- Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin
-
Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.
- Bassetto, Marcella,Brancale, Andrea,Pasqualetto, Gaia,Pileggi, Elisa,Rozanowska, Malgorzata,Schepelmann, Martin,Varricchio, Carmine
-
supporting information
(2021/09/24)
-
- Phenanthroline functionalized polyacrylonitrile fiber with Pd(0) nanoparticles as a highly active catalyst for the Heck reaction
-
A series of polyacrylonitrile fibers (PANF) functionalized with nitrogen-containing ligands were prepared and then used to synthesize fiber-supported Pd(0) nanoparticle catalysts. The phenanthroline-functionalized PANF with immobilized Pd(0) nanoparticles (PANPhenF-Pd(0)) had the best catalytic activity for the Heck reaction under solvent-free conditions. The PANPhenF-Pd(0) efficiently stabilized the nanoparticles and they were well-dispersed with Pd(0) particle sizes of about 3 nm. The PANPhenF-Pd(0) structure was further characterized by a variety of instrumental methods. A probable mechanism based on the fiber's microenvironment is proposed for the Heck reaction catalyzed by PANPhenF-Pd(0). The PANPhenF-Pd(0) catalyst is easily recovered from the reaction system and can be used up to six times with only a slight decrease in catalytic activity and with low Pd leaching. The PANPhenF-Pd(0) catalyst also has excellent catalytic activity for gram-scale use.
- Xiao, Jian,Zhang, Haonan,Ejike, Anyaegbu Chima,Wang, Lu,Tao, Minli,Zhang, Wenqin
-
-
- Discovery of Novel Benzothiazepinones as Irreversible Covalent Glycogen Synthase Kinase 3β Inhibitors for the Treatment of Acute Promyelocytic Leukemia
-
Recently, irreversible inhibitors have attracted great interest in antitumors due to their advantages of forming covalent bonds to target proteins. Herein, some benzothiazepinone compounds (BTZs) have been designed and synthesized as novel covalent GSK-3β inhibitors with high selectivity for the kinase panel. The irreversible covalent binding mode was identified by kinetics and mass spectrometry, and the main labeled residue was confirmed to be the unique Cys14 that exists only in GSK-3β. The candidate 4-3 (IC50 = 6.6 μM) showed good proliferation inhibition and apoptosis-inducing ability to leukemia cell lines, low cytotoxicity on normal cell lines, and no hERG inhibition, which hinted the potential efficacy and safety. Furthermore, 4-3 exhibited decent pharmacokinetic properties in vivo and remarkably inhibited tumor growth in the acute promyelocytic leukemia (APL) mouse model. All the results suggest that these newly irreversible BTZ compounds might be useful in the treatment of cancer such as APL.
- Zhang, Peng,Min, Zhihui,Gao, Yang,Bian, Jiang,Lin, Xin,He, Jie,Ye, Deyong,Li, Yilin,Peng, Chao,Cheng, Yunfeng,Chu, Yong
-
p. 7341 - 7358
(2021/06/28)
-
- Larvicidal activity and in silico studies of cinnamic acid derivatives against Aedes aegypti (Diptera: Culicidae)
-
Cinnamic acid derivatives (CAD's) represent a great alternative in the search for insecticides against Aedes aegypti mosquitoes since they have antimicrobial and insecticide properties. Ae. aegypti is responsible for transmitting Dengue, Chikungunya, and Zika viruses, among other arboviruses associated with morbimortality, especially in developing countries. In view of this, in vitro analyses of n-substituted cinnamic acids and esters were performed upon 4th instar larvae (L4) of Ae. aegypti, as well as, molecular docking studies to propose a potential biological target towards this mosquitoes species. The larvicide assays proved that n-substituted ethyl cinnamates showed a more pronounced activity than their corresponding acids, in which p-chlorocinnamate (3j) presented a LC50 value of 8.3 μg/mL. Thusly, external morphologic alterations (rigid and elongated body, curved bowel, and translucent or darkened anal papillae) of mosquitoes’ group exposed to compound 3j, were observed by microscopy. In addition, an analytical method was developed for the quantification of the most promising analog by using high-performance liquid chromatography with UV detection (HPLC-UV). Molecular docking studies suggested that the larvicide action is associated with inhibition of acetylcholinesterase (AChE) enzyme. Therefore, expanding the larvicidal study with the cinnamic acid derivatives against the vector Ae. aegypti is important for finding search for more effective larvicides and with lower toxicity, since they have already shown good larvicidal properties against Ae. aegypti.
- Bezerra Fran?a, Saraliny,Carine Barros de Lima, Luana,Rychard da Silva Cunha, Cristhyan,Santos Anuncia??o, Daniela,Ferreira da Silva-Júnior, Edeildo,Ester de Sá Barreto Barros, Maria,José da Paz Lima, Dimas
-
-
- New coumarin/sulfocoumarin linked phenylacrylamides as selective transmembrane carbonic anhydrase inhibitors: Synthesis and in-vitro biological evaluation
-
Two novel series of phenylacrylamide linked coumarins and sulfocoumarins (6a-p, 8a-i, and 14a-g) were synthesized and evaluated against four physiologically relevant human carbonic anhydrases (hCAs, EC 4.2.1.1), isoforms hCA I, hCA II, hCA IX and hCA XII for their inhibitory action. All new compounds when screened for carbonic anhydrase inhibitory activity have shown selective inhibition towards the tumor associated isoforms hCA IX and XII over CA I and II, with inhibition constants in the submicromolar to low nanomolar range. Compound 6b and 14g exhibited significant inhibition with low nanomolar potency against hCA IX, whereas 6k was effective against hCA XII. Compounds 6b, 14g and 6k may be considered as lead molecules for future development of cancer therapeutics based on a novel mechanism of action.
