cas 39856-08-1, 3,4-DIMETHOXYCINNAMOYL CHLORIDE

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Quorum sensing and nf-κb inhibition of synthetic coumaperine derivatives from piper nigrum
Bacterial communication, termed Quorum Sensing (QS), is a promising target for virulence attenuation and the treatment of bacterial infections. Infections cause inflammation, a process regulated by a number of cellular factors, including the transcription Nuclear Factor kappa B (NF-κB); this factor is found to be upregulated in many inflammatory diseases, including those induced by bacterial infection. In this study, we tested 32 synthetic derivatives of coumaperine (CP), a known natural compound found in pepper (Piper nigrum), for Quorum Sensing Inhibition (QSI) and NF-κB inhibitory activities. Of the compounds tested, seven were found to have high QSI activity, three inhibited bacterial growth and five inhibited NF-κB. In addition, some of the CP compounds were active in more than one test. For example, compounds CP-286, CP-215 and CP-158 were not cytotoxic, inhibited NF-κB activation and QS but did not show antibacterial activity. CP-154 inhibited QS, decreased NF-κB activation and inhibited bacterial growth. Our results indicate that these synthetic molecules may provide a basis for further development of novel therapeutic agents against bacterial infections.
Baruch, Yifat,Gopas, Jacob,Kadosh, Yael,Kumar, Rajendran Saravana,Kushmaro, Ariel,Muthuraman, Subramani,Yaniv, Karin
supporting information

(2021/05/28)

Cinnamyl-containing rupestonic acid methyl ester derivative as well as preparation method and application of rupestonic acid methyl ester derivative
The invention relates to a cinnamyl-containing rupestonic acid methyl ester derivative as well as a preparation method and application thereof, the derivative is prepared by the following steps: reacting rupestonic acid with dimethyl sulfate to obtain rupestonic acid methyl ester, and then obtaining 2-hydroxyl rupestonic acid methyl ester under the oxidation of camphor sulfonyl acridine. and then reacting with cinnamyl chloride under the catalysis of DMAP to obtain 20 rupestonic acid methyl ester derivatives containing cinnamyl groups. The method has the advantages of mild reaction conditions and simple experimental steps. The obtained 1d-20d rupestonic acid methyl ester derivatives containing the cinnamyl groups are subjected to a preliminary in-vitro anti-influenza A H3N2 virus activity test. Experimental results show that the compounds show good activity in 7d, 15d and 18d, and can be used as drugs for resisting influenza A H3N2 virus.
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Paragraph 0154-0155; 0158

(2021/06/02)

In quest of small-molecules as potent non-competitive inhibitors against influenza
A series of scaffolds namely aurones, 3-indolinones, 4-quinolones and cinnamic acid-piperazine hybrids, was designed, synthesized and investigated in vitro against influenza A/H1N1pdm09 virus. Designed molecules adopted different binding mode i.e., in 430-cavity of neuraminidase, unlike sialic acid and oseltamivir in molecular docking studies. All molecules reduced the viral titer and exhibited non-cytotoxicity along with cryo-protective property towards MDCK cells. Molecules (Z)-2-(3′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2f), (Z)-2-(4′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2g) and 2-(2′-Methoxy-phenyl)-1H-quinolin-4-one (3a) were the most interesting molecules identified in this research, endowed with robust potencies showing low-nanomolar EC50 values of 4.0 nM, 6.7 nM and 4.9 nM, respectively, compared to reference competitive and non-competitive inhibitors: oseltamivir (EC50 = 12.7 nM) and quercetin (EC50 = 0.56 μM), respectively. Besides, 2f, 2g and 3a exhibited good neuraminidase inhibitory activity in sub-micromolar range (IC50 = 0.52 μM, 3.5 μM, 1.3 μM respectively). Moreover, these molecules were determined as non-competitive inhibitors similar to reference non-competitive inhibitor quercetin unlike reference competitive inhibitor oseltamivir in kinetics studies.
Malbari, Khushboo,Saha, Priyanka,Chawla-Sarkar, Mamta,Dutta, Shanta,Rai, Swita,Joshi, Mamata,Kanyalkar, Meena
(2021/07/19)

Double asymmetric intramolecular aza-Michael reaction: a convenient strategy for the synthesis of quinolizidine alkaloids
A new methodology to access the quinolizidine skeleton in an asymmetric fashion was devised. It involves two consecutive intramolecular aza-Michael reactions of sulfinyl amines bearing a bis-enone moiety, in turn generated by a monodirectional cross metat
Alzuet-Pi?a, Gloria,Escolano, Marcos,Sánchez-Roselló, María,Torres, Javier,del Pozo, Carlos
supporting information
p. 8740 - 8745
(2021/10/22)

Aziridine-2-carboxylic acid derivatives and its open-ring isomers as a novel PDIA1 inhibitors
[Figure not available: see fulltext.] Acyl derivatives of aziridine-2-carboxylic acid have been synthesized and tested as PDIA1 inhibitors. Calculations of charge value and distribution in aziridine ring system and some alkylating agents were performed. For the first time was found that acyl derivatives of aziridine-2-carboxylic acid are weak to moderately active PDIA1 inhibitors.
Leite, Irena,Andrianov, Victor,Zelencova-Gopejenko, Diana,Loza, Einars,Kazhoka-Lapsa, Iveta,Domracheva, Ilona,Stoyak, Marta,Chlopicki, Stefan,Kalvins, Ivars
p. 1086 - 1106
(2022/01/12)

Design, synthesis and biological evaluation of novel carboline-cinnamic acid hybrids as multifunctional agents for treatment of Alzheimer's disease
Alzheimer's disease (AD) is a complex neurodegenerative disease with multiple pathological features. Multifunctional compounds able to simultaneously interact with several pathological components have been considered as a solution to treat the complex pathologies of neurodegenerative diseases. β-carboline and cinnamic acid have been extensively studied for their widespread biological effects in treatment of AD, further application is limited due to its poor solubility and high toxicity. Herein, a series of carboline-cinnamic acid hybrids was designed and synthesized to obtain new multifunctional molecules with low toxicity and good physicochemical properties. In particular, e3 and e12 exhibited significant inhibition of Aβ aggregation (inhibitory rate at 25 μM: 65% and 72% respectively), moderate BuChE inhibition, excellent neuroprotective effects and low neurotoxicity. Furthermore, in the AD mice model, e3 and e12 could restore learning and memory function to a comparable level to that of the control and did not exhibit any acute toxicity in vivo at a relatively high dose of 600 mg/kg. Thus, these new compounds can be further studied as multifunctional molecules for AD.
Feng, Feng,Jiang, Pan,Li, Qi,Liao, Qinghong,Liu, Wenyuan,Qu, Wei,Sun, Haopeng,Yan, Yuhui,Zhao, Yifan
(2020/04/22)

