- 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)
-
- AIE-Active Chiral [3]Rotaxanes with Switchable Circularly Polarized Luminescence
-
The construction of circularly polarized luminescence (CPL) switches with multiple switchable emission states and high dissymmetry factors (glum) has attracted increasing attention due to their broad applications in diverse fields such as the development of smart devices and sensors. Herein, a new family of AIE-active chiral [3]rotaxanes were designed and synthesized, from which a novel CPL switching system was successfully constructed. The switching process was realized through the controlled motions of the chiral pillar[5]arene macrocycles along the axle through the addition or removal of the acetate anions, which not only modulated the chirality information transfer but also tuned the aggregations of the integrated [3]rotaxanes, thus resulting in reversible transformations between two emission states with both high photoluminescence quantum yields (PLQYs) and high dissymmetry factors (glum) values.
- Li, Wei-Jian,Gu, Qingyi,Wang, Xu-Qing,Zhang, Dan-Yang,Wang, Yu-Te,He, Xiao,Wang, Wei,Yang, Hai-Bo
-
supporting information
p. 9507 - 9515
(2021/03/18)
-
- Synthesis and biological evaluation of chalcone-polyamine conjugates as novel vectorized agents in colorectal and prostate cancer chemotherapy
-
The aim of this study was to synthesize chalcone-polyamine conjugates in order to enhance bioavailability and selectivity of chalcone core towards cancer cells, using polyamine-based vectors. Indeed, it is well-known that polyamine transport system is upr
- Barette, Caroline,Champavier, Yves,Liagre, Bertrand,Pinon, Aline,Pouget, Christelle,Rioux, Benjamin,Sol, Vincent,Fagnère, Catherine,Gamond, Aurélie,Laurent, Aurélie,Martin, Frédérique
-
-
- Discovery of Salidroside-Derivated Glycoside Analogues as Novel Angiogenesis Agents to Treat Diabetic Hind Limb Ischemia
-
Therapeutic angiogenesis is a potential therapeutic strategy for hind limb ischemia (HLI); however, currently, there are no small-molecule drugs capable of inducing it at the clinical level. Activating the hypoxia-inducible factor-1 (HIF-1) pathway in skeletal muscle induces the secretion of angiogenic factors and thus is an attractive therapeutic angiogenesis strategy. Using salidroside, a natural glycosidic compound as a lead, we performed a structure-activity relationship (SAR) study for developing a more effective and druggable angiogenesis agent. We found a novel glycoside scaffold compound (C-30) with better efficacy than salidroside in enhancing the accumulation of the HIF-1α protein and stimulating the paracrine functions of skeletal muscle cells. This in turn significantly increased the angiogenic potential of vascular endothelial and smooth muscle cells and, subsequently, induced the formation of mature, functional blood vessels in diabetic and nondiabetic HLI mice. Together, this study offers a novel, promising small-molecule-based therapeutic strategy for treating HLI.
- Han, Jingxuan,He, Yun,Huang, Song,Kasim, Vivi,Liu, Caiping,Marcelina, Olivia,Miyagishi, Makoto,Nugrahaningrum, Dyah Ari,Wang, Guixue,Wu, Shourong,Zou, Meijuan
-
supporting information
(2022/01/14)
-
- Tri-substituted pyrazole derivative and application
-
The invention discloses a tri-substituted pyrazole derivative. Pharmacological research results show that compared with conventional anti-depression medicines, namely fluoxetine and manifarcin, the tri-substituted pyrazole derivative disclosed by the inve
- -
-
Paragraph 0038-0039; 0043-0045
(2020/02/14)
-
- Arylpyrazole compound and application thereof
-
The invention discloses an arylpyrazole compound. The arylpyrazole compound has a structure shown in the description. The arylpyrazole compound has good selective PDE4 inhibition activity and weak PDE4D inhibition effect, and can show more excellent pharm
- -
-
Paragraph 0047; 0051-0053
(2020/06/20)
-
- Synthesis of novel 4-Boc-piperidone chalcones and evaluation of their cytotoxic activity against highly-metastatic cancer cells
-
In this study, six curcuminoids containing a tert-butoxycarbonyl (Boc) piperidone core were successfully synthesized, five of them are novel compounds reported here for the first time. These compounds were prepared through an aldolic condensation by adding tetrahydropyranyl-protected benzaldehydes or substituted benzaldehyde to a reaction mixture containing 4-Boc-piperidone and lithium hydroxide in an alcoholic solvent. A 44–94% yield was obtained supporting the developed methodology as a good strategy for the synthesis of 4-Boc-piperidone chalcones. Cytotoxic activity against LoVo and COLO 205 human colorectal cell lines was observed at GI50 values that range from 0.84 to 34.7 μg/mL, while in PC3 and 22RV1 human prostate cancer cell lines, GI50 values ranging from 17.1 to 22.9 μg/mL were obtained. Results from biochemical assays suggest that the cytotoxicity of the 4-Boc-piperidone chalcones can be linked to their ability to induce apoptosis, decrease the activity of NFκB and cellular proliferation. Our findings strongly support the potential of Boc-piperidone chalcones as novel cytotoxic agents against highly-metastatic cancer cells.
