3943-97-3Relevant articles and documents
Mechanochemical Cycloreversion of Cyclobutane Observed at the Single Molecule Level
Pill, Michael F.,Holz, Katharina,Preu?ke, Nils,Berger, Florian,Clausen-Schaumann, Hauke,Lüning, Ulrich,Beyer, Martin K.
, p. 12034 - 12039 (2016)
Mechanochemical cycloreversion of cyclobutane is known from ultrasound experiments. It is, however, not clear which forces are required to induce the cycloreversion. In atomic force microscopy (AFM) experiments, on the other hand, it is notoriously difficult to assign the ruptured bond. We have solved this problem through the synthesis of tailored macrocycles, in which the cyclobutane mechanophore is bypassed by an ethylene glycol chain of specific length. This macrocycle is covalently anchored between a glass substrate and an AFM cantilever by polyethylene glycol linkers. Upon mechanical stretching of the macrocycle, cycloreversion occurs, which is identified by a defined length increase of the stretched polymer. The measured length change agrees with the value calculated with the external force explicitly included (EFEI) method. By using two different lengths for the ethylene glycol safety line, the assignment becomes unambiguous. Mechanochemical cycloreversion of cyclobutane is observed at forces above 1.7 nN.
Flavonoid glycosides from Rhazya orientalis
Itoh, Atsuko,Kumashiro, Tomoko,Tanahashi, Takao,Nagakura, Naotaka,Nishi, Toyoyuki
, p. 352 - 357 (2002)
Six new flavonoid glycosides; quercetin 3-O-α-L-rhamnopyranosyl(1→6)-[α-L-rhamnopyranosyl (1→2)]-(4-O-trans-p-coumaroyl)-β-D-galactopyranoside-7- OαL-rhamnopyranoside (1), quercetin 3-O-α-L-rhamnopyranosyl(1→6)-[α-L-rhamnopyranosyl (1→2)]-(3-O-trans-p-cou
Conjugation with dihydrolipoic acid imparts caffeic acid ester potent inhibitory effect on dopa oxidase activity of human tyrosinase
Micillo, Raffaella,Sirés-Campos, Julia,García-Borrón, José Carlos,Panzella, Lucia,Napolitano, Alessandra,Olivares, Conchi
, (2018)
Caffeic acid derivatives represent promising lead compounds in the search for tyrosinase inhibitors to be used in the treatment of skin local hyperpigmentation associated to an overproduction or accumulation of melanin. We recently reported the marked inhibitory activity of a conjugate of caffeic acid with dihydrolipoic acid, 2-S-lipoylcaffeic acid (LCA), on the tyrosine hydroxylase (TH) and dopa oxidase (DO) activities of mushroom tyrosinase. In the present study, we evaluated a more lipophilic derivative, 2-S-lipoyl caffeic acid methyl ester (LCAME), as an inhibitor of tyrosinase from human melanoma cells. Preliminary analysis of the effects of LCAME on mushroom tyrosinase indicated more potent inhibitory effects on either enzyme activities (IC50 = 0.05 ± 0.01 μM for DO and 0.83 ± 0.09 μM for TH) compared with LCA and the reference compound kojic acid. The inhibition of DO of human tyrosinase was effective (Ki = 34.7 ± 1.1 μM) as well, while the action on TH was weaker. Lineweaver–Burk analyses indicated a competitive inhibitor mechanism. LCAME was not substrate of tyrosinase and proved nontoxic at concentrations up to 50 μM. No alteration of basal tyrosinase expression was observed after 24 h treatment of human melanoma cells with the inhibitor, but preliminary evidence suggested LCAME might impair the induction of tyrosinase expression in cells stimulated with α-melanocyte-stimulating hormone. All these data point to this compound as a valuable candidate for further trials toward its use as a skin depigmenting agent. They also highlight the differential effects of tyrosinase inhibitors on the human and mushroom enzymes.