Separation and identification of an impurity from the istradefylline intermediate
Istradefylline is a selective adenosine antagonist for the A2a receptor, and it is used to treat the Parkinson's disease and improve dyskinesia in the early stage of the Parkinson's disease. An impurity in the istradefylline intermediate A1 (6-amino-1,3-diethyl-2,4-(1H,3H)-pyrimidinedione) was identified by high performance liquid chromatography (HPLC); it was separated by preparative HPLC and further characterized by UV, IR, MS, NMR, 2D NMR and single-crystal XRD analyses. The impurity was identified as (E)-N-ethyl-2-cyano-3-ethylamino-2-butenamide, which originated from the synthetic process of the intermediate A1. The structure of this impurity might affect the efficiency and safety of istradefylline; therefore, the research and control of this impurity are necessary for ensuring the quality of istradefylline.
Meng, Zihui,Wang, Hongyi,Wang, Yiyun,Xu, Haojie,Xu, Zhibin,Xue, Min,Zheng, Zhonghui
p. 14493 - 14499
(2020/04/27)

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
(2020/07/03)

Natural product derivatization with β-lactones, β-lactams and epoxides toward ‘infinite’ binders
β-Lactones, β-lactams and epoxides are privileged structural motifs found in both therapeutics and natural products. Herein we report several strategies for annulation of these motifs onto natural products that are not known to covalently modify their cellular targets. These strategies can facilitate identification of previously unidentified cellular targets or identify novel cellular targets of these natural products. The reported strategies include telescoped synthesis of β-lactones from allylic alcohols, nucleophile-catalyzed Michael aldol-β-lactonizations, and [2 + 2] β-lactam annulations with complex, commercially available alkene-containing natural products as substrates. A novel method for the tagging of phenolic natural products with epoxides is also reported.
Jouanneau, Morgan,Vellalath, Sreekumar,Kang, Guowei,Romo, Daniel
p. 3348 - 3354
(2019/05/17)

Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold
A general synthetic route to the unknown 1,3-dicarbonyl tropane derived curcumin analogues was developed. The method was based on the aldol condensation reaction (40–90 % yield, two steps without product isolation) and acylation of the resulting 2-benzylidenetropinones with substituted cinnamoyl cyanides (yields 41–91 %). Overall 18 new tropane derivatives featuring the characteristic curcuminoid hepta-1,6-dien-3,5-dione structure were synthesized and characterized. The range of the substituted aromatic rings in the prepared analogues included Ph, m-MeO-C6H4, 3,4-di-MeO-C6H3, 3,4,5-tri-MeO-C6H2, p-Br-C6H4, p-F-C6H4, p-CF3-C6H4, p-NO2-C6H4, 2-NO2-4,5-di-CH3O-C6H2, 2-NO2-4,5-O-CH2-O-C6H2, 3-MeO-4-[CH(CH3)-OEt]-C6H3, 3-MeO-4-OH-C6H3, p-MeO-C6H4, 4,5-O-CH2-O-C6H3, 3-MeO-4-MeOCOO. Two orthogonal protective groups for hydroxyl (acetal or carbonate), removable in acidic or basic conditions, were used for synthesizing curcuminoids with free phenolic groups (3-MeO-4-OH-C6H3).
Wolosewicz, Karol,Podgorska, Katarzyna,Rutkowska, Ewelina,Lazny, Ryszard
p. 4662 - 4674
(2019/08/01)

Phenylacrylate derivative and application thereof as neuroprotective drug
The invention discloses a phenylacrylate derivative and application thereof as a neuroprotective drug, the phenylacrylate derivative and a medicinal preparation thereof have a good curative treating effect on cranial nerve injury diseases such as cerebral apoplexy and related diseases, are low in acute toxicity and do not have the potential heart toxicity risk, and have a prominent technical effect and a substantial scientific progress compared with existing medicines. The phenylacrylate derivative is a compound represented by a general formula i or a salt thereof as shown in the specification.
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Paragraph 0069; 0070

(2019/05/02)

Synthesis, preliminarily biological evaluation and molecular docking study of new Olaparib analogues as multifunctional PARP-1 and cholinesterase inhibitors
A series of new Olaparib derivatives was designed and synthesized, and their inhibitory activities against poly (ADP-ribose) polymerases-1 (PARP-1) enzyme and cancer cell line MDA-MB-436 in vitro were evaluated. The results showed that compound 5l exhibited the most potent inhibitory effects on PARP-1 enzyme (16.10 ± 1.25 nM) and MDA-MB-436 cancer cell (11.62 ± 2.15 μM), which was close to that of Olaparib. As a PARP-1 inhibitor had been reported to be viable to neuroprotection, in order to search for new multitarget-directed ligands (MTDLs) for the treatment of Alzheimer’s disease (AD), the inhibitory activities of the synthesized compounds against the enzymes AChE (from electric eel) and BChE (from equine serum) were also tested. Compound 5l displayed moderate BChE inhibitory activity (9.16 ± 0.91 μM) which was stronger than neostigmine (12.01 ± 0.45 μM) and exhibited selectivity for BChE over AChE to some degree. Molecular docking studies indicated that 5l could bind simultaneously to the catalytic active of PARP-1, but it could not interact well with huBChE. For pursuit of PARP-1 and BChE dual-targeted inhibitors against AD, small and flexible non-polar groups introduced to the compound seemed to be conducive to improving its inhibitory potency on huBChE, while keeping phthalazine-1-one moiety unchanged which was mainly responsible for PARP-1 inhibitory activity. Our research gave a clue to search for new agents based on AChE and PARP-1 dual-inhibited activities to treat Alzheimer’s disease.
Gao, Cheng-Zhi,Dong, Wei,Cui, Zhi-Wen,Yuan, Qiong,Hu, Xia-Min,Wu, Qing-Ming,Han, Xianlin,Xu, Yao,Min, Zhen-Li
p. 150 - 162
(2018/11/30)