- Ocasio-Malavé, Carlimar,Donate, Metsiel J.,Sánchez, María M.,Sosa-Rivera, Jesús M.,Mooney, Joseph W.,Pereles-De León, Tomás A.,Carballeira, Néstor M.,Zayas, Beatriz,Vélez-Gerena, Christian E.,Martínez-Ferrer, Magaly,Sanabria-Ríos, David J.
-
supporting information
(2019/11/29)
-
- Hydroquinone and benzoquinone-catalyzed aqueous Knoevenagel condensation
-
A Knoevenagel condensation of various aldehydes with malononitrile effectively proceeded in the presence of hydroquinone/benzoquinone mixed catalysts at room temperature in H2O. Furthermore, γ-deuterium-labeled α,β-unsaturated nitrile derivatives were als
- Koyama, Kaho,Kuwata, Marina,Sajiki, Hironao,Sawama, Yoshinari,Takakura, Ryoya,Yamada, Tsuyoshi
-
supporting information
p. 6594 - 6597
(2020/09/21)
-
- Inhibitory effects of N-(acryloyl)benzamide derivatives on tyrosinase and melanogenesis
-
Targeting of tyrosinase has proven to be the best means of identifying safe, efficacious, and potent tyrosinase inhibitors for whitening skin. We designed and synthesized ten NAB (N-(acryloyl)benzamide) derivatives (1a–1j) using the Horner-Wadsworth-Emmon
- Lee, Sanggwon,Ullah, Sultan,Park, Chaeun,Won Lee, Hee,Kang, Dongwan,Yang, Jungho,Akter,Park,Chun, Pusoon,Moon, Hyung Ryong
-
p. 3929 - 3937
(2019/07/30)
-
- Design, synthesis and identification of novel coumaperine derivatives for inhibition of human 5-LOX: Antioxidant, pseudoperoxidase and docking studies
-
5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors especially, natural product based ones, are highly attractive. Coumaperine, a natural product found in white pepper and its derivatives were herein developed as 5-LOX inhibitors. We have synthesized twenty four derivatives, characterized and evaluated their 5-LOX inhibition potential. Coumaperine derivatives substituted with multiple hydroxy and multiple methoxy groups exhibited best 5-LOX inhibition. CP-209, a catechol type dihydroxyl derivative and CP-262-F2, a vicinal trihydroxyl derivative exhibited, 82.7% and 82.5% inhibition of 5-LOX respectively at 20 μM. Their IC50 values are 2.1 ± 0.2 μM and 2.3 ± 0.2 μM respectively, and are comparable to zileuton, IC50 = 1.4 ± 0.2 μM. CP-155, a methylenedioxy derivative (a natural product) and CP-194, a 2,4,6-trimethoxy derivative showed 76.0% and 77.1% inhibition of 5-LOX respectively at 20 μM. Antioxidant study revealed that CP-209 and 262-F2 (at 20 μM) scavenged DPPH radical by 76.8% and 71.3% respectively. On the other hand, CP-155 and 194 showed very poor DPPH radical scavenging activity. Pseudo peroxidase assay confirmed that the mode of action of CP-209 and 262-F2 were by redox process, similar to zileuton, affecting the oxidation state of the metal ion in the enzyme. On the contrary, CP-155 and 194 probably act through some other mechanism which does not involve the disruption of the oxidation state of the metal in the enzyme. Molecular docking of CP-155 and 194 to the active site of 5-LOX and binding energy calculation suggested that they are non-competitive inhibitors. The In-Silico ADME/TOX analysis shows the active compounds (CP-155, 194, 209 and 262-F2) are with good drug likeliness and reduced toxicity compared to existing drug. These studies indicate that there is a great potential for coumaperine derivatives to be developed as anti-inflammatory drug.
- Muthuraman, Subramani,Sinha, Shweta,Vasavi,Waidha, Kamran Manzoor,Basu, Biswarup,Munussami, Punnagai,Balamurali,Doble, Mukesh,Saravana Kumar, Rajendran
-
supporting information
p. 604 - 619
(2019/01/14)
-
- Synthesis and evaluation of aryliden- and hetarylidenfuranone derivatives of usnic acid as highly potent Tdp1 inhibitors
-
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a repair enzyme for stalled DNA-topoisomerase 1 (Top 1) cleavage complexes and other 3′-end DNA lesions. Tdp1 is a promising target for anticancer therapy, since it can repair DNA lesions caused by Top1 inhibitors leading to drug resistance. Hence, Tdp1 inhibition should result in synergistic effect with Top1 inhibitors. Twenty nine derivatives of (+)-usnic acid were tested for in vitro Tdp1 inhibitory activity using a fluorescent-based assay. Excellent activity was obtained, with derivative 6m demonstrating the lowest IC50 value of 25 nM. The established efficacy was verified using a gel-based assay, which gave close results to that of the fluorescent assay. In addition, molecular modeling in the Tdp1 substrate binding pocket suggested plausible binding modes for the active analogues. The synergistic effect of the Tdp1 inhibitors with topotecan, a Top1 poison in clinical use, was tested in two human cell lines, A-549 and HEK-293. Compounds 6k and 6x gave very promising results. In particular, 6x has a low cytotoxicity and an IC50 value of 63 nM, making it a valuable lead compound for the development of potent Tdp1 inhibitors for clinical use.
