- Synthesis of new symmetric cyclic and acyclic halocurcumin analogues typical precursors for hybridization
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Abstract: It is believed that the synthesis of hybrid molecules containing different biologically relevant moieties would furnish multifunctional drugs with the possible synergism of potential importance for the treatment of cancer, diabetic and Alzheimer
- Noureddin, Sawsan A.,El-Shishtawy, Reda M.,Al-Footy, Khalid O.
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- Photoresponsive real time monitoring silicon quantum dots for regulated delivery of anticancer drugs
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Recently, photoresponsive nanoparticles have been widely used to develop drug delivery systems (DDSs) wherein light is used as an external stimulus to trigger drug release in a spatially and temporally controlled fashion. Real time monitoring DDSs are also gaining much interest due to their capability of monitoring drug release in situ. In this context we designed a new photoresponsive real time monitoring nanoparticle based on photoluminescent silicon quantum dots (SiQDs) using the o-nitrobenzyl (ONB) derivative as a phototrigger for the controlled release of anticancer drug chlorambucil (Cbl). The strong fluorescence of SiQDs was initially quenched by ONB. Upon irradiation ONB triggered the release of the drug switching on the fluorescence of SiQDs to monitor the drug release. We reported a new and simple strategy to synthesise amine functionalised silicon quantum dots and covalently conjugated phototrigger ONB with caged anticancer drug Cbl onto it. Newly designed photoresponsive theranostic ONBCbl-SiQDs performed three important functions: (i) nanocarriers for drug delivery, (ii) controlled drug release under both one photon and two-photon excitation, and (iii) photoswitchable fluorescent nanoparticles for real-time monitoring of drug release based on the photoinduced electron transfer (PET) process. In vitro biological studies revealed the efficient cellular internalisation and cancer cell destruction ability of ONBCbl-SiQDs upon photoirradiation. ONBCbl-SiQDs exhibit a successful example of combining multiple functions into a single system for drug delivery systems.
- Paul, Amrita,Jana, Avijit,Karthik,Bera, Manoranjan,Zhao, Yanli,Singh, N.D. Pradeep
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- 1st generation dendrimeric antioxidants containing Meldrum's acid moieties as surface groups
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Free radical-caused oxidative stress can be reduced by various antioxidants. A new and promising type of antioxidant are monosubstituted Meldrum's acids. Herein the first dendritic architecture with 1,3-dioxane-4,6-dione units as surface groups is presented. The compounds were synthesized through the alkylation of phenol, the Knoevenagel condensation and sequential reduction. The antiradical activity (AA) against 1,1-diphenyl-2-picryl hydrazyl (DPPH) for all compounds is 80-90%, and the IC50 varies from 10-35 μM. These data are comparable with vitamin C, t-butylhydroquinone (TBHQ) or vitamin E. The AA against galvinoxyl (GO) increased with the number of surface groups. The AA was comparable with butylated hydroxytoluene (BHT) for compounds with at least two moieties of 1,3-dioxane-4,6-dione. The structure with a flexible glycerol core is highlighted among all the derivatives. Although the AA against DPPH for the glycerol derivative is comparable with those with aromatic cores it is more effective against GO (AA = 95%, IC50 = 60 μM): the AA is greater than for vitamin C and BHT. Thus, a flexible structure seems to be a promising core for elaborating powerful antioxidants with Meldrum's acid surface groups. This journal is
- Ai?pure, Klaudija,Jure, Māra,Mieri?a, Inese,Peipi?a, Elīna
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p. 607 - 620
(2022/01/22)
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- Synthesis of novel monocarbonyl curcuminoids, evaluation of their efficacy against MRSA, including ex vivo infection model and their mechanistic studies
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In continuation of our effort to improve the physiological stability and the antibacterial activity of curcuminoids against drug-resistant bacteria, a series of novel monocarbonyl curcuminoids were synthesized and screened for antibacterial activity against S. aureus and E. coli strains. These curcuminoids showed potent antibacterial activity against both methicillin-sensitive and methicillin-resistant strains of S. aureus with MIC values 2–8 and 4–16 μg/mL, respectively. They also exhibited moderate potency against E. coli strains. The four most active curcuminoids (7d, 7i, 7m, and 7p) were on further investigation found to be very stable under physiological conditions, non-hemolytic, and non-toxic toward mammalian cells up to 150 μg/mL concentration. Mechanistic studies revealed that these curcuminoids displayed potent bactericidal activity by targeting cell membranes. Further, in an ex vivo mammalian co-culture infection model study, remarkably, the curcuminoids 7i and 7p were able to clear the internalized bacteria in mammalian cells and the activity was found to be superior to conventional antibiotics such as vancomycin and linezolid. Therefore, the present study affords us water-soluble, stable, non-toxic curcuminoids that may serve as lead molecules for development as antibacterial agents against MRSA infections.
