10421-02-0Relevant articles and documents
Discovery of New Monocarbonyl Ligustrazine-Curcumin Hybrids for Intervention of Drug-Sensitive and Drug-Resistant Lung Cancer
Ai, Yong,Zhu, Bin,Ren, Caiping,Kang, Fenghua,Li, Jinlong,Huang, Zhangjian,Lai, Yisheng,Peng, Sixun,Ding, Ke,Tian, Jide,Zhang, Yihua
, p. 1747 - 1760 (2016)
The elevation of oxidative stress preferentially in cancer cells by inhibiting thioredoxin reductase (TrxR) and/or enhancing reactive oxygen species (ROS) production has emerged as an effective strategy for selectively targeting cancer cells. In this study, we designed and synthesized 21 ligustrazine-curcumin hybrids (10a-u). Biological evaluation indicated that the most active compound 10d significantly inhibited the proliferation of drug-sensitive (A549, SPC-A-1, LTEP-G-2) and drug-resistant (A549/DDP) lung cancer cells but had little effect on nontumor lung epithelial-like cells (HBE). Furthermore, 10d suppressed the TrxR/Trx system and promoted intracellular ROS accumulation and cancer cell apoptosis. Additionally, 10d inhibited the NF-κB, AKT, and ERK signaling, P-gp-mediated efflux of rhodamine 123, P-gp ATPase activity, and P-gp expression in A549/DDP cells. Finally, 10d repressed the growth of implanted human drug-resistant lung cancer in mice. Together, 10d acts a novel TrxR inhibitor and may be a promising candidate for intervention of lung cancer.
Synthesis and cytotoxic activity of phenyl-hexahydropyrrolol[3,4-c]carbazoles
Caballero, Esther,Garcia, Francine,Gravalos, Dolores Ga.,Medarde, Manuel,Sahagun, Heidi,Tome, Fernando
, p. 2459 - 2462 (1996)
A synthetic methodology for the preparation of fused carbazole derivatives has been developed. The presence of a trimethoxyphenyl substituent and the hexahydropyrrolo[3,4-c]carbazole system produced a new family of compounds, that display cytotoxic activi
8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study
Xing, Gang,Zhi, Zhengxing,Yi, Ce,Zou, Jitian,Jing, Xuefeng,Yiu-Ho Woo, Anthony,Lin, Bin,Pan, Li,Zhang, Yuyang,Cheng, Maosheng
, (2021/07/19)
β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β2-agonists with potential applicability in chronic respiratory diseases.
Synthesis and biological evaluations of monocarbonyl curcumin inspired pyrazole analogues as potential anti-colon cancer agent
Hong, Xing,Hu, Xiamin,Min, Zhenli,Ye, Min,Yu, Zhijun,Yuan, Qiong,Zhu, Yue
, p. 2517 - 2534 (2020/07/04)
Purpose: The monocarbonyl analogs of curcumin (MCACs) have been widely studied for their promising antitumor activity. Pyrazole is a five-membered aromatic heterocyclic system with various bioactivities incorporated frequently in drugs. However, few of MCACs inspired pyrazole analogues were investigated. To search for more potent cytotoxic agents based on MCACs, a series of new 1,5-diaryl/heteroaryl-1,4-pentadien-3-ones inspired pyrazole moiety was synthesized and evaluated on their anti-colon cancer activities. Methods: Fifteen new compounds were synthesized and characterized by spectral datum, and then they were tested preliminarily by MTT assay for their cytotoxic activities against a panel of four human cancer cell lines, namely, gastric (SGC-7901), liver (HepG2), lung (A549), and colon (SW620) cancer cells. Compound 7h exhibited excellent selectivity and outstanding anti-proliferation activity against SW620 cells among these 15 compounds. Further, the mechanisms were investigated by transwell migration and invasion assay, clonogenic assay, cell apoptosis analysis, cell cycle analysis, Western blot analysis. Results: The IC50 value of 7h against SW620 cells was 12 nM, being more potent than curcumin (IC50 = 9.36 μM), adriamysin (IC50 = 3.28 μM) and oxaliplatin (IC50 = 13.33 μM). Further assays showed that 7h inhibited SW620 cell migration, invasion and colony formation obviously, which was due to its ability to induce cell cycle arrest in the G2/M and S phases and apoptosis. Western blot assay revealed that 7h decreased the protein expression of ATM gene, which may primarily contribute to its anticancer activity against SW620 cells. Conclusion: A new MCACs 7h was synthesized and found to exhibit excellent anti-proliferation activity against SW620 cells. Further studies indicated that 7h exerted its anticancer activity against SW620 cells probably via decreasing the ATM protein expression. The present study suggested that 7h was a promising candidate as an anti-colon cancer drug for future development.