- Angeli, Andrea,Arifuddin, Mohammed,Singh, Priti,Supuran, Claudiu T.,Swain, Baijayantimala
-
-
- Radical-Cation Vinylcyclopropane Rearrangements by TiO2Photocatalysis
-
Radical cation vinylcyclopropane rearrangements by TiO2 photocatalysis in lithium perchlorate/nitromethane solution are described. The reactions are triggered by oxidative single electron transfer, which is followed by immediate ring-opening of the cyclopropanes to generate distonic radical cations as unique reactive intermediates. This approach can also be applied to vinylcyclobutane, leading to the construction of six-membered rings. A stepwise mechanism via distonic radical cations is proposed based on preliminary mechanistic studies, which is supported by density functional theory calculations.
- Maeta, Naoya,Kamiya, Hidehiro,Okada, Yohei
-
supporting information
p. 6551 - 6566
(2020/07/14)
-
- Toward a Scalable Synthesis and Process for EMA401, Part II: Development and Scale-Up of a Pyridine- A nd Piperidine-Free Knoevenagel-Doebner Condensation
-
During route scouting for EMA401 (1), an angiotensin II type 2 antagonist, we identified the synthesis of key amino acid intermediate 2 via its cinnamic acid derivative 3 as a streamlined option. In general, cinnamic acids can be synthesized from the corresponding aldehydes by a Knoevenagel-Doebner condensation in pyridine with piperidine as an organocatalyst. We aimed to replace both of these reagents and found novel conditions involving toluene as the solvent and morpholine as the organocatalyst. Scale-up of the process allowed the production of 25 kg of cinnamic acid 3 that was of the quality required for process development of the subsequent phenylalanine ammonia lyase-catalyzed step. The modified conditions were found to be widely applicable to alternative aldehydes and thus are of relevance to practitioners of chemical scale-up.
- Hardegger, Leo A.,Humair, Roger,Sidler, Eric
-
p. 1756 - 1762
(2020/10/26)
-
- Design, synthesis and biological evaluation of (E)-5-styryl-1,2,4-oxadiazoles as anti-tubercular agents
-
Cinnamic acid and its derivatives are known for anti-tubercular activity. The present study reports the synthesis of cinnamic acid derivatives via bioisosteric replacement of terminal carboxylic acid with “oxadiazole”. A series of cinnamic acid derivatives (styryl oxadiazoles) were designed and synthesized in good yields by reaction of substituted cinnamic acids (2, 15a-15s) with amidoximes. The synthesized styryl oxadiazoles were evaluated in vitro for anti-tubercular activity against Mycobacterium tuberculosis (Mtb) H37Ra strain. The structure-activity relationship (SAR) study has identified several compounds with mixed anti-tubercular profiles. The compound 32 displayed potent anti-tubercular activity (IC50 = 0.045 μg/mL). Molecular docking studies on mycobacterial enoyl-ACP reductase enzyme corroborated well with the experimental findings providing a platform for structure based hit-to-lead development.
- Atmaram Upare, Abhay,Gadekar, Pradip K.,Sivaramakrishnan,Naik, Nishigandha,Khedkar, Vijay M.,Sarkar, Dhiman,Choudhari, Amit,Mohana Roopan
-
supporting information
p. 507 - 512
(2019/02/19)
-
- Substituted styrene preparation method
-
The invention belongs to the technical field of synthesis of chemical and medical intermediates, and relates to a substituted styrene preparation method, in particular to a method for preparing substituted styrene by using an ionic solution. In the method, the ionic solution is used as a solvent, and the reaction catalyzing efficiency is high. The ionic solution can be repeatedly used, industrialproduction cost is saved, and environment problems caused by a traditional solvent are solved favorably.
- -
-
Paragraph 0029-0031
(2019/02/26)
-
- Method for preparing styrene derivative from ionic liquid
-
The invention belongs to the technical field of chemical engineering and pharmaceutical intermediate synthesis and relates to a method for preparing a styrene derivative from ionic liquid. The methodhas advantages that by adoption of the ionic liquid as a solvent, high reaction catalyzing efficiency is achieved; due to reusability of the ionic liquid, industrial production cost is saved, and theenvironment problem caused by traditional solvents can be solved helpfully.
- -
-
Paragraph 0029-0031
(2019/04/06)
-
- A method for the preparation of substituted styrene ion solution method
-
The invention belongs to chemical and pharmaceutical intermediate synthesis technology field, relates to a process for preparing a substituted styrene ion solution method. The method takes the ionic liquid as solvent, reaction of high catalytic efficiency. The ionic liquid can be used repeatedly, save the industrialized production cost, and to facilitate the solution of the environmental problem of traditional solvent.
- -
-
Paragraph 0029; 0030; 0031
(2019/04/02)
-
- Compound capable of being strongly bound with alpha-synuclein aggregate, and preparation method and use of compound
-
The invention belongs to the technical field of medicine, and relates to a compound with a structural general formula I, and a preparation method and use of the compound. In the formula I, R1 is selected from phenyl, substituted phenyl, pyridyl and pyrimidinyl, and i is selected from 0 to 2, and is an integer; R2 is selected from alkyl, phenyl, substituted phenyl and 5-6-membered aromatic heterocyclic rings, and m is selected from 0 to 5, and is an integer; and R3 is selected from phenyl and substituted phenyl, and n is selected from 0 to 3, and is an integer. The compound comprises a cis-isomer, a trans-isomer or a mixture of the cis-isomer and the trans-isomer of the compound with the formula I structure. The compound can be strongly bound to an alpha-synuclein aggregate, can be used asan imaging tracer for the image technology such as PET, SPECT and the like, or can be used for preparing an imaging tracer and a composition containing the imaging tracer, the compound can be used forparticularly detecting Parkinson's disease or neurological disorders associated with the misfolding and aggregation of alpha-synuclein, and the compound has very good application prospects.