- Gagandeep,Kandi, Shamseer Kulangara,Kumar, Prince,Mukhopadhyay, Kasturi,Rawat, Diwan S.
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- Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation
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Inflammation is a complex biological response to stimuli. Activated macrophages induced excessively release of pro-inflammatory cytokines and mediators such as endogenous radical nitric oxide (NO) play a significant role in the progression of multiple inflammatory diseases. Both natural and synthetic chalcones possess a wide range of bioactivities. In this work, thirty-nine chalcones and three related compounds, including several novel ones, based on bioactive kava chalcones were designed, synthesized and their inhibitory effects on NO production in RAW 264.7 cells were evaluated. The novel compound (E)-1-(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (53) exhibited a better inhibitory activity (84.0%) on NO production at 10 μM (IC50 = 6.4 μM) with the lowest cytotoxicity (IC50 > 80 μM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress the progression of inflammation on collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models. In addition, the structure-activity relationship (SAR) of the kava chalcones based analogs was also depicted.
- Chen, Lijuan,Fan, Tiantian,Lei, Xiangui,Teichmann, Alexander Tobias,Wang, Amu,Wang, Chao,Wei, Zhe,Wieland, Frank Heinrich,Yang, Youzhe,Yin, Jinxiang,Zhou, Li,Zhu, Yue
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- Photoredox Catalyst Free, Visible Light-Promoted C3?H Acylation of Quinoxalin-2(1H)-ones in Water
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A method for the synthesis of 3-acyl quinoxalin-2(1H)-ones through visible-light promoted decarboxylative acylation of α-oxo-carboxylic acids with quinoxalin-2(1H)-ones was developed. The reaction was performed in aqueous phase and photoredox catalyst was not required to run the process. (Figure presented.).
- Lu, Juan,He, Xiang-Kui,Cheng, Xiao,Zhang, Ai-Jun,Xu, Guo-Yong,Xuan, Jun
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supporting information
p. 2178 - 2182
(2020/03/19)
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- Design, synthesis, bioactivity and mechanism of dithioacetal derivatives containing dioxyether moiety
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The present work designed and synthesized a series of dithioacetal derivatives containing dioxyether, as well as evaluated their antiviral activities against tobacco mosaic virus (TMV). Bioassays demonstrated that the target compounds showed excellent ant
- Wang,Zhang, Jian,He, Fangcheng,Gan, Xiuhai,Song,Hu, Deyu
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p. 2218 - 2223
(2019/07/03)
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- A Strategy for Specific Fluorescence Imaging of Monoamine Oxidase A in Living Cells
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Monoamine oxidase (MAO) has two isoforms, MAO-A and MAO-B, which show different functions, and thus selective fluorescence imaging is important for biological studies. Currently, however, specific detection of MAO-A remains a great challenge. Herein, we r
- Wu, Xiaofeng,Shi, Wen,Li, Xiaohua,Ma, Huimin
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supporting information
p. 15319 - 15323
(2017/11/30)
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- Synthesis of different heterocycles-linked chalcone conjugates as cytotoxic agents and tubulin polymerization inhibitors
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A series of new heterocycles-linked chalcone conjugates has been designed and synthesized by varying different alkane spacers. These conjugates were tested for their in vitro cytotoxic potential against a panel of selected human cancer cell lines namely,
