18977-33-8Relevant academic research and scientific papers
Asymmetrical meta-methoxylated diarylpentanoids: Rational design, synthesis and anti-cancer evaluation in-vitro
Leong, Sze Wei,Chia, Suet Lin,Abas, Faridah,Yusoff, Khatijah
, p. 716 - 728 (2018)
In the present study, a series of forty-five asymmetrical meta-methoxylated diarylpentanoids have been synthesized, characterized and evaluated for their in-vitro anti-cancer potential. Among the forty-five analogs, three compounds (20, 33 and 42) have been identified as lead compounds due to their excellent inhibition against five human cancer cell lines including SW620, A549, EJ28, HT1080 and MCF-7. Structure-activity relationship study on cytotoxicity of tested compounds suggested that the presence of meta-oxygenated phenyl ring played a critical role in enhancing their cytotoxic effects. Compounds 33 and 42 in particular, exhibited strongest cytotoxicity against tested cell lines with the IC50 values ranging from 1.1 to 4.3 μM. Subsequent colony formation assay on SW620 cell line showed that both compounds 33 and 42 possessed strong anti-proliferative activity. In addition, flow cytometry based experiments revealed that these compounds could trigger intracellular ROS production thus inducing G2/M-phase cell arrest and apoptosis. All these results suggested that poly meta-oxygenated diarylpentnoid is a promising scaffold which deserved further modification and investigation in the development of natural product-based anti-cancer drug.
Practical Enantioselective Synthesis of Chiroptical Polymers of Intrinsic Microporosity with Circular Polarized Luminescence
Wang, Xinbo,Guo, Hao,Yu, Cong,Jing, Yuanju,Han, Zhaobin,Ma, Xiaohua,Yang, Chenchen,Liu, Minghua,Zhai, Dong,Zheng, Daoyuan,Pan, Yupeng,Li, Xiaoju,Ding, Kuiling
, p. 11180 - 11186 (2021/11/01)
Polymers with intrinsic microporosity (PIMs) have recently received increasing interest in the fields of gas separation, sensors, catalysts, and so on, due to their high microporosity and good solution processability. However, PIMs with chiral backbones a
Mechanistic investigations on substituted benzene sulphonamides as apoptosis inducing anticancer agents
Mettu, Akhila,Naikal James Prameela, Subhashini,Talla, Venu,Thumma, Soujanya
, (2020/01/28)
In an approach to develop potent cytotoxic compounds with targeted action, a systematic methodology was employed to design and initially synthesize parent compounds A1, A8, A13 and A14 followed by synthesis of further analogs of A1 (A2-A7) and A8 (A9-A12)
Ag/P-Stereogenic Phosphine-Catalyzed Enantioselective 1,3-Dipolar Cycloadditions: A Method to Optically Active Pyrrolidines
Zhi, Mengna,Gan, Zhenjie,Ma, Rong,Cui, Hao,Li, Er-Qing,Duan, Zheng,Mathey, Fran?ois
supporting information, (2019/05/07)
A Ag/P-stereogenic phosphine-complex-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with electron-deficient olefins is reported. In this reaction, highly functionalized pyrrolines with a spiro-quaternary stereogenic center were obtained in good yields (up to 99%) with excellent levels of diastereo-(up to >20:1 dr) and enantioselectivities (up to >99% ee). The chirality of adducts was controlled predominantly by the P-stereogenic phosphines.
Symmetrical and unsymmetrical substituted 2,5-diarylidene cyclohexanones as anti-parasitic compounds
Din, Zia Ud,Trapp, Marilia Almeida,Soman de Medeiros, Lívia,Lazarin-Bidóia, Danielle,Garcia, Francielle Pelegrin,Peron, Francieli,Nakamura, Celso Vataru,Rodríguez, Ihosvany Camps,Wadood, Abdul,Rodrigues-Filho, Edson
, p. 596 - 608 (2018/06/20)
Symmetrical and unsymmetrical bis-aryl-α,β-unsaturated ketones were synthesized in moderate to excellent yield by treating cyclohexanone with various aldehydes. Dimethylammonium dimethylcarbamate (DIMCARB) was used as both catalyst and reaction medium for the synthesis of monoarylidenes cycloadduct intermediates, which was further used to produce diarylidene cyclohexanones. All the 34 compounds synthesized were evaluated for their anti-proliferative activity, particularly against promastigote of Leishmania amazonensis, epimastigoteand trypomastigoteof Trypanosoma cruzi. Eighteen compounds displayed anti-leishmanial activity against promastigotes of L. amazonensis with IC50 values ranging from 2.8 to 10 μM. In addition, two compounds exhibited significant antitrypanosomal activity against epimastigotes of T. cruzi with IC50 values of 5.2 ± 0.8 and 3.0 ± 0.0 μM, while five compounds exhibited activity from 15.0 ± 1.4 to 30.2 ± 1.8 μM against trypomastigote of T. cruzi. Moreover, all compounds were more selective against the parasites than the epithelial cells. The unsymmetrical compounds 16, 28, 30 and 33 can be considered as favorable anti-parasitic lead molecule having IC50 and EC50 values in the low-micromolar range, better than the reference drug benznidazole, and low cytotoxicity against Vero cells. The potent compounds were screened in silico against 17 enzymes of T. cruzi and best scoring were found against Dihydroorotate Dehydrogenase.