Pyridazinone derivative, and preparation method and medical application thereof
The invention provides a pyridazinone derivative, and a preparation method and a medical application thereof. O-formylbenzoic acid used as a raw material reacts with dimethyl phosphite to obtain dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate, the dimethyl (3-oxo-1,3-dihydroisobenzofuran-1-yl)phosphonate reacts with 3-cyano-4-fluorobenzaldehyde in the presence of triethylamine to prepare (Z,E)-2-fluoro-5-[(3-oxoisobenzofuran-1(3H)-ylidene)methyl]benzonitrile, and the (Z,E)-2-fluoro-5-[(3-oxoisobenzofuran-1(3H)-ylidene)methyl]benzonitrile is reduced by hydrazine hydrate to prepare 2-fluoro-5-[(4-oxo-3,4-dihydropyridazin-1-yl)methyl]benzoic acid; and benzaldehyde or substituted aromatic formaldehyde or furfural used as a raw material and malonic acid undergo a Knoevenagel reaction to obtain cinnamic acid or substituted cinnamic acid or furan-2-acrylic acid, the cinnamic acid or substituted cinnamic acid or furan-2-acrylic acid and 1-tert-butoxycarbonylpiperazine undergo an amidation reaction, a tert-butoxycarbonyl group is removed from the obtained amidation product in the presence of trifluoroacetic acid, and the obtained product and the 2-fluoro-5-[(4-oxo-3,4-dihydropyridazin-1-yl)methyl]benzoic acid undergo the amidation reaction to obtain a series of (E)-4-{3-[4-[(3-substituted aryl)acryloyl]piperazin-1-carbonyl]-4-fluorobenzyl}-2H-pyridazin-1-one derivatives. Results of preliminary pharmacological activity screening show that the compound represented by a general formula shown in the present invention has a certain in-vitro PARP-1 inhibition ability and a certain in-vitro tumor cell proliferation resisting activity. The structural general formula of compound is shown in the description; and in the general formula, Ar is selected from two formulas also shown in the description, and R1, R2, R3, R3, R4 and R5 can be the hydrogen atom, the fluorine atom, the chlorine atom, the bromine atom, a methyl group, a methoxy group, a tetrafluoromethyl group and a nitro group.
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Paragraph 0048; 0053

(2019/10/07)

Method for preparing hydroxyl-2(1H)-quinolinone
The invention discloses a method for preparing hydroxyl-2(1H)-quinolinone, and belongs to the field of organic chemistry. The method comprises the following steps: enabling an aminophenylboric acid compound and trans-beta-aryl acryloyl chloride to react under the existence of triethylamine or pyridine so as to generate a trans-amide intermediate, and then carrying out temperature rising reaction in an organic solvent under the existence of aluminum chloride anhydrous and B(C6F5)3; cooling after completing the reaction, and adding hydrogen peroxide for oxidization, thus obtaining the hydroxyl-2(1H)-quinolinone. The method disclosed by the invention has the advantages that raw materials are easy to obtain, hydroxyl quinolinone products in different positions can be obtained through differentinitial raw materials, and an existing synthetic route is enriched.
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Paragraph 0067; 0068; 0069; 0070

(2018/03/28)

Synthesis of a series of benzothiazole amide derivatives and their biological evaluation as potent hemostatic agents
A series of benzothiazole amide derivatives were synthesized through a facile and efficient method via a nucleophilic acyl substitution reaction between 2-aminobenzothiazole and various cinnamic acid compounds. The obtained products exhibited good thermal stabilities. All compounds were evaluated for their in vitro hemostatic activities using the commercially available standard drug etamsylate as a positive control. The results showed that compound Q2 had a significant partial coagulation activity, reduced capillary permeability at 5, 10 and 50 μmol L-1, activated thrombin activity, and a more potent platelet aggregation activity than the positive control group (etamsylate, up to 1283.9 times in the nanomole range). A molecular modeling study revealed that compound Q2 was a competitive thrombin activator. Therefore, Q2 may be a potential lead for further biological screening and for the generation of drug molecules. Moreover, the structure-activity relationship of the prepared compounds is also discussed herein.
Nong, Wenqian,Zhao, Anran,Wei, Jinrui,Cheng, Hui,Luo, Xuan,Lin, Cuiwu
p. 6231 - 6241
(2018/02/19)

Cinnamoyl-oxaborole amides: Synthesis and their in vitro biological activity
Due to the increased interest in their application in the treatment of infectious diseases, boron-containing compounds have received a significant coverage in the literature. Herein, a small set of novel cinnamoly-oxaborole amides were synthesized and screened against nagana Trypanosoma brucei brucei for antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50 value of 0.086 μM against T. b. brucei without obvious inhibitory activity against HeLa cell lines. The same series was also screened against other human pathogens, including Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), for which moderate to weak activity (10 to >125 μM) was observed. Similarly, these compounds exhibited moderate activity against the human protozoal pathogen Trichomonas vaginalis with no observed effect on common microbiome bacterial species. The cross-species inhibitory activity presents the possibility of these compounds serving as broad-spectrum antibiotics for these prevalent three human pathogens.
Gumbo, Maureen,Beteck, Richard M.,Mandizvo, Tawanda,Seldon, Ronnett,Warner, Digby F.,Hoppe, Heinrich C.,Isaacs, Michelle,Laming, Dustin,Tam, Christina C.,Cheng, Luisa W.,Liu, Nicole,Land, Kirkwood M.,Khanye, Setshaba D.
(2018/09/26)

Synthesis of coumarin derivatives and their cytoprotective effects on t-BHP-induced oxidative damage in HepG2 cells
Coumarins are ubiquitous in higher plants and exhibit various biological actions. The aim of this study was to investigate the structure-activity relationships of coumarin derivatives on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in human hepatoma HepG2 cells. A series of coumarin derivatives were prepared and assessed for their cytoprotective effects. Among these, a caffeoyl acid-conjugated dihydropyranocoumarin derivative, caffeoyllomatin, efficiently protected against cell damage elicited by t-BHP. Our findings suggest that caffeoyllomatin appears to be a potent cytoprotective agent.
Ando, Tomomi,Nagumo, Mina,Ninomiya, Masayuki,Tanaka, Kaori,Linhardt, Robert J.,Koketsu, Mamoru
supporting information
p. 2422 - 2425
(2018/06/20)