- Shankaraiah, Nagula,Nekkanti, Shalini,Brahma, Uma Rani,Praveen Kumar, Niggula,Deshpande, Namrata,Prasanna, Daasi,Senwar, Kishna Ram,Jaya Lakshmi, Uppu
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p. 4805 - 4816
(2017/10/05)
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- Design and synthesis of 4′-O-alkylamino-tethered-benzylideneindolin-2-ones as potent cytotoxic and apoptosis inducing agents
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A series of new 4′-O-alkylamino-tethered-benzylideneindolin-2-one derivatives has been synthesized and evaluated for their anti-proliferative activity against selected human cancer cell lines of lung (A549), prostate (DU-145), breast (BT549 and MDA-MB-231) and normal breast epithelial cells (MCF-10A). Gratifyingly, the compounds 5j, 5o and 5r exhibited potent cytotoxicity against breast cancer cell lines (BT549 and MDA-MB-231) with IC50values in the range of 1.26–2.77?μM, and are found to be safer with lesser cytotoxicity on normal breast epithelial cells (MCF-10A). Further, experiments were conducted with these compounds 5j, 5o and 5r on MDA-MB-231 cancer cells to study the mechanism of growth inhibition and apoptosis inducing effect. Treatment of MDA-MB-231 cells with test compounds resulted in inhibition of cell migration through disorganization and disruption of F-actin capping protein. The flow-cytometry analysis results showed that the compound 5o arrested MDA-MB-231 cells in G0/G1 phase of cell cycle in a dose dependent manner. Hoechst staining study revealed that the test compounds inhibited tumor cell proliferation through induction of apoptosis. In addition, the mitochondrial membrane potential (DΨm) was affected and the increased level of reactive oxygen species (ROS) was noted in MDA-MB-231 cells.
- Senwar, Kishna Ram,Reddy, T. Srinivasa,Thummuri, Dinesh,Sharma, Pankaj,Bharghava, Suresh K.,Naidu,Shankaraiah, Nagula
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p. 4061 - 4069
(2016/08/01)
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- Design, synthesis, and anticancer evaluation of long-chain alkoxylated mono-carbonyl analogues of curcumin
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Curcumin is a nontoxic phenolic compound that modulates the activity of several cellular targets that have been linked with cancers and other chronic diseases. However, the efficacy of curcumin in the clinic has been limited by its poor bioavailability an
- Weng, Qiaoyou,Fu, Lili,Chen, Gaozhi,Hui, Junguo,Song, Jingjing,Feng, Jianpeng,Shi, Dengjian,Cai, Yuepiao,Ji, Jiansong,Liang, Guang
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- Synthesis of unsymmetrical c5-curcuminoids as potential anticancer agents
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Cancer and malaria are two major diseases, which have devastating effects on public health systems. In a quest of developing new anticancer and antimalarial agents, a series of 22 unsymmetrical C5-curcumionds was synthesized and evaluated for their anticancer activity against HeLa, KB, PC3 and DU145 cancer cell lines. Out of these, four compounds displayed potent activity in HeLa cancer cell line (IC50 ranging from 0.7 to 0.9 μM) than standard FDA-approved drug doxorubicin (IC50 = 1.7 μM). They also showed weak to moderate activity against other cancer cell lines. Unsymmetrical C5-curcumionids were also evaluated for their antimalarial activity against CQ-sensitive and CQ-resistant strains of P. falciparum. Weak antimalarial activities were observed with some compounds without any toxicity towards the mammalian cell line at the highest tested concentration of 10 μM.
- Manohar, Sunny,Thakur, Anuj,Khan, Shabana I.,Sun, Guojing,Ni, Nanting,Wang, Binghe,Rawat, Diwan S.
