciparum 3D7 strain. Furthermore, these compounds were found to be nontoxic to HeLa cells as well as being non-haemolytic to uninfected red blood cells. Intriguingly, several of our most promising compounds were found to be less active against the isogenic NF54 strain, highlighting possible issues with long-term dependability of malarial strains. Finally compound 14 displayed similar activity against both the NF54 and K1 strains, suggesting that it inhibits a pathway that is uncompromised by K1 resistance.
Synthesis and cytotoxicity studies of novel NHC?-gold(I) complexes derived from lepidiline A
Curran, Danielle,Dada, Oyinlola,Müller-Bunz, Helge,Rothemund, Matthias,Sánchez-Sanz, Goar,Schobert, Rainer,Zhu, Xiangming,Tacke, Matthias
, (2018/09/26)
Ten novel N-heterocyclic carbene gold(I) complexes derived from lepidiline A (1,3-dibenzyl-4,5-dimethylimidazolium chloride) are reported here with full characterisation and biological testing. (1,3-Dibenzyl-4,5-diphenylimidazol-2-ylidene)gold(I) chloride (NHC?-AuCl) (1) was modified by substituting the chloride for the following: cyanide (2), dithiocarbamates (3-5), p-mercaptobenzoate derivatives (12-14) and N-acetyl-L-cysteine derivatives (15-17). All complexes were synthesised in good yields of 57-78%. Complexes 2, 12, 13, and 14 were further characterised by X-ray crystallography. Initial evaluation of the biological activity was conducted on all ten complexes against the multidrug resistant MCF-7topo breast cancer, HCT-116wt, and p53 knockout mutant HCT-116-/- colon carcinoma cell lines. Across the three cell lines tested, mainly single-digit micromolar IC50 values were observed. Nanomolar activity was exhibited on the MCF-7topo cell line with 3 displaying an IC50 of 0.28 μM ± 0.03 μM. Complexes incorporating a Au-S bond resulted in higher cytotoxic activity when compared to complexes 1 and 2. Theoretical calculations, carried out at the MN15/6-311++G(2df,p) computational level, show that NHC? is the more favourable ligand for Au(I)-Cl when compared to PPh3.
Lithium-Catalyzed Thiol Alkylation with Tertiary and Secondary Alcohols: Synthesis of 3-Sulfanyl-Oxetanes as Bioisosteres
Croft, Rosemary A.,Mousseau, James J.,Choi, Chulho,Bull, James A.
supporting information, p. 818 - 821 (2017/12/26)
3-Sulfanyl-oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li catalyst enables chemoselective C?OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various π-activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts.
Radical Difluoromethylation of Thiols with (Difluoromethyl)triphenylphosphonium Bromide
Heine, Niklas B.,Studer, Armido
supporting information, p. 4150 - 4153 (2017/08/14)
A method for facile difluoromethylation of various thiols using (difluoromethyl)triphenylphosphonium bromide under mild reaction conditions is presented. The transformation proceeds in the absence of any transition metal using a bench-stable and readily accessible phosphonium salt. Deuterium labeling experiments and cyclic voltammetry measurements reveal that the difluoromethylation occurs via a SRN1-type mechanism. Substrate scope is broad, and various functional groups are tolerated (OH, NH2, amide, ester).
Heterocyclic compounds useful for kinase inhibition
-
Page/Page column 100, (2016/04/02)
Provided herein are compounds useful for kinase inhibition.
COMPOUNDS AND METHODS FOR IDENTIFYING AND/OR QUANTIFYING CARBONYLATED BIOMOLECULES
-
Page/Page column 16, (2012/12/13)
The subject invention provides compounds and methods for derivatizing, identifying and/or quantifying carbonylated bio molecules by using compounds of the invention. The invention provides compounds and a method of using such compounds for the analysis of
Novel photoreaction using diphenyl disulfide derivatives: Photoinduced oxidation of allyl alcohol
Tsuboi, Takaaki,Takaguchi, Yutaka,Tsuboi, Sadao
experimental part, p. 361 - 368 (2009/04/07)
Allyl alcohols are oxidized to acrylaldehydes using diphenyl disulfide derivatives upon photoirradiation. The reaction occurs via α-hydrogen abstraction by a sulfanyl radical. Interestingly, the oxidation reaction occurs in moderate yield when a dendrimer disulfide is used as a mediator.