Chiral Cyclohexyl-Fused Spirobiindanes: Practical Synthesis, Ligand Development, and Asymmetric Catalysis
Zheng, Zhiyao,Cao, Yuxi,Chong, Qinglei,Han, Zhaobin,Ding, Jiaming,Luo, Chenguang,Wang, Zheng,Zhu, Dongsheng,Zhou, Qi-Lin,Ding, Kuiling
supporting information, p. 10374 - 10381 (2018/08/03)
1,1′-Spirobiindane has been one type of privileged skeleton for chiral ligand design, and 1,1′-spirobiindane-based chiral ligands have demonstrated outstanding performance in various asymmetric catalysis. However, the access to enantiopure spirobiindane is quite tedious, which obstructs its practical application. In the present article, a facile enantioselective synthesis of cyclohexyl-fused chiral spirobiindanes has been accomplished, in high yields and excellent stereoselectivities (up to >99% ee), via a sequence of Ir-catalyzed asymmetric hydrogenation of α,α′-bis(arylidene)ketones and TiCl4 promoted asymmetric spiroannulation of the hydrogenated chiral ketones. The protocol can be performed in one pot and is readily scalable, and has been utilized in a 25 g scale asymmetric synthesis of cyclohexyl-fused spirobiindanediol (1S,2S,2′S)-5, in >99% ee and 67% overall yield for four steps without chromatographic purification. Facile derivations of (1S,2S,2′S)-5 provided straightforward access to chiral monodentate phosphoramidites 6a-c and a tridentate phosphorus-amidopyridine 11, which were evaluated as chiral ligands in several benchmark enantioselective reactions (hydrogenation, hydroacylation, and [2 + 2] reaction) catalyzed by transition metal (Rh, Au, or Ir). Preliminary results from comparative studies showcased the excellent catalytic performances of these ligands, with a competency essentially equal to the corresponding well-established privileged ligands bearing a regular spirobiindane backbone. X-ray crystallography revealed a close resemblance between the structures of the precatalysts 20 and 21 and their analogues, which ultimately help to rationalize the almost identical stereochemical outcomes of reactions catalyzed by metal complexes of spirobiindane-derived ligands with or without a fused cyclohexyl ring on the backbone. This work is expected to stimulate further applications of this type of readily accessible skeletons in development of chiral ligands and functional molecules.
Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
Deck, Lorraine M.,Hunsaker, Lucy A.,Vander Jagt, Thomas A.,Whalen, Lisa J.,Royer, Robert E.,Vander Jagt, David L.
, p. 854 - 865 (2017/12/13)
Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues.
Chiral spirodihydroindene skeleton compound and preparation method thereof
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Paragraph 0116-0119; 0121-0122, (2017/02/28)
The invention discloses a chiral spirodihydroindene skeleton compound and a preparation method thereof. The chiral spirodihydroindene skeleton compound is represented by formula I or I'. The preparation method of the chiral spirodihydroindene skeleton compound is characterized in that an intramolecular Friedel-Crafts reaction of a compound represented by formula III is carried out in a solvent under the action of a catalyst to prepare the compound represented by formula I, and the catalyst is a Bronsted acid or a Lewis acid. The preparation method has the advantages of no chiral initial raw material or chiral resolution reagent, no chiral resolution steps, simplicity, simplicity in post-treatment, good economic property, environmental protection, high product yield, and realization of high optical purity and high chemical purity of the product. Transition metal catalyzed asymmetric reaction catalysts prepared by adopting the chiral spirodihydroindene skeleton compound have a substantial catalysis effect, the product yield is greater than 99%, and the ee value of the product higher than 99%.
Synthesis and biological evaluation of new curcumin analogues as antioxidant and antitumor agents: Molecular modeling study
Bayomi, Said M.,El-Kashef, Hassan A.,El-Ashmawy, Mahmoud B.,Nasr, Magda N.A.,El-Sherbeny, Magda A.,Abdel-Aziz, Naglaa I.,El-Sayed, Magda A.-A.,Suddek, Ghada M.,El-Messery, Shahenda M.,Ghaly, Mariam A.
, p. 584 - 594 (2015/07/28)
New curcumin analogues have been synthesized and their antioxidant activities were investigated by measuring their free radical scavenging capacities. The in vitro and in vivo antitumor activities of the synthesized compounds on Ehrlich ascites carcinoma (EAC) cell line were evaluated. 4-(4-Chlorophenyl)-2-(5-ethyl-7-(4-methoxybenzylidene)-3-(4-methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c] pyridin-2-yl)thiazole 7h showed excellent antineoplastic activity in both in vitro and in vivo studies more than that of tested compounds and reference drug, cisplatin. Different molecular modeling studies were performed, where docking of compound 7h into telomerase active site suggested that it could exert its antitumor potential by telomerase inhibition.
Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway
Leow, Pay-Chin,Bahety, Priti,Boon, Choon Pei,Lee, Chong Yew,Tan, Kheng Lin,Yang, Tianming,Ee, Pui-Lai Rachel
, p. 67 - 80 (2014/01/06)
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.