- Zakharova, Olga,Luzina, Olga,Zakharenko, Alexandra,Sokolov, Dmitry,Filimonov, Alexandr,Dyrkheeva, Nadezhda,Chepanova, Arina,Ilina, Ekaterina,Ilyina, Anna,Klabenkova, Kristina,Chelobanov, Boris,Stetsenko, Dmitry,Zafar, Ayesha,Eurtivong, Chatchakorn,Reynisson, Jóhannes,Volcho, Konstantin,Salakhutdinov, Nariman,Lavrik, Olga
-
supporting information
p. 4470 - 4480
(2018/08/03)
-
- Compound Cur20 and preparing method and application thereof
-
The invention discloses a novel compound Cur20 and a preparing method thereof. The structural formula of the novel compound is shown in the description. The compound Cur20 has the antioxidation effect, can promote generation of blood vessels, and can be u
- -
-
Paragraph 0027; 0031; 0032
(2018/06/16)
-
- Synthesis of coumaperine derivatives: Their NF-κB inhibitory effect, inhibition of cell migration and their cytotoxic activity
-
Coumaperine (an amide alkaloid, present in white piper) and its derivatives were synthesized and investigated for their cytotoxicity against L428 and A549 cells and their NF-κB inhibitory activity. It was found that the coumaperine derivatives CP-9 and CP-38 suppress NF-κB subunits p50 and p65 in nuclear fractions by western blot and by NF-κB luciferase reporter gene assay in a dose dependent manner. Confirmation of these results was obtained by confocal microscopy. CP-9, CP-32 and CP-38 also exhibited dose dependent cell cytotoxicity in a L428?cells expressing constitutively active NF-κB and in A549?cells, with an IC50 value of 43.25?μg/ml, 0.39?μg/ml and 16.85?μg/ml respectively against L428?cells and 57.15?μg/ml, 69.1?μg/ml and 63.2?μg/ml respectively against A549?cells. In addition, the coumaperine derivatives show remarkable inhibitory activity on the cancer cell migration assay against A549 lung adenocarcinoma cells at the concentrations of 5?μg/ml, 10?μg/ml, and 5?μg/ml of CP-9, CP-32 and CP-38 respectively. Aromatic substituents and number of olefinic double bond in coumaperine derivatives found to influence the inhibitory activity. In luciferase reporter gene assay, di-olefin conjugated coumaperine derivatives, CP-38, CP-32 and PIP exhibited higher inhibitory activity than their corresponding tri-olefin conjugated coumaperine derivatives, CP-102, CP-146 and PIP-155 respectively. CP-32 with a stronger electron donating group (-N(CH3)2) showed better inhibitory activity in luciferase reporter gene assay and in cell proliferation of L428?cells. Simple coumaperine derivative (CP-9, with no substituent) effectively inhibited A549?cells proliferation and migration than the other coumaperine derivatives. CP-9 and CP-38 diminish significantly the NF-κB subunits (p50 and p65) of L428?cells in nuclear fractions at the dosage of 10?μg/ml and 30?μg/ml respectively. Which clearly shows that CP-9 and CP-38 inactivate the NF-κB pathway in?vitro.
- Nandakumar, Natarajan,Muthuraman, Subramani,Gopinath, Pushparathinam,Nithya, Pattusamy,Gopas, Jacob,Kumar, Rajendran Saravana
-
supporting information
p. 1076 - 1087
(2016/11/09)
-
- Selective hydrogenation of conjugated unsaturated ketones containing a hydroxyaryl substituent in the β-position
-
A high selectivity was achieved in the Ni2B-catalyzed hydrogenation of α,β-unsaturated ketones containing a hydroxyaryl (phenolic) substituent in the β-position. The developed hydrogenation procedure was used to synthesize natural compounds of the phenylpropane series and their structural analogs.
- Kovalenko,Pratsko
-
-
- Hydroxy-substituted trans-cinnamoyl derivatives as multifunctional tools in the context of Alzheimer's disease
-
Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. In recent years, a plethora of proteins and biochemical pathways has been proposed as possible targets to counteract neurotoxicity. Although the complex scenario is not completely elucidated, close relationships are emerging among some of these actors. In particular, increasing evidence has shown that aggregation of amyloid beta (Aβ), glycogen synthase kinase 3β (GSK-3β) and oxidative stress are strictly interconnected and their concomitant modulation may have a positive and synergic effect in contrasting AD-related impairments. We designed compound 3 which demonstrated the ability to inhibit both GSK-3β (IC50 = 24.36 ± 0.01 μM) and Aβ42 self-aggregation (IC50 = 9.0 ± 1.4 μM), to chelate copper (II) and to act as exceptionally strong radical scavenger (kinh = 6.8 ± 0.5 · 105 M?1s?1) even in phosphate buffer at pH 7.4 (kinh = 3.2 ± 0.5 · 105 M?1s?1). Importantly, compound 3 showed high-predicted blood-brain barrier permeability, did not exert any significant cytotoxic effects in immature cortical neurons up to 50 μM and showed neuroprotective properties at micromolar concentration against toxic insult induced by glutamate.