- -
-
Paragraph 0027; 0029; 0032; 0033; 0045-0047; 0153-0155
(2019/08/30)
-
- Discovery and anti-inflammatory evaluation of benzothiazepinones (BTZs) as novel non-ATP competitive inhibitors of glycogen synthase kinase-3β (GSK-3β)
-
Glycogen synthase kinase-3β (GSK-3β) has been identified to promote inflammation and its inhibitors have also been proven to treat some inflammatory mediated diseases in animal models. Non-ATP competitive inhibitors inherently have better therapeutical value due to their higher specificity than ATP competitive ones. In this paper, we designed and synthesized a series of new BTZ derivatives as non-ATP competitive GSK-3β inhibitors. Kinetic analysis revealed two typical compounds 6j and 3j showed the different non-ATP competitive mechanism of substrate competition or allosteric modulation to GSK-3β, respectively. As expected, the two compounds showed good specificity in a panel test of 16 protein kinases, even to the closest enzymes, like CDK-1/cyclin B and CK-II. The in vivo results proved that both compounds can greatly attenuate the LPS-induced acute lung injury (ALI) and diminish inflammation response in mice by inhibiting the mRNA expression of IL-1β and IL-6. Western blot analysis demonstrated that they negatively regulated GSK-3β, and the mechanism of the observed beneficial effects of the inhibitors may involve both the increased phosphorylation of the Ser9 residue on GSK-3β and protein expression of Sirtuin 1 (SIRT1). The results support that such novel BTZ compounds have a protective role in LPS-induced ALI, and might be attractive candidates for further development of inflammation pharmacotherapy, which greatly thanks to their inherently high selectivities by the non-ATP competitive mode of action. Finally, we proposed suggesting binding modes by Docking study to well explain the impacts of compounds on the target site.
- Gao, Yang,Zhang, Peng,Cui, Anfeng,Ye, De-Yong,Xiang, Meng,Chu, Yong
-
p. 5479 - 5493
(2018/10/09)
-
- Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors
-
A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50–50.5 nM), hCA IX (KIs of 1.8–228.5 nM), and hCA XII (KIs of 3.5–96.2 nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure–activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates.
- Angapelly, Srinivas,Ramya, P.V. Sri,Angeli, Andrea,Del Prete, Sonia,Capasso, Clemente,Arifuddin, Mohammed,Supuran, Claudiu T.
-
p. 5726 - 5732
(2017/10/09)
-
- LIGAND-EXCHANGEABLE NANOPARTICLES AND METHODS OF MAKING THE SAME
-
An aspect of the present disclosure is a nanocrystal that includes a nanocrystal core and a ligand coordinated to a surface of the nanocrystal core, where the ligand includes a functionalized aromatic molecule. In some embodiments of the present disclosure, the functionalized aromatic molecule may include at least one of cinnamic acid (CAH) and/or a functionalized CAH molecule.
- -
-
Paragraph 0061; 0063; 0067; 0068
(2018/01/18)
-
- Polystyrene supported palladium nanoparticles catalyzed cinnamic acid synthesis using maleic anhydride as a substitute for acrylic acid
-
Maleic anhydride was explored as a substitute for acrylic acid to synthesize cinnamic acids from aryl halides under heterogeneous palladium catalyzed conditions. The combined role of surface and impregnated catalyst together performed an upright engineering to hold in situ generated molecules on the surface and subsequently facilitate their interaction for the desired product synthesis. Overall, a surface mediated approach for cinnamic acid synthesis from maleic anhydride following a major unexplored pathway through catalyst promoted decarboxylation was critically investigated.
- Thakur, Vandna,Kumar, Sandeep,Das, Pralay
-
p. 3692 - 3697
(2017/09/07)
-
- Quinazoline compound containing cinnamamide structure and preparation method and application thereof
-
The invention discloses a quinazoline compound containing cinnamamide structure, geometric isomers of the quinazoline compound, and pharmaceutically acceptable salts, hydrates, solvates or prodrugs of the quinazoline compound, as well as a preparation method of the quinazoline compound. The invention also discloses application in the preparation of drugs for treating and/or preventing proliferative diseases, application in the preparation of drugs for treating and/or preventing cancers, and application in the preparation of drugs for treating and/or preventing prostate cancer, lung cancer and cervical cancer. Cyano groups are removed, side chains such as S-tetrahydrofuran-3-oxy, and activity for A549 has a significant increase. In-vitro antitumor activity screening for various EGFR (epidermal growth factor receptor) inhibitor highly-expressed cell strains shows high antitumor activity and selectivity, some compounds good in in-vitro antitumor activity are also selected for in-vivo activity testing of EGFR and VEGFR2/KDR. Experiments show that some compounds have efficient antitumor activity.
- -
-
Paragraph 0094; 0095
(2016/12/22)
-
- Design, synthesis, and docking studies of afatinib analogs bearing cinnamamide moiety as potent EGFR inhibitors
-
Two series of afatinib derivatives bearing cinnamamide moiety (10a-n and 11a-h) were designed, synthesized and evaluated for the IC50 values against four cancer cell lines (A549, PC-3, MCF-7 and Hela). Two selected compounds (10e, 10k) were further evaluated for the inhibitory activity against EGFR and VEGFR2/KDR kinases. Seven of the compounds showed excellent cytotoxicity activity and selectivity with the IC50 values in single-digit μM to nanomole range. Three of them are equal to more active than positive control afatinib against one or more cell lines. The most promising compound 10k showed the best activity against A549, PC-3, MCF-7 and Hela cancer cell lines and EGFR kinase, with the IC50 values of 0.07 ± 0.02 μM, 7.67 ± 0.97 μM, 4.65 ± 0.90 μM and 4.83 ± 1.28 μM, which were equal to more active than afatinib (0.05 ± 0.01 μM, 4.1 ± 2.47 μM, 5.83 ± 1.89 μM and 6.81 ± 1.77 μM), respectively. Activity of compounds 10e (IC50 9.1 nM) and 10k (IC50 3.6 nM) against EGFR kinase were equal to the reference compound afatinib (IC50 1.6 nM). Structure-activity relationships (SARs) and docking studies indicated that replacement of the aqueous solubility 4-(dimethylamino)but-2-enamide group by cinnamamide moiety didn't decrease the antitumor activity. The results suggested that methoxy substitution had a significant impact on the activity and methoxy substituted on C-4 or C-2,3,4 position was benefit for the activity.