Stereocontrolled Synthesis of trans/ cis-2,3-Disubstituted Cyclopropane-1,1-diesters and Applications in the Syntheses of Furanolignans
A new Michael addition/intramolecular alkylation sequence of (Z)-3-(2-bromo-3-arylacryloyl)oxazolidin-2-ones and malonates was developed. By a simple switch of the reaction conditions including the base promoter, solvent, and reaction temperature, both of the cis- and trans-isomers of a series of oxazolidinone-containing 2,3-disubstituted cyclopropane-1,1-diesters could be obtained in good-to-excellent yields and with an excellent diastereoselectivity. The utility of the cyclopropane products was demonstrated in the diastereoselective syntheses of (±)-urinaligran and a stereoisomer of (±)-virgatusin involving the AlCl3-promoted [3+2] annulation with veraldehyde or piperonal as the key step.
Shen, Yue,Chai, Jun,Yang, Gaosheng,Chen, Wenlong,Chai, Zhuo
supporting information
p. 12549 - 12558
(2018/10/09)

HIGHLY EFFICIENT NRF2 ACTIVATORS-CO-RELEASING MOLECULE HYBRIDS, THEIR USE IN THE TREATMENT OF INFLAMMATORY OR CARDIOVASCULAR DISEASES AND THEIR PROCESS OF PREPARATION
The present invention relates to highly efficient Nrf2 activators-CO-releasing molecules of formula (I) and (II) capable of increasing HO-1 protein expression and simultaneously releasing CO, their synthesis and their use in therapeutic applications, in p
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Page/Page column 31

(2017/04/11)

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)

Synthesis of piplartine analogs and preliminary findings on structure–antimicrobial activity relationship
In this work it is described the synthesis, characterization and antimicrobial and toxicity evaluation of a series of analogs of piplartine, a piperamide found in Piper sp. The compounds structures were confirmed by infrared spectroscopy, 1H, 13C nuclear magnetic resonance, high resolution mass spectroscopy and were evaluated against strains of Candida spp., Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Derivative 24 was almost four-fold more potent (IC50: 48.83 μM) and five-fold less toxic (SI > 3) than piplartine (IC50: 189.2 μM; SI: 0.21) against Candida krusei, as well as two-fold more potent than fluconazole (IC50: 104.48 μM). This compound was also active against Candida tropicalis at 97.67 μM. Benzoyl derivative 17 was three-fold more potent (IC50: 85.2 μM) and more than five-fold less toxic (CC50: 231.71 μM) than piplartine (IC50: 315.33 μM and CC50: 41.14 μM) against Staphylococcus aureus. Given these findings, we have found analogs of piplartine which can be assumed as prototypes for the optimization and the development of new antimicrobial (compounds 24 and 17) agents.
Fregnan, Antonio Maciel,Brancaglion, Guilherme Andrade,Galv?o, Alexandre Francisco Cerqueira,D’Sousa Costa, Cinara Oliveira,Moreira, Diogo Rodrigo Magalh?es,Soares, Milena Botelho Pereira,Bezerra, Daniel Pereira,Silva, Naiara Chaves,de Souza Morais, Stella Maria,Oliver, Josidel Concei??o,Dias, Amanda Latercia Tranches,Coelho, Luiz Felipe Leomil,Carvalho, Diogo Teixeira,Dias, Danielle Ferreira,de Souza, Thiago Belarmino
p. 603 - 614
(2017/02/15)

Synthesis and in?vitro and in?vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids
Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in?vitro and in?vivo. The most potent compound, 5c, arrested HepG2 cells (IC50?=?4.23?±?0.79?μM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins. The downstream mitochondrial p53 translocation was also significantly activated, accompanied by an increase of the caspase-9, caspase-3 activation. These data imply that bergenin/cinnamic acid hybrids could serve as novel Akt/Bcl-2 inhibitors for further preclinical studies.
Liang, Chengyuan,Pei, Shaomeng,Ju, Weihui,Jia, Minyi,Tian, Danni,Tang, Yonghong,Mao, Gennian
p. 319 - 328
(2017/04/11)

Synthesis and biological evaluation of a new series of cinnamic acid amide derivatives as potent haemostatic agents containing a 2-aminothiazole substructure
Ten new cinnamic acid derivatives containing a 2-aminothiazole substructure were designed and synthesized. This series of compounds exhibited good thermostabilities as demonstrated by thermogravimetric analysis. In coagulation assays (prothrombin time, activated partial thromboplastin time and thrombin time) in vitro, most compounds demonstrated excellent activities to promote blood coagulation. Among the studied series, compounds N1, N4, N5 and W5 exhibited a significant coagulation activity. Further studies indicated that compound N5 (IC50 = 1.87 μmol/L) displayed the most suitable efficacy of promoting platelet aggregation than the clinically used haemostatic drug etamsylate (IC50 = 46.22 μmol/L). Furthermore, the relationship between the functional groups of the compounds and the corresponding blood coagulant activity was explored in this study.
Nong, Wenqian,Zhao, Anran,Wei, Jinrui,Lin, Xiao,Wang, Lisheng,Lin, Cuiwu
supporting information
p. 4506 - 4511
(2017/09/12)

Triclosan-caffeic acid hybrids: Synthesis, leishmanicidal, trypanocidal and cytotoxic activities
The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eight compounds were active against L. (V) panamensis (18–23, 26 and 30) and eight of them against T. cruzi (19–22, 24 and 28–30) with EC50 values lower than 40 μM. Compounds 19–22, 24 and 28–30 showed higher activities than benznidazole (BNZ). Esters 19 and 21 were the most active compounds for both L. (V) panamensis and T. cruzi with 3.82 and 11.65 μM and 8.25 and 8.69 μM, respectively. Compounds 19–22, 24 and 28–30 showed higher activities than benznidazole (BNZ). Most of the compounds showed antiprotozoal activity and with exception of 18, 26 and 28, the remaining compounds were toxic for mammalian cells, yet they have potential to be considered as candidates for anti-trypanosomal and anti-leishmanial drug development. The activity is dependent on the length of the alkyl linker with compound 19, bearing a four-carbon alkyl chain, the most performing hybrid. In general, hydroxyl groups increase both activity and cytotoxicity and the presence of the double bond in the side chain is not decisive for cytotoxicity and anti-protozoal activity.
Otero, Elver,García, Elisa,Palacios, Genesis,Yepes, Lina M.,Carda, Miguel,Agut, Raúl,Vélez, Iván D.,Cardona, Wilson I.,Robledo, Sara M.
p. 73 - 83
(2017/10/16)