- De Simone, Angela,Bartolini, Manuela,Baschieri, Andrea,Apperley, Kim Y.P.,Chen, Huan Huan,Guardigni, Melissa,Montanari, Serena,Kobrlova, Tereza,Soukup, Ondrej,Valgimigli, Luca,Andrisano, Vincenza,Keillor, Jeffrey W.,Basso, Manuela,Milelli, Andrea
-
p. 378 - 389
(2017/08/21)
-
- Synthesis, structure, and antioxidant activity of methoxy- and hydroxyl-substituted 2'-aminochalcones
-
Abstract: Three 2'-aminochalcone derivatives (E)-1-(2-aminophenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one, (E)-1-(2-aminophenyl)-3-(3,4-dihydroxyphenyl)prop-2-en-1-one, and (E)-1-(2-amino-4,5-dimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one, have been synthesized, characterized, and tested in vitro in order to assess their antioxidant activity. All compounds were characterized on the basis of 1H NMR, 13C NMR, ESI-mass spectrometry, FT-IR, UV/Vis, and elemental analysis. The X-ray crystal structures of (E)-1-(2-aminophenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one and (E)-1-(2-amino-4,5-dimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one were successfully determined showing a planar molecule geometry. Studies on the biological properties including test of free radical scavenging ability (DPPH test)?and superoxide dismutase mimetic activity were performed. The results indicate that the aminochalcone carrying two hydroxyl functionalities in adjacent meta and para position exhibits a stronger antioxidant activity than the other derivatives. Graphical abstract: [Figure not available: see fulltext.]
- Sulpizio, Chiara,Roller, Alexander,Giester, Gerald,Rompel, Annette
-
p. 1747 - 1757
(2016/09/28)
-
- Synthesis, characterization, and antioxidant activity of Zn2+ and Cu2+ coordinated polyhydroxychalcone complexes
-
Four new metal complexes [Cu(ISO)2], [Cu(BUT)2] and [Zn(ISO)2], [Zn(BUT)2] of the polyhydroxychalcones (isoliquiritigenin and butein) are synthesized, structurally characterized and their antioxidant activity is investigated. The formation of the complexes [Cu(ISO)2] and [Zn(ISO)2] is followed by Job’s plot using NMR titration. The resulting compounds are characterized by mass spectrometry, IR spectroscopy, and elemental analysis. Studies on the radical scavenging activity are performed using DPPH as substrate. The results showed that the antioxidant activities of isoliquiritigenin and butein are enhanced after binding to copper or zinc. Graphical abstract: [Figure not available: see fulltext.]
- Sulpizio, Chiara,Müller, Simon T. R.,Zhang, Qi,Brecker, Lothar,Rompel, Annette
-
p. 1871 - 1881
(2016/10/22)
-
- Isoglycyrrhiza derivatives and its use (by machine translation)
-
The invention discloses a different of glycyrrhizin derivatives and their use, the structure of the isoliquiritigenin main body: wherein R 1 is H, methyl, cyclopropane methyl, 3-methyl-2-butenyl, is d acyl, alkyl in the isobutene, R 2 is H, methyl, cyclopropane methyl, 3-methyl-2-butenyl, is d acyl, alkyl of isobutene. Said compound can be used for the treatment of atrial fibrillation, and is capable of effectively inhibiting potassium channel function of the patient and small side effect. (by machine translation)
- -
-
Paragraph 0039; 0041; 0042
(2017/05/20)
-
- CYCLIC OLEFIN COMPOUND, PHOTOREACTIVE POLYMER AND ALIGNMENT LAYER COMPRISING THE SAME
-
The present invention relates to: a cyclic olefin compound which exhibits excellent liquid crystal alignment properties and alignment speed, has a characteristic that the alignment direction can easily be varied depending on the polarization direction, an
- -
-
Paragraph 0216; 0217
(2016/12/12)
-
- New chalcones containing nucleosides exhibiting in vitro anti-cancer activities
-
Twenty-one new chalcones 9a-m (excluding 9e, 9j and 9l) and 10a-m (excluding 10j and 10l), containing nucleobases were synthesized from 2'-hydroxyacetophenone (1) by the reactions including chloromethylation, nucleophilic substitution with thymine and uracil, and Claisen-Schmidt reactions. These new chalcones were evaluated for in vitro cytotoxicity against five human cancer cell lines: SK-LU-1, Hep-G2, MCF7, SW480 and P388. The results showed that most of the tested chalcones exhibited inhibitory activity against five cancer cell lines except 10h, and 10i. Among the synthesized chalcones, compound 10c exhibited most potent cytotoxicity against MCF-7, SK-LU-1, SW480, HepG2 and P388 with IC50 values of 4.42, 4.81, 5.27, 3.67 and 4.11μg/mL, respectively.