- Tu, Yuanbiao,Ouyang, Yiqiang,Xu, Shan,Zhu, Yan,Li, Gen,Sun, Chao,Zheng, Pengwu,Zhu, Wufu
-
p. 1495 - 1503
(2016/03/15)
-
- HSP70 MODULATORS AND METHODS FOR MAKING AND USING THE SAME
-
The present invention provides compounds I and II and compositions thereof for use in the modulation of Hsp70. In some embodiments, the present invention provides a method for inhibiting Hsp70 activity. In some embodiments, the present invention provides a method of treating a subject suffering from or susceptible to a disease, disorder, or condition responsive to Hsp70 inhibition comprising administering to the subject a therapeutically effective amount of a provided compound. In some embodiments, the present invention provides a method for treating or preventing cancer in a subject suffering therefrom, comprising administering to a patient in need thereof a therapeutically effective amount of a provided compound.
- -
-
Paragraph 0463
(2015/12/24)
-
- Nucleophile-selective cross-coupling reactions with vinyl and alkynyl bromides on a dinucleophilic aromatic substrate
-
A nucleophile-selective cross-coupling reaction on an aromatic compound bearing two metal groups, Bpin and SnMe3, has been developed. Previously, only aryl bromides and iodides could be used as electrophilic components, but in this work, the scope could be extended to vinyl and alkynyl bromides as electrophiles. This means that the roles typical in Sonogashira couplings or Heck reactions of the aromatic ring as the dielectrophile coupling to vinyl and alkynyl metal species are reversed, which presents a new tool for organic synthesis. The first nucleophilic site to react is the stannyl group, and subsequently, a Suzuki-Miyaura cross-coupling reaction can take place on the same molecule.
- He, Lu-Ying,Schulz-Senft, Mathias,Thiedemann, Birk,Linshoeft, Julian,Gates, Paul J.,Staubitz, Anne
-
supporting information
p. 2498 - 2502
(2015/04/22)
-
- Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as inhibitors of the bacterial cell division protein FtsZ
-
In an attempt to discover potential antibacterial agents against the increasing bacterial resistance, novel cinnamaldehyde derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method, and their cell division inhibitory activity against four representative strains. In the in vitro antibacterial activity, the newly synthesized compounds generally displayed better efficacy against Staphylococcus aureus ATCC25923 than the others. In particular, compounds 3, 8 and 10 exerted superior or comparable activity to all the reference drugs. In the cell division inhibitory activity, all the compounds showed the same trend as their in vitro antibacterial activity, exhibiting better activity against S. aureus ATCC25923 than the other strains. Additionally, compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with an MIC value of below 1 1/4g/mL, over 256-fold better than all the reference drugs.
- Li, Xin,Sheng, Juzheng,Huang, Guihua,Ma, Ruixin,Yin, Fengxin,Song, Di,Zhao, Can,Ma, Shutao
-
-
- Synthesis and antibacterial activity of 4'3-O-(trans-β-arylacrylamido)carbamoyl azithromycin analogs
-
Novel 4'3-O-(trans-β-arylacrylamido)carbamoyl azithromycin analogs were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method. A majority of these derivatives maintained the activity of azithromycin against susceptible Streptococcus pyogenes and all the compounds demonstrated remarkably improved activity compared with the references against all the three phenotypes of resistant Streptococcus pneumoniae. In particular, compound 24 exhibited the most potent activity against susceptible Staphylococcus aureus (MIC = 0.5 μg/mL), S. pneumoniae (MIC = 0.06 μg/mL) and S. pyogenes (MIC = 0.25 μg/mL). The most active compound 7 (MIC = 0.015 μg/mL) against resistant S. pneumoniae expressing the mefA gene, exhibited 512 and 256-fold more potent activity than erythromycin and azithromycin, respectively. Compounds 28 (MIC = 0.5 μg/mL), 29 (MIC = 0.25 μg/mL) and 30 (MIC = 0.5 μg/mL) demonstrated potent activity against resistant S. pneumoniae expressing the ermB gene, which were 256, 512 and 256-fold better than the references, respectively.
- Yan, Mi,Ma, Xiaodong,Dong, Ruiqian,Li, Xin,Zhao, Can,Guo, Zhenzhen,Shen, Yan,Liu, Fang,Ma, Ruixin,Ma, Shutao
-
p. 506 - 515
(2015/10/06)
-
- Unravelling the structural and molecular basis responsible for the anti-biofilm activity of zosteric acid
-
The natural compound zosteric acid, or p-(sulfoxy)cinnamic acid (ZA), is proposed as an alternative biocide-free agent suitable for preventive or integrative anti-biofilm approaches. Despite its potential, the lack of information concerning the structural and molecular mechanism of action involved in its anti-biofilm activity has limited efforts to generate more potent anti-biofilm strategies. In this study a 43-member library of small molecules based on ZA scaffold diversity was designed and screened against Escherichia coli to understand the structural requirements necessary for biofilm inhibition at sub-lethal concentrations. Considerations concerning the relationship between structure and anti-biofilm activity revealed that i) the para-sulfoxy ester group is not needed to exploit the anti-biofilm activity of the molecule, it is the cinnamic acid scaffold that is responsible for anti-biofilm performance; ii) the anti-biofilm activity of ZA derivatives depends on the presence of a carboxylate anion and, consequently, on its hydrogen-donating ability; iii) the conjugated aromatic system is instrumental to the anti-biofilm activities of ZA and its analogues. Using a protein pull-down approach, combined with mass spectrometry, the herein-defined active structure of ZA was matrix-immobilized, and was proved to interact with the E. coli NADH:quinone reductase, WrbA, suggesting a possible role of this protein in the biofilm formation process.