A drug delivery system based on switchable photo-controlled p-coumaric acid derivatives anchored on mesoporous silica
Beňová, Eva,Zeleňák, Vladimír,Halamová, Dá?a,Almá?i, Miroslav,Petrul'ová, Veronika,Psotka, Miroslav,Zeleňáková, Adriána,Ba?kor, Martin,Hornebecq, Virginie
, p. 817 - 825 (2017)
A stimuli-responsive drug delivery system consisting of mesoporous silica with its surface modified by p-coumaric acid derivatives (CA) as photo-switchable ligands was studied for the delivery of the non-steroidal anti-inflammatory drug (NSAID) naproxen. For this purpose, MCM-41 mesoporous silica material was prepared and post-synthetically modified by the grafting of a triethoxysilyl derivative of p-coumaric acid, which undergoes a reversible photo-dimerization under UV irradiation and creates the “valves” on the surface of silica allowing targeted opening/closing of the pores. Naproxen was encapsulated into grafted MCM-41 and drug release studies were performed in two different media, in a simulated gastric fluid (pH = 2) and in a simulated body fluid (pH = 7.4). Differences in drug release were observed after irradiation of the material using UV light at λ = 365 nm (closed pore configuration) and UV light at λ = 254 nm (opened pore configuration).
Ultrafast dynamics of isolated model photoactive yellow protein chromophores: "Chemical perturbation theory" in the laboratory
Vengris, Mikas,Larsen, Delmar S.,Van Der Horst, Michael A.,Larsen, Olaf F. A.,Hellingwerf, Klaas J.,Van Grondelle, Rienk
, p. 4197 - 4208 (2005)
Pump-probe and pump-dump probe experiments have been performed on several isolated model chromophores of the photoactive yellow protein (PYP). The observed transient absorption spectra are discussed in terms of the spectral signatures ascribed to solvation, excited-state twisting, and vibrational relaxation. It is observed that the protonation state has a profound effect on the excited-state lifetime of p-coumaric acid. Pigments with ester groups on the coumaryl tail end and charged phenolic moieties show dynamics that are significantly different from those of other pigments. Here, an unrelaxed ground-state intermediate could be observed in pump-probe signals. A similar intermediate could be identified in the sinapinic acid and in isomerization-locked chromophores by means of pump-dump probe spectroscopy; however, in these compounds it is less pronounced and could be due to ground-state solvation and/or vibrational relaxation. Because of strong protonation-state dependencies and the effect of electron donor groups, it is argued that charge redistribution upon excitation determines the twisting reaction pathway, possibly through interaction with the environment. It is suggested that the same pathway may be responsible for the initiation of the photocycle in native PYP.
Photoinduced Regioselective Olefination of Arenes at Proximal and Distal Sites
Ali, Wajid,Anjana, S. S.,Bhattacharya, Trisha,Chandrashekar, Hediyala B.,Goswami, Nupur,Guin, Srimanta,Maiti, Debabrata,Panda, Sanjib,Prakash, Gaurav,Saha, Argha,Sasmal, Sheuli,Sinha, Soumya Kumar
supporting information, p. 1929 - 1940 (2022/02/01)
The Fujiwara-Moritani reaction has had a profound contribution in the emergence of contemporary C-H activation protocols. Despite the applicability of the traditional approach in different fields, the associated reactivity and regioselectivity issues had
TRPV3 inhibitor and preparation method thereof
-
Paragraph 0240; 0241; 0242; 0243; 0244; 0245; 0246, (2021/04/10)
The invention discloses a TRPV3 inhibitor. The TRPV3 inhibitor is formed by sequentially connecting an R1 group, an R group and an R2 group, and the molecular structural general formula of the TRPV3 inhibitor is shown as a formula 1, wherein the structural formula of the R1 group is represented by a formula 2, R3 is selected from any one of -H, -OAc, -OH, a halogen group, -F3CO or a group containing a benzenesulfonyloxy group, and R4 is selected from any one of -H, -OAc or -OH; R1 and R2 are selected from alkyl or formula 3, R5 is selected from C or N, R6 is selected from any one of hydrogen, alkyl, halogen group or trifluoromethyl, R7 is selected from any one of hydrogen, halogen group, cyano group, nitro group or trifluoromethoxy group, and R8 is selected from hydrogen or halogen group. The invention also discloses a preparation method and application of the TRPV3 inhibitor. The TRPV3 inhibitor disclosed by the invention can specifically inhibit a TRPV3 ion channel and has huge scientific research and clinical values.