Copper-catalyzed highly selective synthesis of 2-benzyl- and 2-benzylidene-substituted benzo[: B] thiazinones from 2-iodophenylcinnamamides and potassium sulfide
An efficient and practical procedure for the synthesis of 2-benzyl- and 2-benzylidene-substituted benzo[b]thiazinones from easily available 2-iodophenylcinnamamides and potassium sulfide has been developed. In the presence of DBU, the reaction proceeds vi
Liu, Wenjuan,Min, Hao,Zhu, Xiaoming,Deng, Guobo,Liang, Yun
supporting information
p. 9804 - 9808
(2017/12/08)

Design, synthesis, molecular docking studies and anti-HBV activity of phenylpropanoid derivatives
In this work, a series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated. Most of the synthesized derivatives showed effective anti-HBV activity. And compound 4d-3 showed the most effective anti-HBV activity, performing strong potent inhibitory not only on the secretion of HBsAg (IC50 = 58.28 μM, SI = 23.26) and HBeAg (IC50 = 97.21 μM, SI = 13.95), but also on the HBV DNA replication (IC50 = 42.28 μM, SI = 32.06). The structure-activity relationships (SARs) of the derivatives had been discussed, which were useful for developing phenylpropanoid derivatives as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site was carried out to explore the molecular interactions and a molecular target for activity and a modified assay method measuring the interaction between our derivatives and HBcAg was investigated, indicating that the HBV core protein might be their potential target for anti-HBV. This study identified a new class of potent non-nucleoside anti-HBV agents.
Liu, Sheng,Li, Yubin,Wei, Wanxing,Wang, Kuiwu,Wang, Lisheng,Wang, Jianyi
p. 1 - 9
(2016/04/05)

Synthesis and biological evaluation of arylcinnamide linked combretastatin-A4 hybrids as tubulin polymerization inhibitors and apoptosis inducing agents
A series of new molecules have been designed based on a hybridization approach by combining the arylcinnamide and combretastatin pharmacophores. These were synthesized and evaluated for their cytotoxic activity, effect on inhibition of tubulin polymerization and apoptosis inducing ability. Most of the conjugates exhibited significant cytotoxic activity against some representative human cancer cell lines and two of the conjugates 6i and 6p displayed potent cytotoxicity with GI50 values of 56 nM and 31 nM respectively against the human breast cancer cell line (MCF-7). SAR studies revealed that 3,4-substitution on the phenyl ring of the cinnamide moiety is beneficial for enhanced cytotoxicity. Moreover, G2/M cell cycle arrest was induced by these conjugates (6i and 6p) apart from tubulin polymerization inhibition (IC50 of 1.97 μM and 1.05 μM respectively). Further, mitochondrial membrane potential, Annexin V-FITC and caspase-9 activation assays suggested that these conjugates induce cell death by apoptosis. Docking studies revealed that these conjugates interact and bind at the colchicine binding site of the tubulin.
Kamal, Ahmed,Bajee, Shaik,Lakshma Nayak, Vadithe,Venkata Subba Rao, Ayinampudi,Nagaraju, Burri,Ratna Reddy, Challa,Jeevak Sopanrao, Kapure,Alarifi, Abdullah
supporting information
p. 2957 - 2964
(2016/06/06)

Synthesis and biological evaluation of phenylpropanoid derivatives
In this work, a series of oxime ether phenylpropanoid derivatives were synthesized. Their anti-hepatitis B virus (HBV) activity in HepG 2.2.15 cells was determined, and anti-cancer potential against three human cancer cell lines was evaluated. All the synthesized derivatives showed great efficiency against HBV. Compound 4d demonstrated the most effective anti-HBV activity, performing strong potent inhibitory not only on the secretion of HBsAg (IC50?=?50.45?μM, SI?=?9.18) and HBeAg (IC50?=?50.11?μM, SI?=?9.24), but also on the HBV DNA replication (IC50?=?51.80?μM, SI?=?8.94). Besides, the synthetic compounds also displayed obvious anti-cancer activity. Moreover, the docking study of all synthesized compounds inside the related protein active site was conducted to explore the molecular interactions and a molecular target for activity using a MOE-docking technique. This study identified a new class of potent anti-HBV and anti-cancer agents.
Liu, Sheng,Li, Yubin,Wei, Wanxing,Wei, Jingchen
p. 1074 - 1086
(2016/07/06)

Synthesis and biological evaluation of N-cinnamoyl and mandelate metformin analogues
A series of N,N-dimethyl-N1-[3-(substituted phenyl)-1-oxo-2-propenyl]biguanides were synthesized by coupling a solution of metformin in pyridine with different cinnamoyl chloride derivatives in ether for 3 h in addition to synthesis of some five molecules of metformin-mandelates. All the synthesized cinnamoyl metformins and a few metformin-mandelates were characterized by IR, NMR and Mass spectroscopic techniques. All the synthesized compounds were also evaluated for their antioxidant activity by DPPH scavenging method and nitric oxide scavenging method. All the compounds exhibited good antioxidant activity.
Anitha Kumari,Bharathi,Prabhu,Ponnudurai
p. 1895 - 1898
(2016/07/06)

Design, synthesis and biological evaluation of novel primaquine-cinnamic acid conjugates of the amide and acylsemicarbazide type
In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a-k) or via a spacer (compounds 7a-k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a-k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a-k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c-e), benzodioxole (7f), p-Cl (7g) and m-CF3 (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%-89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC50 = 10 μM). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates.
Pavi?, Kristina,Perkovi?, Ivana,Gilja, Petra,Kozlina, Filip,Ester, Katja,Kralj, Marijeta,Schols, Dominique,Hadjipavlou-Litina, Dimitra,Pontiki, Eleni,Zorc, Branka
(2016/12/16)

4-carbonyl-2-butene acid compound and use thereof
The invention provides a 4-carbonyl-2-butene acid compound with good inhibition activity against PA_N. The compound has a general formula (I), wherein R1 represents C1-C4 alkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl; and R2 represents hydroxy or substituted amino. The invention also relates to a medicine composition with the compound as an active component, and an application of the compound and the medicine composition provided by the invention in treating influenza.
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Paragraph 0128-0130

(2016/10/27)