- Cattò, Cristina,Dell'Orto, Silvia,Villa, Federica,Villa, Stefania,Gelain, Arianna,Vitali, Alberto,Marzano, Valeria,Baroni, Sara,Forlani, Fabio,Cappitelli, Francesca
-
-
- Cu/Fe-Cocatalyzed Formation of β-Ketophosphonates by a Domino Knoevenagel-Decarboxylation-Oxyphosphorylation Sequence from Aromatic Aldehydes and H-Phosphonates
-
A domino Knoevenagel-decarboxylation-alkene difunctionalization sequence has been developed for the conversion of benzaldehydes into β-ketophosphonates, catalyzed by a cooperative Cu/Fe system, whereby CP and CO bonds are formed simultaneously in a one-pot reaction. The reaction proceeds in good yields and with a broad substrate scope and environmentally benign conditions.
- Zhou, Mingxin,Zhou, Yao,Song, Qiuling
-
supporting information
p. 10654 - 10658
(2015/07/20)
-
- Simultaneous immobilization of a matrix containing palladium and phase transfer catalyst on silica nanoparticles: Application as a recoverable catalyst for the Heck reaction in neat water
-
Simultaneous covalent anchoring of a phosphonium-palladium complex/phase transfer catalyst matrix on the surface of silica nanoparticles and the application of the resulting catalyst in the Heck reaction of a variety of different haloarenes in neat aqueous media is described. This journal is the Partner Organisations 2014.
- Hajipour, Abdol R.,Azizi, Ghobad
-
p. 20704 - 20708
(2014/06/09)
-
- Novel cinnamic acid derivatives as antioxidant and anticancer agents: Design, synthesis and modeling studies
-
Cinnamic acids have been identified as interesting compounds with antioxidant, anti-inflammatory and cytotoxic properties. In the present study, simple cinnamic acids were synthesized by Knoevenagel condensation reactions and evaluated for the above biological activities. Compound 4ii proved to be the most potent LOX inhibitor. Phenylsubstituted acids showed better inhibitory activity against soybean LOX, and it must be noted that compounds 4i and 3i with higher lipophilicity values resulted less active than compounds 2i and 1i. The compounds have shown very good activity in different antioxidant assays. The antitumor properties of these derivatives have been assessed by their 1/IC50 inhibitory values in the proliferation of HT-29, A-549, OAW-42, MDA-MB-231, HeLa and MRC-5 normal cell lines. The compounds presented low antitumor activity considering the IC50 values attained for the cell lines, with the exception of compound 4ii. Molecular docking studies were carried out on cinnamic acid derivative 4ii and were found to be in accordance with our experimental biological results.
- Pontiki, Eleni,Hadjipavlou-Litina, Dimitra,Litinas, Konstantinos,Geromichalos, George
-
p. 9655 - 9674
(2014/08/05)
-
- TiCl4-mediated olefination of aldehydes with acetic acid and alkyl acetates: A stereoselective approach to (E)-α,β-unsaturated carboxylic acids and esters
-
A new method has been developed for the preparation of α,β- unsaturated carboxylic acids and corresponding esters with (E)-stereoselectivity via the TiCl4-mediated olefination of aldehydes. The method, which uses readily available acetic acid or its alkyl esters as active methylene partners, is more flexible and complementary to conventional routes in the preparation of (E)-cinnamic acid derivatives.
- Augustine, John Kallikat,Boodappa, Chandrakantha,Venkatachaliah, Srinivasa,Mariappan, Ayyampillai
-
p. 3503 - 3506
(2014/06/10)
-
- Influence of pendent alkyl chains on Heck and Sonogashira C-C coupling catalyzed with palladium(II) complexes of selenated Schiff bases having liquid crystalline properties
-
The effect of pendent alkyl chain lengths on Heck and Sonogashira coupling has been investigated for the first time using air and moisture insensitive complexes, [PdLCl] (1-4), of selenated Schiff bases (L = L1-L4), differing in length and number of pendent alkyl chain(s) and behaving as a (Se, N, O -) type of ligand. Differential scanning calorimetric (DSC) and polarized optical microscopic (POM) investigations show liquid crystalline nature of L1 and L2, which have one pendent alkyl chain of size C18 and C10 respectively. The yields of coupled products in catalytic Heck and Sonogashira coupling reactions were found good when amount of 1-4 used for them was 1.0 and 0.5 mol% respectively. The catalytic efficiency decreases with alkyl chain length of pendent arm of ligand for Heck coupling but remains unaffected in case of Sonogashira coupling. The in situ generation of palladium nanoparticles (NPs) protected with organoselenium species occurs in the case of Heck coupling. The length of pendent alkyl chain appears to control the dispersion and composition of these NPs and consequently the catalytic efficiency for Heck coupling. The black residues formed in the case of Sonogashira coupling catalyzed with 1 and 4 were found to have small fraction of NPs and a large proportion of big size aggregates. Their compositions for both the catalysts have been found nearly the same and due to predominance of aggregates, the efficiency remains almost unchanged on varying length of pendent alkyl chain. The two phase test for Heck coupling indicates that catalysis is largely heterogeneous.