Highly Stereoselective Synthesis of trans -Dihydronarciclasine Analogues
Varró, Gábor,Mattyasovszky, Lenke,Grün, Alajos,Simon, András,Hegedüs, László,Kádas, István
, p. 625 - 643 (2017/11/27)
Several new trans -dihydronarciclasine analogues were stereo selectively synthesised by applying our feasible and efficient process developed recently. These new phenanthridone alkaloid derivatives were obtained in both racemic and optically active forms. During their enantioselective syntheses, high selectivities (up to 99% ee) were achieved by using (8 S,9 S)-9-amino(9-deoxy)epiquinine as an organocatalyst. The modifications, the introduction of ethoxy or methoxy groups, were made in ring A of the phenanthridone scaffold.
Discovery of curcumin inspired sulfonamide derivatives as a new class of carbonic anhydrase isoforms I, II, IX, and XII inhibitors
Ramya, P. V. Sri,Angapelly, Srinivas,Angeli, Andrea,Digwal, Chander Singh,Arifuddin, Mohammed,Babu, Bathini Nagendra,Supuran, Claudiu T.,Kamal, Ahmed
, p. 1274 - 1281 (2017/10/09)
A series of curcumin inspired sulfonamide derivatives was prepared from various chalcones and 4-sulfamoyl benzaldehyde via Claisen–Schmidt condensation. All new compounds were assayed as inhibitors of four human isoforms of the metalloenzyme carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I, II, IX and XII. Interesting inhibitory activities were observed against all these isoforms. hCA I, an isoform involved in several eye diseases was inhibited moderately with KIs in the range of 191.8–904.2 nM, hCA II, an antiglaucoma drug target was highly inhibited by the new sulfonamides, with KIs in the range of 0.75–8.8 nM. hCA IX, a tumor-associated isoform involved in cancer progression and metastatic spread was potently inhibited by the new sulfonamides, with KIs in the range of 2.3–87.3 nM, whereas hCA XII, and antiglaucoma and anticancer drug target, was inhibited with KIs in the range of 6.1–71.8 nM. It is noteworthy that one of the new compounds, 5d, was found to be almost 9 times more selective against hCA II (KI = 0.89 nM) over hCA IX and hCA XII, whereas 5e was 3 and 70 times more selective against hCA II (KI = 0.75 nM) over hCA IX and hCA XII, respectively.
Novel diarylheptanoids as inhibitors of TNF-α production
Dhuru, Sameer,Bhedi, Dilip,Gophane, Dnyaneshwar,Hirbhagat, Kiran,Nadar, Vijaya,More, Dattatray,Parikh, Sapna,Dalal, Roda,Fonseca, Lyle C.,Kharas, Firuza,Vadnal, Prashant Y.,Vishwakarma, Ram A.,Sivaramakrishnan
supporting information; experimental part, p. 3784 - 3787 (2011/07/31)
Synthesis and anti-inflammatory activity of novel diarylheptanoids [5-hydroxy-1-phenyl-7-(pyridin-3-yl)-heptan-3-ones and 1-phenyl-7-(pyridin-3-yl) hept-4-en-3-ones] as inhibitors of tumor necrosis factor-α (TNF-α) production is described in the present article. The key reactions involve the formation of a β-hydroxyketone by the reaction of substituted 4-phenyl butan-2-ones with pyridine-3-carboxaldehyde in presence of LDA and the subsequent dehydration of the same to obtain the α,β-unsaturated ketones. Compounds 4i, 5b, 5d, and 5g significantly inhibit lipopolysaccharide (LPS)-induced TNF-α production from human peripheral blood mononuclear cells in a dose-dependent manner. Of note, the in vitro TNF-α inhibition potential of 5b and 5d is comparable to that of curcumin (a naturally occurring diarylheptanoid). Most importantly, oral administration of 4i, 5b, 5d, and 5g (each at 100 mg/kg) but not curcumin (at 100 mg/kg) significantly inhibits LPS-induced TNF-α production in BALB/c mice. Collectively, our findings indicate that these compounds may have potential therapeutic implications for TNF-α-mediated auto-immune/inflammatory disorders.
Synthesis and Antimalarial Properties of 1-Imino Derivatives of 7-Chloro-3-substituted-3,4-dihydro-1,9(2H,10H)-acridinediones and Related Structures
Kesten, Stephen J.,Degnan, Margaret J.,Hung, Jocelyn,McNamara, Dennis J.,Ortwine, Daniel F.,et al.
, p. 3429 - 3447 (2007/10/02)
To improve upon the activity and properties of the 3-aryl-7-chloro-3,4-dihydro-1,9(2H,10H)-acridinediones, a variety of 1-imino derivatives (3) were prepared and shown to be highly active antimalarial agents in both rodents and primates.Among structural modifications prepared, including N10-alkyl and C2-substituted analogs, removal of the C9 oxygen, and introduction of an imino side chain at C9, the imines of the N10-H acridinediones were the most active compounds obtained.The imino derivative of7-chloro-3-(2,4-dichlorophenyl)-3,4-dihydro-1,9(2H,10H)-acridinedione (9aa) proved to be highly active in advanced studies in primates.