Prenylated trans-cinnamic esters and ethers against clinical fusarium spp.: Repositioning of natural compounds in antimicrobial discovery
Balmas, Virgilio,Carta, Paola,Casalini, Stefano,Chtioui, Wiem,Delogu, Giovanna,Dettori, Maria A.,Fabbri, Davide,Migheli, Quirico,Oufensou, Safa
, (2021/06/14)
Onychomycosis is a common nail infection mainly caused by species belonging to the F. oxysporum, F. solani, and F. fujikuroi species complexes. The aim of this study was to evaluate the in vitro susceptibility of six representative strains of clinically relevant Fusarium spp. toward a set of natural-occurring hydroxycinnamic acids and their derivatives with the purpose to develop naturally occurring products in order to cope with emerging resistance phenomena. By introducing a prenylated chain at one of the hydroxy groups of trans-cinnamic acids 1–3, ten prenylated derivatives (coded 4–13) were preliminarily investigated in solid Fusarium minimal medium (FMM). Minimal inhibitory concentration (MIC) and lethal dose 50 (LD50) values were then determined in liquid FMM for the most active selected antifungal p-coumaric acid 3,3′-dimethyl allyl ester 13, in comparison with the conventional fungicides terbinafine (TRB) and amphotericin B (AmB), through the quantification of the fungal growth. Significant growth inhibition was observed for prenylated derivatives 4–13, evidencing ester 13 as the most active. This compound presented MIC and LD50 values (62–250 μM and 7.8–125 μM, respectively) comparable to those determined for TRB and AmB in the majority of the tested pathogenic strains. The position and size of the prenylated chain and the presence of a free phenol OH group appear crucial for the antifungal activity. This work represents the first report on the activity of prenylated cinnamic esters and ethers against clinical Fusarium spp. and opens new avenues in the development of alternative antifungal compounds based on a drug repositioning strategy.
Dirigent Proteins Guide Asymmetric Heterocoupling for the Synthesis of Complex Natural Product Analogues
Kim, Stacie S.,Sattely, Elizabeth S.
supporting information, p. 5011 - 5021 (2021/05/04)
Phenylpropanoids are a class of abundant building blocks found in plants and derived from phenylalanine and tyrosine. Phenylpropanoid polymerization leads to the second most abundant biopolymer lignin while stereo- and site-selective coupling generates an array of lignan natural products with potent biological activity, including the topoisomerase inhibitor and chemotherapeutic etoposide. A key step in etoposide biosynthesis involves a plant dirigent protein that promotes selective dimerization of coniferyl alcohol, a common phenylpropanoid, to form (+)-pinoresinol, a critical C2 symmetric pathway intermediate. Despite the power of this coupling reaction for the elegant and rapid assembly of the etoposide scaffold, dirigent proteins have not been utilized to generate other complex lignan natural products. Here, we demonstrate that dirigent proteins from Podophyllum hexandrum in combination with a laccase guide the heterocoupling of natural and synthetic coniferyl alcohol analogues for the enantioselective synthesis of pinoresinol analogues. This route for complexity generation is remarkably direct and efficient: three new bonds and four stereocenters are produced from two different achiral monomers in a single step. We anticipate our results will enable biocatalytic routes to difficult-to-access non-natural lignan analogues and etoposide derivatives. Furthermore, these dirigent protein and laccase-promoted reactions of coniferyl alcohol analogues represent new regio- and enantioselective oxidative heterocouplings for which no other chemical methods have been reported.
Synthesis and Evaluation of PPARδAgonists That Promote Osteogenesis in a Human Mesenchymal Stem Cell Culture and in a Mouse Model of Human Osteoporosis
Kress, Brian J.,Kim, Dong Hyun,Mayo, Jared R.,Farris, Jeffery T.,Heck, Benjamin,Sarver, Jeffrey G.,Andy, Divya,Trendel, Jill A.,Heck, Bruce E.,Erhardt, Paul W.
, p. 6996 - 7032 (2021/05/29)
We synthesized a directed library of compounds to explore the structure-activity relationships of peroxisome proliferator-activated receptor δ(PPARδ) activation relative to mesenchymal stem cell (MSC) osteogenesis. Our scaffold used para-substituted cinnamic acids as a polar headgroup, a heteroatom and heterocycle core connecting units, and substituted phenyl groups for the lipophilic tail. Compounds were screened for their ability to increase osteogenesis in MSCs, and the most promising were examined for subunit specificity using a quantitative PPAR transactivation assay. Six compounds were selected for in vivo studies in an ovariectomized mouse model of human postmenopausal osteoporosis. Four compounds improved bone density in vivo, with two (12d and 31a) having activity comparable to that of GW0742, a well-studied PPARδ-selective agonist. 31a (2-methyl-4-[N-methyl-N-[5-methylene-4-methyl-2-[4-(trifluoromethyl)phenyl]thiazole]]aminocinnamic acid) had the highest selectivity for PPARδcompared to other subtypes, its selectivity far exceeding that of GW0742. Our results confirm that PPARδis a new drug target for possible treatment of osteoporosis via in situ manipulation of MSCs.