- Rao, Gyandshwar Kumar,Kumar, Arun,Singh, Mahabir Pratap,Kumar, Ajay,Biradar, Ashok Manikrao,Singh, Ajai K.
-
-
- Synthesis of substituted nitroolefins: A copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids
-
A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tert-butyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.
- Rokade, Balaji V.,Prabhu, Kandikere Ramaiah
-
supporting information
p. 6713 - 6716
(2013/10/01)
-
- The [RPPhPd as a catalyst precursor for the heck cross-coupling reaction by in situ formation of stabilized Pd(0) nanoparticles
-
Pd(II) anionic, square planar complexes of the type [RPPhPdl, where X = Cl, Br, have been applied for the first time as a catalyst precursor for the Heck reaction carried out in DMF at 140 °C. The highest yield was obtained for the most reducible ones, [MePPhPdrl, in DMF in the presence of NaHCOas a base. It was found that during the reaction, phosphonium halide stabilized Pd(0) nanoparticles of about 10 nm, which have been formed in situ from the palladium(II) precursor and Pd(0) colloidal nanoparticles acts as the reservoir for Pd(II) species via activation of the metal surface through the oxidative addition of aryl halides. Georg Thieme Verlag Stuttgart New York.
- Hajipour, Abdol Reza,Azizi, Ghobad
-
supporting information
p. 254 - 258
(2013/03/13)
-
- The design, synthesis and in vitro immunosuppressive evaluation of novel isobenzofuran derivatives
-
The synthesis and biological evaluation of a series of novel isobenzofuran-based compounds are described. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and IMPDH type II inhibitor activity in vitro, as well as their structure-activity relationships were assessed. Several compounds demonstrated highly efficacious immunosuppressive properties, especially compounds 2d, 2e, 2h and 2j, which were superior to MPA, while compounds 2k, 2m, 2n, 4c and 5d exhibited an equipotent inhibitory activity compared to MPA. Generally, it was obviously demonstrated that α,β-unsaturated amides proved more potent than the diamide and urea series. The present study provides a guide for further research on development of safe and effective immunosuppressive agents.
- Yang, Na,Wang, Qing-He,Wang, Wen-Qian,Wang, Jian,Li, Feng,Tan, Shen-Peng,Cheng, Mao-Sheng
-
body text
p. 53 - 56
(2012/02/16)
-
- Monoamine oxidase inhibition by selected anilide derivatives
-
A series of anilide derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The most potent inhibitors among the derivatives that were initially evaluated were (2E)-N-(3-chlorophenyl)-3-phenylprop-2-enamide (2c) and (2E)-N-(3-bromophenyl)- 3-phenylprop-2-enamide (2d) with IC50 values of 0.53 μM and 0.45 μM, respectively. These derivatives exhibited reversible and selective inhibition of MAO-B with binding affinities 37 fold higher for MAO-B than for MAO-A. Analysis of the possible binding interactions of these inhibitors with active site models of human MAO-A and -B led to the design of phenolic and benzonitrile derivatives of 2c and 2d. Among these were (2E)-N-(3-chlorophenyl)- 3-(4-hydroxyphenyl)prop-2-enamide (7c) and (2E)-N-(3-bromophenyl)-3-(4- hydroxyphenyl)prop-2-enamide (7d) which inhibited MAO-B selectively and reversibly with IC50 values of 0.032 μM and 0.026 μM, respectively. These inhibitors were at least 14 fold more potent than 2c and 2d. This study concludes that N,3-diphenylprop-2-enamide is a suitable scaffold for the design of selective MAO-B inhibitors and structural modifications to enhance the binding affinities of the inhibitors for the MAO-B active site include substitution with halogens on the N-phenyl ring and substitution with hydroxyl and nitrile functional groups on the para and meta positions, respectively, of the C3 phenyl ring. Possible binding modes of these structures within the MAO-B active site are proposed with the emphasis on the interactions of the inhibitor halogens and the hydroxyl and nitrile functional groups with active site residues and water molecules.
- Legoabe, Lesetja,Kruger, Johann,Petzer, Anél,Bergh, Jacobus J.,Petzer, Jacobus P.
-
experimental part
p. 5162 - 5174
(2011/11/29)
-
- Environmentally benign and energy efficient methodology for condensation: An interesting facet to the classical Perkin reaction
-
We have reported use of biodegradable deep eutectic solvent (DES) based on choline chloride and urea, for the synthesis of cinnamic acid and its derivatives via Perkin reaction. The reaction proceeds efficiently under mild condition without use of additional catalyst with better yields. Ease of recovery and reusability of solvent with consistent activity makes this method efficient and environmentally benign. This method is also energy efficient and easy to handle.