- Van Chinh, Luu,Hung, Truong Ngoc,Nga, Nguyen Thi,Phong, Le,Huong, Le Mai,Ha, Tran Thi Hong,Kim, Soo Un,Vu, Tran Khac
-
p. 534 - 545
(2014/05/20)
-
- Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: Synthesis, biological activity, crystal structure, and in silico evaluation
-
The discovery of potent inhibitors of prostaglandin E2 (PGE 2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a
- Rullah, Kamal,Mohd Aluwi, Mohd Fadhlizil Fasihi,Yamin, Bohari M.,Abdul Bahari, Mohd Nazri,Wei, Leong Sze,Ahmad, Syahida,Abas, Faridah,Ismail, Nor Hadiani,Jantan, Ibrahim,Wai, Lam Kok
-
supporting information
p. 3826 - 3834
(2014/09/16)
-
- Synthesis, cytotoxicity against human oral cancer KB cells and structure-activity relationship studies of trienone analogues of curcuminoids
-
A general method for the synthesis of substituted (1E,4E,6E)-1,7- diphenylhepta-1,4,6-trien-3-ones, based on the aldol condensations of substituted 4-phenylbut-3-en-2-ones and substituted 3-phenylacrylaldehydes, was achieved. The natural trienones 4 and 5 have been synthesized by this method, together with the trienone analogues 9-20. These analogues were evaluated for their cytotoxic activity against human oral cancer KB cell line. The structure-activity relationship study has indicated that the analogues with the 1,4,6-trien-3-one function are more potent than the curcuminoid-type function. Analogues with meta-oxygen function on the aromatic rings are more potent than those in the ortho- and para-positions. Free phenolic hydroxy group is more potent than the corresponding methyl ether analogues. Among the potent trienones, compounds 11, 18 and 20 were more active than the anticancer drug ellipticine. All compounds were also evaluated against the non-cancerous Vero cells and it was found that compounds 11, 12 and 17 were much less toxic than curcumin (1); they showed high selectivity indices of 35.46, 33.46 and 31.68, respectively. These analogues are regarded as the potent trienones for anti-oral cancer study.
- Chuprajob, Thipphawan,Changtam, Chatchawan,Chokchaisiri, Ratchanaporn,Chunglok, Warangkana,Sornkaew, Nilubon,Suksamrarn, Apichart
-
supporting information
p. 2839 - 2844
(2014/06/10)
-
- Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway
-
Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/β-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of β-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of β-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than 1a (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma.
- Leow, Pay-Chin,Bahety, Priti,Boon, Choon Pei,Lee, Chong Yew,Tan, Kheng Lin,Yang, Tianming,Ee, Pui-Lai Rachel
-
-
- Synthesis and anti-tumor activity of novel aminomethylated derivatives of isoliquiritigenin
-
A series of new aminomethylated derivatives of isoliquiritigenin was synthesized. The structures of the compounds were confirmed by IR, MS, NMR, 13C-NMR and elemental analyses. Cytotoxic activities of these derivatives towards the human prostatic cell line PC-3, human mammary cancer cell line MCF-7 and human oophoroma cell line HO-8910 in vitro were tested. The IC50 values showed cytotoxic activities of some of these new derivatives were relatively strong. Furthermore, tumor growth inhibition in vivo of aminomethylated derivatives of isoliquiritigenin 15 was superior to that of isoliquritigenin and reached inhibition rates of 71.68%. The detailed synthesis, spectroscopic data, biological and pharmacologicalactivities of the synthesized compounds were provided.
- Fu, Haoran,Zhang, Yuhang,Wang, Xiqing,Han, Yingzhi,Peng, Xiao,Efferth, Thomas,Fu, Yujie
-
p. 17715 - 17726
(2015/03/04)
-
- 1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as orally bioavailable transcriptional function suppressors of Estrogen-related receptor α
-
Estrogen-related receptor α is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure-activity relationship study of a series of 1-phenyl-4-benzoyl-1H-1,2, 3-triazoles as novel suppressors of ERRα
- Xu, Shilin,Zhuang, Xiaoxi,Pan, Xiaofen,Zhang, Zhang,Duan, Lei,Liu, Yingxue,Zhang, Lianwen,Ren, Xiaomei,Ding, Ke
-
p. 4631 - 4640
(2013/07/19)
-
- A scalable process for the synthesis of (E)-pterostilbene involving aqueous Wittig olefination chemistry
-
A synthetic approach toward the pharmacologically active (E)-stilbene pterostilbene is described using a Wittig reaction conducted under mildly basic, aqueous conditions. A surprising, non-intuitive difference in (E)/(Z) stereoselectivity was observed comparing the two possible isomeric Wittig routes, allowing for the development of a highly efficient process to access the title stilbene derivative through a one-pot olefination deprotection sequence.
- McNulty, James,McLeod, David
-
supporting information
p. 6303 - 6306
(2013/11/06)
-
- Synthesis of pterostilbene by julia olefination
-
A simple, E-stereoselective route for the synthesis of the biologically active compounds trans-pterostilbene and tetramethoxy stilbene from the readily available starting materials 3,5-dimethoxy benzyl alcohol and 4-hydroxy benzaldehyde was developed using Julia olefination as a key reaction. Taylor & Francis Group, LLC.
- Peddikotla, Prabhakar,Chittiboyina, Amar G.,Khan, Ikhlas A.
-
p. 3217 - 3223
(2014/01/06)
-
- Long conjugated 2-nitrobenzyl derivative caged anticancer prodrugs with visible light regulated release: Preparation and functionalizations
-
A series of anticancer prodrugs with different chemical functional groups were prepared, in which the styryl conjugated 2-nitrobenzyl derivatives were introduced as the phototrigger to regulate the drug (chlorambucil) release. Compared to the common 4,5-dimethoxy-2-nitrobenzyl caged compounds, most of the prodrugs exhibited large and redshifted one-photon absorption within the visible range. One-photon excitation for the drug release was studied by measuring UV-vis absorption, FT-IR, and HPLC spectra, which suggested that chlorambucil was released effectively and precisely by manipulating external light conditions. And the introduction of different functional groups made this type of prodrug a good platform to further react with some typical drug carriers and to further form excellent visible light responsive drug delivery systems. Moreover, the drug also could be effectively released under the excitation of two-photon at 800 nm with comparable photorelease efficiencies. The Royal Society of Chemistry 2012.
