- Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and 'click' strategy
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Abstract To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluations against HepG2, Caski and HeLa cell lines, three steroidal triazoles 5b, 5f and 5m in this library were found to possess potent anti-proliferative effects against Caski cells with the half-inhibitory concentrations (IC50) of 9.4-11.8 μM. The high-efficient and straightforward process was attractive feature for facile preparation of anti-tumor steroidal triazoles.
- Lu, Xiao-Feng,Yang, Zheng,Huang, Nian-Yu,He, Hai-Bo,Deng, Wei-Qiao,Zou, Kun
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- Indole-linked 1,2,3-triazole derivatives efficiently modulate COX-2 protein and PGE2 levels in human THP-1 monocytes by suppressing AGE-ROS-NF-kβ nexus
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Aims: AGEs augment inflammatory responses by activating inflammatory cascade in monocytes, and hence lead to vascular dysfunction. The current study aims to study a plausible role and mechanism of a new library of indole-tethered 1,2,3-triazoles 2-13 in A
- Aslam, Tooba,Basha, Fatima Z.,Choudhary, M. Iqbal,Iqbal, Shazia,Jahan, Humera,Khan, Maria Aqeel,Siddiqui, Nimra Naz
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- Copper-Catalyzed Oxidative Difunctionalization of Terminal Unactivated Alkenes
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The copper(II)-promoted free-radical oxidative difunctionalization of terminal alkenes to access ketoazides by utilizing molecular oxygen has been reported. A series of styrene derivatives have been evaluated and were found to be compatible to give the desired difunctionalized products in moderate to good yields. The role of molecular oxygen both as an oxidant and oxygen atom source in this catalytic transformation has been unquestionably demonstrated by 18O-labeling studies and a radical mechanistic pathway involving the oxidative formation of azidyl radicals is also designed. This environment-friendly catalytic oxidative protocol can transform aldehyde to nitrile.
- Hussain, Muhammad Ijaz,Feng, Yangyang,Hu, Liangzhen,Deng, Qingfu,Zhang, Xiaohui,Xiong, Yan
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supporting information
p. 7852 - 7859
(2018/05/30)
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- Quinoides and VEGFR2 TKIs influence the fate of hepatocellular carcinoma and its cancer stem cells
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Bioactivities of quinoides 1-5 and VEGFR2 TKIs 6-10 in hepatocellular cancer (HCC) and cancer stem cells (HCSCs) were studied. The compounds exhibited IC50 values in μM concentrations in HCC cells. Quinoide 3 was able to eradicate cancer stem cells, similar to the action of the stem cell inhibitor DAPT. However, the more cytotoxic VEFGR TKIs (IC50: 0.4-3.0 μM) including sorafenib, which is the only FDA approved drug for the treatment of HCC, enriched the hepatocellular cancer stem cell population by 2-3 fold after treatment. An aggressiveness factor (AF) was proposed to quantify the characteristics of drug candidates for their ability to eradicate the CSC subpopulation. Considering the tumour heterogeneity and marker positive cancer stem cell like subpopulation enrichment upon treatments in patients, this study emphasises the importance of the chemotherapeutic agent choice acting differentially on all the subpopulations including marker-positive CSCs.
- Kahraman, Deniz Cansen,Hanquet, Gilles,Jeanmart, Lo?c,Lanners, Steve,?ramel, Peter,Bohá?, Andrej,Cetin-Atalay, Rengul
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supporting information
p. 81 - 87
(2017/02/05)
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- In vitro α-glucosidase inhibition by non-sugar based triazoles of dibenzoazepine, their structure-Activity relationship, and molecular docking
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Background: α-Glucosidase inhibitors (AGIs) have been reported for their clinical potential against postprandial hyperglycemia, which is responsible for the risks associated with diabetes mellitus 2 and cardiovascular diseases (CVDs). Besides, a number of
- Khan, Maria A.,Javaid, Kulsoom,Batool, Farhana,Basha, Fatima Z.,Choudhary, Muhammad I.,Wadood, Abdul,Jamal, Alam,Fazal-Ur-Rehman, Saba
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p. 698 - 704
(2018/02/02)
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- Synthesis and in vitro evaluation of dibenzoazepine triazole derivatives: A novel class of antileishmanial agents
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In the present study, a series of dibenzoazepine triazole derivatives (24-39) were synthesized and evaluated for their in vitro bioactivities including antiglycation, antibacterial, DPPH radical scavenging, urease inhibition, antileishmanial and immunomod
- Khan, Maria Aqeel,Saleem, Aliyan,Ghouri, Nida,Hameed, Abdul,Iqbal Choudhary,Basha, Fatima Z.
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p. 597 - 606
(2016/03/22)
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- Asymmetric aldol addition of α-azido ketones to ethyl pyruvate mediated by a cinchona-based bifunctional urea catalyst Dedicated to the memory of Prof. Dr. Ayhan S. Demir
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The first asymmetric synthesis of ethyl 4-aryl-3-azido-2-hydroxy-2-methyl- 4-oxobutanoates via a cinchona organocatalyst induced aldol addition of α-azido ketones to ethyl pyruvate has been developed. The coupling reaction under optimized conditions was carried out to furnish tetrafunctionalized synthons with enantioselectivities of up to 91:9 and enriched diastereoselectivities of up to 95:5 (syn:anti).
- Okumu?, Seda,Tanyeli, Cihangir,Demir, Ayhan S.
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supporting information
p. 4302 - 4305
(2014/07/22)
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- HEPATITIS C VIRUS INHIBITORS
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This disclosure concerns novel compounds of Formula (I) or as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
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Page/Page column 74
(2011/06/16)
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- Synthesis, monoamine transporter binding, properties, and functional monoamine uptake activity of 3β-[4-methylphenyl and 4-chlorophenyl]- 2β-[5-(substituted phenyl)thiazol-2-yl]tropanes
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Synthetic methods were developed for the synthesis of the 3β-(4-substituted phenyl)-2β-[5-(substituted phenyl)thiazol-2-yl] tropanes (4a-s). The compounds were evaluated for their monoamine transporter binding and monoamine uptake inhibition properties using both rat brain tissue and cloned transporter assays. In general, the compounds showed higher dopamine transporter (DAT) affinity relative to the serotonin and norepinephrine transporters (SERT and NET, respectively) and greater [3H]dopamine uptake inhibition potency relative to [3H]serotonin and [ 3H]norepinephrine uptake inhibition. Several compounds were DAT selective relative to the SERT and NET in the monoamine transporter binding assays. The most potent and selective analog in the functional monoamine uptake inhibition test was 3β-(4-methylphenyl-2β-[5-(3-nitrophenyl)thiazol-2- yl]tropane (4p).
- Gong, Paul K.,Blough, Bruce E.,Brieaddy, Lawrence E.,Huang, Xiaodong,Kuhar, Michael J.,Navarro, Hernán A.,Carroll, F. Ivy
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p. 3686 - 3695
(2008/02/10)
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- Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors
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A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as inhibitors of VEGFR2 kinase. Herein we describe the structure-activity relationship (SAR) of this novel template. Optimization of both aryl rings led to very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts. X-ray crystallography confirmed the proposed binding mode, and comparison of oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl ring.
- Harris, Philip A.,Cheung, Mui,Hunter III, Robert N.,Brown, Matthew L.,Veal, James M.,Nolte, Robert T.,Wang, Liping,Liu, Wendy,Crosby, Renae M.,Johnson, Jennifer H.,Epperly, Andrea H.,Kumar, Rakesh,Luttrell, Deirdre K.,Stafford, Jeffrey A.
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p. 1610 - 1619
(2007/10/03)
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