All trans 1-(3-arylacryloyl)-3,5-bis (pyridin-4-ylmethylene)piperidin-4-ones as curcumin-inspired antineoplastics
A series of eleven N-acryloyl/N-cinnamoyl 3,5-bis(pyridin-4-yl)methylene-4-piperidones were synthesized as curcumin-based candidate antineoplastic agents. The cytostatic potency of these compounds was evaluated against three representative cell lines and all compounds were found to exhibit significant anti-cancer cell activity in vitro. QSAR studies using several physicochemical parameters and 50% inhibitory concentration (IC50) values resulted in certain important correlations which will aid design of more potent analogs. Representative test compounds were investigated in the NCI 60-cell line panel where they were found to display a profound cytotoxicity. These compounds were also potent anti-oxidants and inhibitors of human topoisomerase II±. Representative compounds were well-tolerated by human fibroblasts and by mice during the survival/toxicity studies.
Paul, Nawal K.,Jha, Mamta,Bhullar, Khushwant S.,Rupasinghe, H.P. Vasantha,Balzarini, Jan,Jha, Amitabh
p. 461 - 470
(2015/03/05)

Design, synthesis, biological evaluation and molecular docking studies of phenylpropanoid derivatives as potent anti-hepatitis B virus agents
A series of phenylpropanoid derivatives were synthesized, and their anti-hepatitis B virus (HBV) activity was evaluated in HepG 2.2.15 cells. Most of the synthesized derivatives showed effective anti-HBV activity. Of these compounds, compound 4c-1 showed the most potent anti-HBV activity, demonstrating potent inhibitory effect not only on the secretion of HBsAg (IC50 = 14.18 μM, SI = 17.85) and HBeAg (IC50 = 6.20 μM, SI = 40.82) secretion but also HBV DNA replication (IC50 = 23.43 μM, SI = 10.80). The structureeactivity relationships (SARs) of phenylpropanoid derivatives had been discussed, which were useful for phenylpropanoid derivatives to be explored and developed as novel anti-HBV agents. Moreover, the docking study of all synthesized compounds inside the HLA-A protein (PDB ID: 3OX8) active site were carried out to explore the molecular interactions and a molecular target for activity of phenylpropanoid derivatives with the protein using a moe-docking technique. This study identified a new class of potent anti-HBV agents.
Liu, Sheng,Wei, Wanxing,Li, Yubin,Liu, Xu,Cao, Xiaoji,Lei, Kechan,Zhou, Min
p. 473 - 482
(2015/04/14)

Design, synthesis and cytotoxic evaluation of novel imatinib amide derivatives that target Abl kinase
Novel imatinib amide derivatives (a1-28, b1-9) were synthesized and evaluated for their biological activities. All compounds were characterized by 1H NMR, MS and elemental analysis. Among all the derivatives, compounds a4, a10, a21, b1 and b2 displayed the most significant ability of inhibiting K562 cell proliferation with the IC50 values of 0.67, 0.66, 0.65, 0.59 and 0.62 μM, respectively, indicating that these compounds were potent inhibitors of Bcr-Abl in leukemic K562 cells, comparable to the reference compound imatinib. Molecular docking study was performed to position compounds a21 and b1 into the active site of Abl to determine the probable binding modes
Yao, Ri-Sheng,Guan, Qiu-Xiang,Lu, Xiao-Qin,Ruan, Ban-Feng
p. 20 - 28
(2015/03/31)

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
p. 32 - 41
(2015/05/13)

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents
The cellular antioxidant system plays key roles in blocking or retarding the pathogenesis of adult neurodegenerative disorders as elevated oxidative stress has been implicated in the pathophysiology of such diseases. Molecules with the ability in enhancing the antioxidant defense thus are promising candidates as neuroprotective agents. We reported herein the synthesis of piperlongumine analogues and evaluation of their cytoprotection against hydrogen peroxide- and 6-hydroxydopamine-induced neuronal cell oxidative damage in the neuron-like PC12 cells. The structure-activity relationship was delineated after the cytotoxicity and protection screening. Two compounds (4 and 5) displayed low cytotoxicity and confer potent protection of PC12 cells from the oxidative injury via upregulation of a panel of cellular antioxidant molecules. Genetically silencing the transcription factor Nrf2, a master regulator of the cellular stress responses, suppresses the cytoprotection, indicating the critical involvement of Nrf2 for the cellular action of compounds 4 and 5 in PC12 cells.
Peng, Shoujiao,Zhang, Baoxin,Meng, Xianke,Yao, Juan,Fang, Jianguo
p. 5242 - 5255
(2015/08/03)

Potent and Nontoxic Chemosensitizer of P-Glycoprotein-Mediated Multidrug Resistance in Cancer: Synthesis and Evaluation of Methylated Epigallocatechin, Gallocatechin, and Dihydromyricetin Derivatives
We are interested in developing novel natural product-derived P-gp inhibitors to reverse cancer drug resistance. Here, we have synthesized 55 novel derivatives of methylated epigallocatechin (EGC), gallocatechin (GC), and dihydromyricetin (DHM). Three EGC derivatives (23, 35, and 36) and three GC derivatives (50, 51, and 53) are significantly better than epigallocatechin gallate (EGCG) with a relative fold (RF) ranging from 31.4 to 53.6. The effective concentration (EC50) of 23 and 51 ranges from 102 to 195 nM. Compounds 23 and 51 are noncytotoxic to fibroblasts with IC50 > 100 μM. Compound 23 is specific for P-gp without modulating activity toward MRP1 or BCRP. Compounds 23 and 51 are non-P-gp substrates. Important pharmacophores for P-gp modulation were identified. In summary, methylated EGC and GC derivatives represent a new class of potent, specific, noncytotoxic, and nonsubstrate P-gp modulators.
Wong, Iris L.K.,Wang, Bao-Chao,Yuan, Jian,Duan, Liang-Xing,Liu, Zhen,Liu, Tao,Li, Xue-Min,Hu, Xuesen,Zhang, Xiao-Yu,Jiang, Tao,Wan, Sheng-Biao,Chow, Larry M.C.
p. 4529 - 4549
(2015/06/25)

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)