- Bao, Chunyan,Jin, Ming,Li, Bo,Xu, Yaodong,Jin, Jingyan,Zhu, Linyong
-
supporting information; experimental part
p. 5238 - 5244
(2012/08/08)
-
- Synthesis and QSAR analysis of chalcone derivatives as nitric oxide inhibitory agent
-
In this study, thirty-eight chalcone analogs were synthesized and evaluated for nitric oxide (NO) inhibition activity on RAW 264.7 cells. Among these compounds, chalcones bearing furanyl group showed remarkable anti-inflammatory activity. Both compounds 2d and 2j were identified as the most potent NO inhibitor on IFN-γ/LPS-activated RAW 264.7 cells. In order to examine the structure-activity relationship, a 3D QSAR analysis was carried out by comparative molecular field analysis (CoMFA) method on the selected chalcones. Partial least square analysis produced a statistically coherent model with good predictive value, r2 = 0.989 and a good cross validated value, q 2 = 0.583.
- Lam, Kok Wai,Lajis, Nordin H.,Uddin, Reaz,Ul-Haq, Zaheer,Liew, Choi Yi,Tham, Chau Ling,Israf, Daud A.,Syahida, Ahmad,Rahman, Mohd. Basyaruddin Abdul
-
p. 1953 - 1966,14
(2020/07/30)
-
- Multitarget-directed benzylideneindanone derivatives: Anti-β-amyloid (Aβ) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer's disease
-
A novel series of benzylideneindanone derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. The in vitro studies showed that most of the molecules exhibited a significant ability to inhibit self-induced β-amyloid (Aβ 1-42) aggregation (10.5-80.1%, 20 μM) and MAO-B activity (IC 50 of 7.5-40.5 μM), to act as potential antioxidants (ORAC-FL value of 2.75-9.37), and to function as metal chelators. In particular, compound 41 had the greatest ability to inhibit Aβ1-42 aggregation (80.1%), and MAO-B (IC50 = 7.5 μM) was also an excellent antioxidant and metal chelator. Moreover, it is capable of inhibiting Cu(II)-induced Aβ1-42 aggregation and disassembling the well-structured Aβ fibrils. These results indicated that compound 41 is an excellent multifunctional agent for the treatment of AD.
- Huang, Ling,Lu, Chuanjun,Sun, Yang,Mao, Fei,Luo, Zonghua,Su, Tao,Jiang, Huailei,Shan, Wenjun,Li, Xingshu
-
p. 8483 - 8492,10
(2020/09/15)
-
- Combination of NH2OH·HCl and NaIO4: A new and mild oxidizing agent for selective oxidation of alcohols to carbonyl compounds
-
A new method for oxidation of alcohols to carbonyl compounds has been developed using NH2OH·HCl and NaIO4 under mild reaction conditions at room temperature. Application of the method for the synthesis of diiodo compound from α,β-unsaturated carbonyl compound is also described.
- Majee, Adinath,Kundu, Shrishnu Kumar,Santra, Sougata,Hajra, Alakananda
-
experimental part
p. 4433 - 4435
(2012/09/25)
-
- Anhydrous FePO4 as a cost-effective and recyclable catalyst for tetrahydropyranylation and tetrahydrofuranylation of alcohols and phenols
-
In this article, a mild and efficient protocol for the tetrahydropyranylation and tetrahydrofuranylation of various aliphatic and benzylic alcohols and phenols into their corresponding THP and THF ethers (with 3,4-dihydro- 2H-pyran, DHP and 2,3-dihydrofuran, DHF) has been developed using a catalytic amount of anhydrous FePO4 at room temperature and relatively short reaction times in good to excellent yields.
- Behbahani, Farahnaz K.,Farahani, Mona
-
experimental part
p. 431 - 435
(2012/04/17)
-
- Total synthesis of 3′,3?-binaringenin and related biflavonoids
-
The synthesis of natural 3++,3?-binaringenin and four related biflavonoids was performed in good overall yield (15-35%) starting from readily available phloroglucinol and 4-hydroxy- or 4-methoxybenzaldehyde. Preliminary results indicate that some of these compounds have an interesting activity against S. aureus. Georg Thieme Verlag Stuttgart.