- Pawar, Poonam Mahadev,Jarag, Krishna Jagannath,Shankarling, Ganapati Subray
-
experimental part
p. 2130 - 2134
(2011/10/03)
-
- Oxadiazole derivatives as S1P1 receptor agonists
-
New compounds having the chemical structure of formula (I) or pharmaceutically acceptable salts or N-oxides thereof wherein A is selected from the group consisting of -N-, -O- and -S-; B and C independently are selected from the group consisting of -N- and -O-, with the proviso that at least two of A, B and C are nitrogen atoms; G1 is selected from the group consisting of nitrogen atoms and -CRC- groups, wherein RC represents a hydrogen atom, a halogen atom, a C1-4 alkyl group or a C1-4 alkoxy group; R1 is selected from the group consisting of hydrogen atoms, C1-4 alkyl groups, C1-4 alkoxy groups, C3-4 cycloalkyl groups, and -NRdRe groups wherein Rd and Re are independently selected from hydrogen atoms and C1-4 alkyl groups; R2 and R3 are independently selected from the group consisting of hydrogen atoms and C1-4 alkyl groups; R4, R5 and R7 are independently selected from the group consisting of hydrogen atoms, halogen atoms, C1-4 alkyl groups, C1-4 alkoxy groups and C1-4 haloalkyl groups; R6 represents a C1-4 alkyl group or a C1-4 hydroxyalkyl group; or R6 is selected from the group consisting of -S(O)2-NRaRb groups, -(CRfRg)n-(CRhRi)x-(CRjRk)y-NRaRb groups, -(CH2)n-NRaRb groups, -O-(CH2)n-NRaRb groups, -(CH2)n-COOH groups, -(CH2)n-NRa-CO-Rb' groups, -(CH2)n-NRa-(CH2)p-(NH)q-SO-CH3 groups and -(CH2)n-CO-NRaRb groups, wherein n, p, x and y are each independently integers from 0 to 3, q is 0 or 1, Rf, Rg, Rh, Ri, Rj and Rk independently represent hydrogen atoms or halogen atoms, Rb' is selected from the group consisting of methylsulphonyl groups, C1-4 alkyl groups, C1-4 hydroxyalkyl groups, C1-4 carboxyalkyl groups, and C1-4 haloalkyl groups; Ra and Rb are independently selected from the group consisting of hydrogen atoms, methylsulphonyl groups, C1-4 alkyl groups, C1-4 hydroxyalkyl groups, C1-4 carboxyalkyl groups, and C1-4 haloalkyl groups, or Ra and Rb together with the nitrogen atom to which they are attached form a 4 to 6 membered, saturated heterocyclic group, which contains, as heteroatoms, one or two nitrogen atoms and which is substituted by a carboxyl group or a C1-4 carboxyalkyl group; or Rc together with R6 form a C5-8 carbocyclic ring optionally substituted by - NHR' wherein R' represents a hydrogen atom or a 61-4 carboxyalkyl group.
- -
-
Page/Page column 34
(2010/08/07)
-
- A facile method for synthesis of amine-functionalized mesoporous zirconia and its catalytic evaluation in Knoevenagel condensation
-
Amine-functionalized mesoporous zirconia was prepared by a co-condensation method using silane (aminopropyltrimethoxysilane, APTES) and zirconium butoxide. The materials were characterized by X-ray diffraction, BET surface area analysis, 13C magic angle spinning-nuclear magnetic resonance (NMR), Fourier-transfer infrared spectroscopy (FTIR), transmittance electron micrography (TEM), and CHN analysis. FTIR and NMR results revealed the successful grafting of organic amines onto the surface of zirconia. The catalytic activities were investigated for liquid phase Knoevenagel condensation of various aromatic aldehydes with diethyl malonate. The catalysts showed excellent yield of products at room temperature in solvent-free condition.
- Parida,Mallick, Sujata,Sahoo,Rana
-
experimental part
p. 226 - 232
(2010/08/06)
-
- Heterogeneous versus homogeneous palladium catalysts for ligandless Mizoroki-Heck reactions: A comparison of batch/microwave and continuous-flow processing
-
Mizoroki-Heck couplings of aryl iodides and bromides with butyl acrylate were investigated as model systems to perform transition-metal-catalyzed transformations in continuous-flow mode. As a suitable ligandless catalyst system for the Mizoroki-Heck coupl
- Glasnov, Toma N.,Findenig, Silvia,Kappe, C. Oliver
-
experimental part
p. 1001 - 1010
(2009/07/17)
-
- Investigating the existence of nonthermal/specific microwave effects using silicon carbide heating elements as power modulators
-
(Chemical Equation Presented) The use of passive heating elements made out of chemically inert sintered silicon carbide (SiC) allows microwave transparent or poorly absorbing reaction mixtures to be heated under microwave conditions. The cylindrical heating inserts efficiently absorb microwave energy and subsequently transfer the generated thermal energy via conduction phenomena to the reaction mixture. In the case of low to medium microwave absorbing reaction mixtures, the addition of SiC heating elements results in significant reductions (30-70%) in the required microwave power as compared to experiments performed without heating element at the same temperature. The method has been used to probe the influence of microwave power (electromagnetic field strength) on chemical reactions. Six diverse types of chemical transformations were performed in the presence or absence of a SiC heating element at the same reaction temperature but at different microwave power levels. In all six cases, the measured conversions/yields were similar regardless of whether a heating element was used or not. The applied microwave power had no influence on the reaction rate, and only the attained temperature governed the outcome of a specific chemical process under microwave conditions.
- Razzaq, Tahseen,Kremsner, Jennifer M.,Kappe, C. Oliver
-
p. 6321 - 6329
(2008/12/22)
-
- Synthesis, and biological evaluation of new 1,3,4-thiadiazolium-2-phenylamine derivatives against Leishmania amazonensis promastigotes and amastigotes
-
1,3,4-Thiadiazolium-2-aminide, which is a class of mesoionic compounds, were tested against promastigote and amastigote forms of Leishmania amazonensis. Parasites were assayed with or without the drugs in axenic media, using pentamidine isethionate as a reference drug. The very promising results showed us the most active compounds were the 4′- and 3′-methoxy derivatives against promastigote forms, while the highest activity against the amastigote forms was obtained with the 4′-fluor and 3′-bromo derivatives.
- Da Silva, Edson F.,Canto-Cavalheiro, Marilene M.,Braz, Viviane R.,Cysne-Finkelstein, Lea,Leon, Leonor L.,Echevarria, Aurea
-
p. 979 - 984
(2007/10/03)
-
- KOH-promoted reaction of C,O,O-tris(trimethylsilyl) ketene acetal with aldehydes: Practical and easy access to (E)-α,β-ethylenic carboxylic acids
-
The use of a catalytic amount of KOH has been found to be very efficient in promoting reaction of silylketene acetal 1 with aldehydes 2 to afford the corresponding (E)-α,β-ethylenic carboxylic acids 3 under very mild conditions.