Tandem superelectrophilic hydroarylation of CC bond and carbonyl reduction in cinnamides: Synthetic rout to 3,3-diarylpropylamines, valuable pharmaceuticals
Cinnamides ArCHCHCONRR′ in reactions with arenes Ar′H under the action of Bronsted (TfOH, FSO3H) or Lewis (AlBr3) superacids at rt for 1-2 h give CC bond hydroarylation products ArAr′CHCH2CONRR′ in yields of 63-98%. Reduction (LiAlH4/Et2O) of carbonyl group in the latter results in the formation of 3,3-diarylpropylamines ArAr′CHCH2CH2NRR′, valuable drugs. The reaction intermediates, superelectrophilic dications ArC+H-CH2C(OH+)NRR′, have been characterized by DFT calculations in terms of global electrophilicity index, natural charges, and atomic orbitals contributions.
Zakusilo, Dmitry N.,Ryabukhin, Dmitry S.,Boyarskaya, Irina A.,Yuzikhin, Oleg S.,Vasilyev, Aleksander V.
p. 102 - 108
(2015/02/02)

Chemical intervention in bacterial lignin degradation pathways: Development of selective inhibitors for intradiol and extradiol catechol dioxygenases
Bacterial lignin degradation could be used to generate aromatic chemicals from the renewable resource lignin, provided that the breakdown pathways can be manipulated. In this study, selective inhibitors of enzymatic steps in bacterial degradation pathways
Sainsbury, Paul D.,Mineyeva, Yelena,Mycroft, Zoe,Bugg, Timothy D.H.
p. 102 - 109
(2015/05/27)

Multifunctional novel Diallyl disulfide (DADS) derivatives with β-amyloid-reducing, cholinergic, antioxidant and metal chelating properties for the treatment of Alzheimer's disease
A series of novel Diallyl disulfide (DADS) derivatives were designed, synthesized and evaluated as chemical agents, which target and modulate multiple facets of Alzheimer's disease (AD). The results showed that the target compounds 5a-l and 7e-m exhibited significant anti-Aβ aggregation activity, considerable acetylcholinesterase (AChE) inhibition, high selectivity towards AChE over butyrylcholinesterase (BuChE), potential antioxidant and metal chelating activities. Specifically, compounds 7k and 7l exhibited highest potency towards self-induced Aβ aggregation (74% and 71.4%, 25 μM) and metal chelating ability. Furthermore, compounds 7k and 7l disaggregated Aβ fibrils generated by Cu2+-induced Aβ aggregation by 80.9% and 78.5%, later confirmed by transmission electron microscope (TEM) analysis. Besides, 7k and 7l had the strongest AChE inhibitory activity with IC50 values of 0.056 μM and 0.121 μM, respectively. Furthermore, molecular modelling studies showed that these compounds were capable of binding simultaneously to catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. All the target compounds displayed moderate to excellent antioxidant activity with ORAC-FL values in the range 0.546-5.86 Trolox equivalents. In addition, absorption, distribution, metabolism and excretion (ADME) profile and toxicity prediction (TOPKAT) of best compounds 7k and 7l revealed that they have drug like properties and possess very low toxic effects. Collectively, the results strongly support our assertion that these compounds could provide good templates for developing new multifunctional agents for AD treatment.
Manral, Apra,Saini, Vikas,Meena, Poonam,Tiwari, Manisha
p. 6389 - 6403
(2015/10/05)

A novel direct synthesis of 3-acyl-4-aryldihydroquinolin-2(1H)-ones via metal-free radical tandem cyclization between N-arylcinnamamides and aldehydes
An efficient metal-free and practical method for the synthesis of disubstituted dihydroquinolin-2(1H)-ones via intermolecular radical tandem addition/cyclization was developed. This method provides a novel and straightforward route to 3-acyl-4-aryldihydro
Mai, Wen-Peng,Wang, Ji-Tao,Xiao, Yong-Mei,Mao, Pu,Lu, Kui
p. 8041 - 8051
(2015/12/31)

A new compd. ferulic acid and raw material and an organic electroluminescence element using the same
PROBLEM TO BE SOLVED: To provide a novel compound using naturally-derived ferulic acid, and an organic electroluminescent element using the novel compound. SOLUTION: The novel compound is represented by general formula wherein A is selected from the group consisting of phenyl, styryl, styrylphenyl, oxadiazole, and benzo[1,2-4,5]bis oxazole; B is selected from the group consisting of cyano, methoxy-alkoxystyryl, benzoxazole derivatives, and coumarin derivatives; and R1is a hydrogen atom, a 1-20C alkyl group, a 1-8C halogen-substituted alkyl group, or a 1-8C acyl group. COPYRIGHT: (C)2013,JPOandINPIT
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Paragraph 0016; 0019

(2018/12/14)

Synthesis and leishmanicidal activity of cinnamic acid esters: Structure-activity relationship
Several cinnamic acid esters were obtained via Fischer esterification of cinnamic acids derivatives with aliphatic alcohols. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes and cytotoxic activity was evaluated against mammalian U-937 cells. The compounds 11, 15-17, and 23, were active against Leishmania parasite and although toxic for mammalian cells, they still are potential candidates for antileishmanial drug development. A SAR analysis indicates that first, while smaller alkyl chains lead to higher selectivity indices (10, 11 vs. 12-17); second, the degree of oxygenation is essential for activity, primarily in positions 3 and 4 (17 vs. 18-20 and 22); and third, hydroxyl groups increase both activity and cytotoxicity (14 vs. 23). On the other hand, the presence of a double bond in the side chain is crucial for cytotoxicity and leishmanicidal activity (12 vs. 21). However, further studies are required to optimize the structure of the promising molecules and to validate the in vitro activity against Leishmania demonstrated here with in vivo studies.
Otero, Elver,Robledo, Sara M.,Diaz, Santiago,Carda, Miguel,Munoz, Diana,Panos, Julian,Velez, Ivan D.,Cardona, Wilson
p. 1378 - 1386
(2014/03/21)

Cinnamic anilides as new mitochondrial permeability transition pore inhibitors endowed with ischemia-reperfusion injury protective effect in vivo
In this account, we report the development of a series of substituted cinnamic anilides that represents a novel class of mitochondrial permeability transition pore (mPTP) inhibitors. Initial class expansion led to the establishment of the basic structural requirements for activity and to the identification of derivatives with inhibitory potency higher than that of the standard inhibitor cyclosporine-A (CsA). These compounds can inhibit mPTP opening in response to several stimuli including calcium overload, oxidative stress, and thiol cross-linkers. The activity of the cinnamic anilide mPTP inhibitors turned out to be additive with that of CsA, suggesting for these inhibitors a molecular target different from cyclophylin-D. In vitro and in vivo data are presented for (E)-3-(4-fluoro-3-hydroxy-phenyl)-N-naphthalen-1-yl- acrylamide 22, one of the most interesting compounds in this series, able to attenuate opening of the mPTP and limit reperfusion injury in a rabbit model of acute myocardial infarction.
Fancelli, Daniele,Abate, Agnese,Amici, Raffaella,Bernardi, Paolo,Ballarini, Marco,Cappa, Anna,Carenzi, Giacomo,Colombo, Andrea,Contursi, Cristina,Di Lisa, Fabio,Dondio, Giulio,Gagliardi, Stefania,Milanesi, Eva,Minucci, Saverio,Pain, Gilles,Pelicci, Pier Giuseppe,Saccani, Alessandra,Storto, Mariangela,Thaler, Florian,Varasi, Mario,Villa, Manuela,Plyte, Simon
supporting information
p. 5333 - 5347
(2014/07/08)