- Sagrera, Gabriel,Seoane, Gustavo
-
supporting information; experimental part
p. 2776 - 2786
(2010/10/19)
-
- POLYMERIZABLE LIQUID CRYSTAL COMPOUND, POLYMERIZABLE LIQUID CRYSTAL COMPOSITION, LIQUID CRYSTALLINE POLYMER, AND OPTICALLY ANISOTROPIC MATERIAL
-
A polymerizable liquid crystal compound shown by the following formula (I), a polymerizable liquid crystal composition that includes the polymerizable liquid crystal compound and a chiral compound polymerizable with the polymerizable liquid crystal compou
- -
-
Page/Page column 35
(2010/01/29)
-
- Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR
-
The chemopreventive potential of functionalized aurones and related compounds as inducers of NAD(P)H:quinone oxidoreductase 1 (NQO1, EC 1.6.99.2) are described. Several 4,6-dimethoxy and 5-hydroxyaurones induced NQO1 activity of Hepa1c1c7 cells by 2-fold at submicromolar concentrations, making these the most potent inducers to be identified from this class. Mechanistically, induction of NQO1 was mediated by the activation of AhR/XRE and Nrf2/ARE pathways, indicating that aurones may be mixed activators of NQO1 induction or agents capable of exploiting the proposed cross-talk between the AhR and Nrf2 gene batteries. QSAR analysis by partial least squares projection to latent structures (PLS) identified size parameters, in particular those associated with non-polar surface areas, as an important determinant of induction activity. These were largely determined by the substitution on rings A and B. A stereoelectronic role for the exocyclic double bond as reflected in the E LUMO term was also identified. The electrophilicity of the double bond or its effect on the conformation of the target compound are possible key features for induction activity.
- Lee, Chong-Yew,Chew, Eng-Hui,Go, Mei-Lin
-
experimental part
p. 2957 - 2971
(2010/09/03)
-
- Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues
-
Curcuminoids have been reported to possess multifunctional bioactivities, especially the ability to inhibit proinflammatory induction. Since it has been suggested that the seven-carbon β-diketone linker in curcumin is responsible for its instability, nine mono-carbonyl five-carbon linker containing analogues were designed and synthesized. Their bioactivity against lipopolysaccharide-induced TNF-α amd IL-6 secretion was evaluated by using mouse J774.1 macrophages. The results showed that the 3′-methoxyl plays an important role in bioactivity and cyclohexanone containing analogues exhibited stronger inflammatory inhibition than acetone and cyclopentanone analogues. Subsequently the most active analogue 3c was determined using single-crystal X-ray diffraction. X-ray analysis and comparison with curcumin reveals that the presence of cyclohexanone in 3c, which remotely resembles the 6-membered ring in the enol tautomer in curcumin, may play an important role in the bioactivity. It is suggested that five-carbon linker analogues containing a cyclohexane ring which are synthetically assessable may be pharmacologically important.
- Liang, Guang,Yang, Shulin,Zhou, Huiping,Shao, Lili,Huang, Kexin,Xiao, Jian,Huang, Zhifeng,Li, Xiaokun
-
experimental part
p. 915 - 919
(2009/09/08)
-
- Anomalous photophysics of bis(hydroxystyryl)benzenes: A twist on the para/meta dichotomy
-
(Chemical Equation Presented) The dianions of two isomeric bis(hydroxystyryl)benzenes show dramatically different photophysical properties.
- Solntsev, Kyril M.,McGrier, Psaras L.,Fahrni, Christoph J.,Tolbert, Laren M.,Bunz, Uwe H. F.
-
supporting information; experimental part
p. 2429 - 2432
(2009/05/26)
-
- New 7,8-benzoflavanones as potent aromatase inhibitors: Synthesis and biological evaluation
-
Some natural compounds such as flavonoids are known to possess a moderate inhibitory activity against aromatase, this enzyme being an interesting target for hormone-dependent breast cancer treatment. It has been demonstrated that the modulation of flavonoid skeleton could increase anti-aromatase effect. Therefore, new 7,8-benzoflavanones were synthesized and tested for their activity toward aromatase inhibition. It was observed that the introduction of a benzo ring at position C-7 and C-8 on flavanone skeleton led to new potent aromatase inhibitors, the resulting 7,8-benzoflavanones being until nine times more potent than aminogluthetimide (the first aromatase inhibitor used clinically).
- Yahiaoui, Samir,Fagnere, Catherine,Pouget, Christelle,Buxeraud, Jacques,Chulia, Albert-Jose
-
p. 1474 - 1480
(2008/09/19)
-
- Synthesis and anti-bacterial properties of mono-carbonyl analogues of curcumin
-
The synthesis of three series of curcumin analogues with mono-carbonyl is described. Their in vitro antibacterial activities against seven Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the aryl ring and the space structure of the linking strain were discussed. It was observed that part of the derivatives displayed significant activity when compared with curcumin and most of them exhibited activity against the ampicillin-resisted Enterobacter cloacae. Compounds A12, B09, B13, B14 and C09 show remarkable antibacterial activity in vitro. The result showed that heterocycle or long-chain substituents may enhance the activity of curcumin analogues.
- Liang, Guang,Yang, Shulin,Jiang, Lijuan,Zhao, Yu,Shao, Lili,Xiao, Jian,Ye, Faqing,Li, Yueru,Li, Xiaokun
-
p. 162 - 167
(2008/09/19)
-
- Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin
-
Curcumin has been extensively studied for its anti-inflammatory activities. However, its potential beneficial effects on various disease preventions and treatments are limited by its unstable structure. The β-diketone moiety renders curcumin to be rapidly metabolized by aldo-keto reductase in liver. In the present study, a series of curcumin analogues with more stable chemical structures were synthesized and several compounds showed an enhanced ability to inhibit lipopolysaccharide (LPS)-induced TNF-α and IL-6 synthesis in macrophages.