- Lensen,Mouelhi,Bellassoued
-
p. 1007 - 1011
(2007/10/03)
-
- BENZAMIDINE DERIVATIVES
-
Benzamidine derivatives of the following formulae or analogs thereof, i. e., pharmaceutically acceptable salts thereof, are provided. These compounds or salts thereof have a blood-coagulation inhibiting effect based on an excellent effect of inhibiting the action of activated blood coagulation factor X, and they are useful as anticoagulants.
- -
-
-
- Hypoxic radiosensitizers: Substituted styryl derivatives
-
A number of novel styryl epoxides, N-substituted-styryl-ethanolamines, N-mono and N,N'-bis-(2-hydroxyethyl)-cinnamamides - analogues to the known radiosensitizers RSU- 1069, pimonidazole and etanidazole - display selective hypoxic radiosensitizing activity. The styryl group, especially when substituted by electron withdrawing groups, was found to be bioisosteric to the nitroimidazolyl functionality. The most active derivative 2-(2'-nitrophenyl)ethen-1-yl-oxirane 8a displayed a sensitizer enhancement ratio (SER) of 5 relative to misonidazole.
- Nudelman,Falb,Odesa,Shmueli-Broide
-
p. 619 - 625
(2007/10/02)
-
- Piperidine compounds and their use as antiarrhythmic agents
-
A piperidine derivative of general formula (I) or a pharmaceutically acceptable salt thereof: STR1 wherein STR2 is any of several specified aromatic-containing groups; X is selected from one of several hetero atom-containing groups or C2 alkylene or a cyano-containing group; and Q is phenyl, cyclohexyl, piperidinyl, tetrahydropyranyl, pyridyl, pyrrolyl, N-methylpyrrolyl, thienyl, furyl, 1-hexyl, or cyano; from 1 to 3 hydrogen atoms in Q may be independently substituted by alkyl of from 1 to 3 carbon atoms, perfluoroalkyl of from 1 to 3 carbon atoms, acylamino of from 1 to 6 carbon atoms, perfluoroacylamino of from 1 to 3 carbon atoms, alkoxy of from 1 to 3 carbon atoms, alkanesulfonylamino of from 1 to 3 carbon atoms, perfluoroalkanesulfonylamino of from 1 to 3 carbon atoms, acetoxy of from 1 to 3 carbon atoms, aminocarbonyl, aminosulfonyl, fluoro, chloro, cyano, hydroxy, nitro, amino, imidazolylmethyl, cinnamoylamino, p-fluorobenzoyl, cyanomethyl, cyanoethyl, methoxyacetoxy, alkoxycarbonyl of from 1 to 3 carbon atoms; 1 is an integer of from 0 to 1; m is an integer of from 0 to 1; n is an integer of from 0 to 6. The derivatives are useful as antiarrhythmic agents.
- -
-
-
- Method of eliminating protective groups
-
A method of deprotection which comprises reacting a compound having at least one of amino, hydroxyl, mercapto and carboxyl groups protected by a substituted or unsubstituted benzyloxycarbonyl group or by a substituted or unsubstituted benzyl group with zinc in a buffer, thereby splitting off the protective benzyloxycarbonyl or benzyl group.
- -
-
-
- Carboxypeptidase A-Catalyzed Hydrolysis of α-(Acylamino)cinnamoyl Derivatives of L-β-Phenyllactate and L-Phenylalaninate: Evidence for Acyl-Enzyme Intermediates
-
The (CPA) carboxypeptidase A-catalyzed hydrolysis of α-(acetylamino)- (1), α-(benzoylamino)- (2), or α-cinnamoyl ester (3) of L-β-phenyllactate manifested small values of both kcat and Kmapp.On the other hand, the corresponding amides of L-Phe showed enhanced kcat and unaffected Kmapp values.At -2 deg C, accumulation of an intermediate was observed spectrophotometrically immediately after mixing of 6x10-5 M CPA with 4x10-5 M 3.This is the most stable (in terms of half-life and Kmapp) intermediate ever reported for the CPA-catalyzed reactions.For 2 and 3, kcat was independent of pH over pH 5.5-9.5.Although attempts to trap the intermediate with external or intramolecular trapping reagents were unseccesful, the very small Kmapp and the pH independence of kcat for 2 and 3 provide evidence that shows that the accumulating intermediate is the anhydride acyl-CPA intermediate.The temperature dependence and the D2O effect were measured for the kcat values of 2 and 3.The different effects of the α-(acylamino)cynnamoyl groups on the kinetic parameters for esters and for peptides were explained in terms of a single mechanism with the intermediacy of an acyl-enzyme.
- Suh, Junghun,Cho, Wonhwa,Chung, Shin
-
p. 4530 - 4535
(2007/10/02)
-
- Choix des methodes pour la synthese univoque de carbures acetyleniques. Troisieme partie : Arylacetylenes et aryl-1 alcynes-1
-
The range of applicability of six syntheses of pure alkynes with one aryl group has been defined; a short review of other possible procedures is included.We have specified the best method to obtain selectively the alkynes Ar-CCH and Ar-CC-R, according to the nature of the substituents of the aryl group and according to the developed structure of the R group.It is thus possible to recommend with the largest probability of success the method to obtain, in homogenous series, alkynes corresponding to still more complicated structures.
- Mesnard, Danielle,Bernadou, Francoise,Miginiac, Leone
-
p. 3216 - 3245
(2007/10/02)
-
- Liquid crystal compositions containing cyanocinnamic acid esters
-
Liquid crystalline p-cyanocinnamic acid p'-n-alkoxyphenyl esters, and nematic liquid crystal compositions containing the same, useful for electro-optical devices, are described.
- -
-
-
- Cinnamamidohydantoins
-
A series of cinnamamidohydantoins are useful as anthelmintic agents.
- -
-
-