Synthesis and biological evaluation of cinnamido linked benzophenone hybrids as tubulin polymerization inhibitors and apoptosis inducing agents
A new class of hybrid molecules containing cinnamide subunit linked to benzophenone as inhibitors of tubulin polymerization were synthesized and evaluated for their anticancer potential. These hybrids exhibit anticancer activity with IC50 values ranging from 0.06 to 16.3 μM. Compounds 4f and 4g possessing fluoro and trifluoromethyl on the cinnamido subunit showed significant cytotoxic activity with IC50 values 0.06 and 0.09 μM against HeLa cell line, respectively. These compounds showed cell cycle arrest at G2/M phase of the cell cycle and inhibited tubulin polymerization followed by activation of caspase-3 activity and apoptotic cell death. Further in vitro tubulin polymerization assay showed that the level of tubulin inhibition was comparable to that of 2a for the compounds 4f and 4g. Moreover, Hoechst 33258 staining and DNA fragmentation assay suggested that these compounds induce cell death by apoptosis. Overall, the current study demonstrates that the synthesis of benzophenone linked cinnamide subunit conjugates as promising anticancer agents with G2/M arrest and apoptotic-inducing ability via targeting tubulin.
Kamal, Ahmed,Reddy, Ch. Ratna,Vishnuvardhan,Mahesh,Lakshma Nayak,Prabhakar,Reddy, C. Suresh
supporting information
p. 2309 - 2314
(2014/05/20)

An efficient total synthesis of trilepisiumic acid
Total synthesis of trilepisiumic acid (4-((3-(3,4-dihydroxyphenyl)acryloyl) oxy)-3-hydroxybenzoic acid) isolated from Trilepisium madagascariense was carried out. Doebner condensation of 3,4-dimethoxybenzaldehyde with malonic acid yielded 3,4-dimethoxycinnamic acid (2). Esterification of the latter with vanillin afforded 4-formyl-2-methoxyphenyl-3-(3,4-dimethoxy phenyl)acrylate (3) followed by permanganate oxidation in acidic medium provided the corresponding acid 4. Finally, demethylation of 4 was achieved by refluxing in hydrobromic acid to unveil the trilepisiumic acid (1).
Saeed, Aamer,Qasim, Muhammad
supporting information
p. 1121 - 1126
(2014/07/21)

Synthesis and mesomorphic behavior of calamitic liquid crystals with a biphenyl moiety
A new mesogenic homologous series having a biphenyl moiety has been synthesized by condensing 4-hydroxy-4′-nitrobiphenyl- and methoxy-substituted 4-n-alkoxy cinnamoyl chlorides, and their liquid crystalline properties have been studied. All the members of the series are enantiotropic liquid crystals. The methyl to n-pentyl derivatives exhibit both Smectic A (SmA) and Nematic (N) phases; the higher members, starting with the n-hexyl derivative show only a SmA phase. The plot of transition temperatures versus number of carbon atoms in the alkoxy chain exhibits zig-zag pattern for Sm-N and NIsotropic (Iso) transition temperature curves. The average thermal stability is compared with other related homologous series. The introduction of polar nitro group increases significant intermolecular force of attraction which stabilizes the molecular orientation. This results into the increase in the thermal stability of the system.
Tandel,Patel, Nilesh K.
p. 114 - 125
(2014/07/07)

All trans 1-(3-arylacryloyl)-3,5-bis (pyridin-4-ylmethylene)piperidin-4-ones as curcumin-inspired antineoplastics
A series of eleven N-acryloyl/N-cinnamoyl 3,5-bis(pyridin-4-yl)methylene-4-piperidones were synthesized as curcumin-based candidate antineoplastic agents. The cytostatic potency of these compounds was evaluated against three representative cell lines and all compounds were found to exhibit significant anti-cancer cell activity in vitro. QSAR studies using several physicochemical parameters and 50% inhibitory concentration (IC50) values resulted in certain important correlations which will aid design of more potent analogs. Representative test compounds were investigated in the NCI 60-cell line panel where they were found to display a profound cytotoxicity. These compounds were also potent anti-oxidants and inhibitors of human topoisomerase III±. Representative compounds were well-tolerated by human fibroblasts and by mice during the survival/toxicity studies.
Paul, Nawal K.,Jha, Mamta,Bhullar, Khushwant S.,Rupasinghe, H.P. Vasantha,Balzarini, Jan,Jha, Amitabh
p. 461 - 470
(2015/01/09)

Synthesis of mono-, di-, and tri-3,4-dimethoxycinnamoyl-1,5-γ- quinides
Tri-3,4-dimethoxycinnamoyl-1,5-γ-quinide was synthesized and fully characterized by a direct synthesis from quinic acid and a large excess of 3,4-dimethoxycinnamoyl chloride. Mono-and di-3,4-dimethoxycinnamoyl-1,5-γ- quinides were also obtained from the direct coupling of 1,5-γ-quinide and 3,4-dimethoxycinnamoyl chloride in different molar ratios. Moreover, a hypothetical mechanism of the direct lactonization is proposed. Mono-, di-, and tri-3,4-dimethoxycinnamoyl-1,5-γ-quinides have been synthesized from 1,5-γ-quinide and 3,4-dimethoxycinnamoyl chloride in different molar ratios. The only triester quinide was also easily obtained by a direct synthesis from D-(-)-quinic acid in the presence of an excess of the acyl chloride. Copyright
Sinisi, Valentina,Boronova, Katarina,Colomban, Silvia,Navarini, Luciano,Berti, Federico,Forzato, Cristina
p. 1321 - 1326
(2014/03/21)