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p. 138 - 149
(2014/03/21)
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- Synthesis, antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin
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A series of novel monocarbonyl analogues of curcumin have been designed, synthesized and tested for their activity against Molt4, HeLa, PC3, DU145 and KB cancer cell lines. Six of the analogues showed potent cytotoxicity towards these cell lines with IC50 values below 1 μM, which is better than doxorubicin, a US FDA approved drug. Several analogues were also found to be active against both CQ-resistant (W2 clone) and CQ-sensitive (D6) strains of Plasmodium falciparum in an in-vitro antimalarial screening. This level of activity warrants further investigation of the compounds for development as anticancer and antimalarial agents.
- Manohar, Sunny,Khan, Shabana I.,Kandi, Shamseer Kulangara,Raj, Kranthi,Sun, Guojing,Yang, Xiaochuan,Calderon Molina, Angie D.,Ni, Nanting,Wang, Binghe,Rawat, Diwan S.
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supporting information
p. 112 - 116
(2013/02/23)
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- Syntheses and evaluation of novel isoliquiritigenin derivatives as potential dual inhibitors for amyloid-beta aggregation and 5-lipoxygenase
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A series of new isoliquiritigenin (ISL) derivatives were synthesized and evaluated as dual inhibitors for amyloid-beta (Aβ) aggregation and 5-lipoxygenase (5-LO). It was found that all these synthetic compounds inhibited Aβ (1-42) aggregation effectively with their IC50 values ranged from 2.2 ± 1.5 μM to 23.8 ± 2.0 μM. These derivatives also showed inhibitory activity to 5-LO with their IC50 values ranged from 6.1 ± 0.1 μM to 35.9 ± 0.3 mM. Their structure-activity relationships (SAR) and mechanisms of inhibitions were studied. This study provided potentially important information for further development of ISL derivatives as multifunctional agents for Alzheimer's disease (AD) treatment.
- Chen, Yi-Ping,Zhang, Zi-Ying,Li, Yan-Ping,Li, Ding,Huang, Shi-Liang,Gu, Lian-Quan,Xu, Jun,Huang, Zhi-Shu
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- Control of conformational flexibility in calix[6]arenes: Synthesis and characterisation of triply bridged calix[6]arene - 10, 15-dihydro-5H-tribenzo [a,d,g]cyclononene conjugates
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A series of triply bridged symmetrical terf-butylcalix[6]arene-10,15- dihydro-5H-tribenzo[a,d,g]cyclononene conjugates have been synthesised in excellent yields. It has been observed that the synthesised multi-cavity molecular receptors retain the calix[6
- Chawla, H. Mohindra,Shrivastava, Rahul
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experimental part
p. 347 - 353
(2009/06/18)
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- Design and synthesis of 6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid derivatives as PPARγ activators
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The design and synthesis of novel series of 6-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid (pyrimidone) derivatives that are high affinity ligands for peroxisome proliferators activated receptor γ have been reported as a potential substitu
- Kumar, Rakesh,Mittal, Amit,Ramachandran, Uma
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p. 4613 - 4618
(2008/03/11)
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- Curcumin and dehydrozingerone derivatives: Synthesis, radiolabeling, and evaluation for β-amyloid plaque imaging
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Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been s
- Ryu, Eun Kyoung,Choe, Yearn Seong,Lee, Kyung-Han,Choi, Yong,Kim, Byung-Tae
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p. 6111 - 6119
(2007/10/03)
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- Radical isomerization via intramolecular ipso substitution of aryl ethers: Aryl translocation from oxygen to carbon
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Bromopropyl aryl ethers an converted to 3-arylpropanols under standard radical generating conditions in the presence of tributylstannane and AIBN. This rearrangement involves intramolecular ipso attack of the alkyl radicals which generates spiro cyclohexadienyl radical intermediates.
- Lee, Eun,Lee, Chulbom,Tae, Jin Sung,Whang, Ho Sung,Li, Kap Sok
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p. 2343 - 2346
(2007/10/02)
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