- Liang, Guang,Li, Xiaokun,Chen, Li,Yang, Shulin,Wu, Xudong,Studer, Elaine,Gurley, Emily,Hylemon, Phillip B.,Ye, Faqing,Li, Yueru,Zhou, Huiping
-
p. 1525 - 1529
(2008/09/19)
-
- Dimethoxyaurones: Potent inhibitors of ABCG2 (breast cancer resistance protein)
-
A series of 4,6-dimethoxyaurones were synthesized by reacting 4,6-dimethoxybenzofuran-3(2H)-one with various benzaldehydes in a base-catalyzed aldol reaction. A Z configuration was assigned to the aurones based on spectroscopic and crystallographic data.
- Sim, Hong-May,Lee, Chong-Yew,Ee, Pui Lai Rachel,Go, Mei-Lin
-
p. 293 - 306
(2008/12/23)
-
- Hydroxy-cruciforms
-
The synthesis of hydroxy-cruciforms 7 and 8 and their dramatically varying photophysical properties upon exposure to amines are reported. The Royal Society of Chemistry.
- McGrier, Psaras L.,Solntsev, Kyril M.,Sch?nhaber, Jan,Brombosz, Scott M.,Tolbert, Laren M.,Bunz, Uwe H. F.
-
p. 2127 - 2129
(2008/02/08)
-
- Acid catalyzed stereoselective rearrangement and dimerization of flavenes: synthesis of dependensin
-
Appropriately substituted flavenes undergo stereoselective rearrangement and dimerization when treated with methanolic hydrochloric acid to give benzopyranobenzopyrans. A rationale for the rearrangement is proposed. This synthetic methodology has been used for a high yield synthesis of the natural product dependensin.
- Deodhar, Mandar,Black, David StC,Kumar, Naresh
-
p. 5227 - 5235
(2008/02/01)
-
- A METHACRYLATE-BOUND PHOTOISOMERIZABLE CHROMOPHORE, METHODS FOR ITS SYNTHESIS AND OF ITS INTERMEDIATES
-
The invention discloses novel dicyanostilbene derivatives bound to a methacrylic moiety that can serve as an active chromophore in a 3-dimensional optical memory, processes for its synthesis and its intermediates.
- -
-
Page/Page column 24-25
(2008/06/13)
-
- Chemotherapy of leishmaniasis part II: Synthesis and bioevaluation of substituted arylketene dithioacetals as antileishmanial agents
-
Some novel aryl substituted ketene dithioacetals 6 (a-d), 9 (a-c) and 10 (a-c) have been synthesized using novel synthetic methods. The compounds were screened against Leishmania donovani in hamsters for their activity profile. Some of the compounds inhibited 50-65% parasite growth at 50mg kg-1 × 5 days.
- Pandey, Susmita,Suryawanshi,Gupta, Suman,Srivastava
-
p. 751 - 756
(2007/10/03)
-
- A highly efficient synthetic protocol for tetrahydropyranylation/ depyranylation of alcohols and phenols
-
Bismuth(III) nitrate pentahydrate [Bi(NO3)3· 5H2O] is found to be an effective catalyst for both tetrahydropyranylation and depyranylation of alcohols and phenols. Some of the major advantages of this protocol are: non-aqueous workup, good yields, the involvement of a less-expensive and nontoxic catalyst, and compatibility in the presence of a large number of other protecting groups. Notably, isopropylidene, benzylidene, and thioacetal groups are also unaffected under the experimental conditions. Remarkably, a selective mono-protection of diols and primary alcohols can be achieved chemoselectively by employing the same catalyst. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
- Khan, Abu T.,Ghosh, Subrata,Choudhury, Lokman H.
-
p. 4891 - 4896
(2007/10/03)
-
- Novel tetralone-derived retinoic acid metabolism blocking agents: Synthesis and in vitro evaluation with liver microsomal and MCF-7 CYP26A1 cell assays
-
The potent inhibitory activity of novel 2-benzyltetralone and 2-benzylidenetetralone derivatives vs liver microsomal retinoic acid metabolizing enzymes and a MCF-7 CYP26A1 cell assay is described. In the liver microsomal assay, the 2-biphenylmethyl-6-hydr
- Yee, Sook Wah,Jarno, Laetitia,Gomaa, Mohamed Sayed,Elford, Carole,Ooi, Li-Ling,Coogan, Michael P.,McClelland, Richard,Nicholson, Robert Ian,Evans, Bronwen A. J.,Brancale, Andrea,Simons, Claire
-
p. 7123 - 7131
(2007/10/03)
-
- Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents
-
In an effort to develop potent anti-inflammatory and cancer chemopreventive agents, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde or prepared with appropriate dihydrochalco
- Won, Shen-Jeu,Liu, Cheng-Tsung,Tsao, Lo-Ti,Weng, Jing-Ru,Ko, Horng-Huey,Wang, Jih-Pyang,Lin, Chun-Nan
-
p. 103 - 112
(2007/10/03)
-
- Efficient tetrahydropyranylation of alcohols and detetrahydropyranylation reactions in the presence of catalytic amount of trichloroisocyanuric acid (TCCA) as a safe, cheap industrial chemical
-
Preparation and cleavage of THP ethers of different hydroxy functional groups are easily and efficiently performed in the presence of trichloroisocyanuric acid (TCCA) in the absence of solvent with high yields.
- Firouzabadi, Habib,Iranpoor, Nasser,Hazarkhani, Hassan
-
p. 3623 - 3630
(2007/10/03)
-