Browsing by Subject "IC50"

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    3-Propionyl-thiazolidine-4-carboxylic acid ethyl esters: A family of antiproliferative thiazolidines
    (Royal Society of Chemistry, 2015) Önen-Bayram F.E.; Buran, K.; Durmaz I.; Berk, B.; Cetin-Atalay, R.
    Cancer results from unregulated cell growth. Reactivating the process of the programmed cell death, i.e. apoptosis, is a classical anticancer therapeutic strategy. The apoptosis-inducing property of the (2RS,4R)-2-phenyl-3-propionyl-thiazolidine-4-carboxylic acid ethyl ester (ALC 67) molecule has recently been discovered. We analyzed in this study the impact of the phenyl moiety of this molecule on its biological activity by synthesizing and evaluating analogues where this substituent was replaced by a series of aromatic and aliphatic groups. The results demonstrated that the molecule's antiproliferative property resisted such modifications. Thus, in addition to developing a family of thiazolidine compounds with promising anticancer properties; our investigation revealed that the second position of the thiazolidine ring can be used either to tune the physicochemical properties of ALC67 or to introduce a fluorescent tag to the structure in order to track it in cells and determine its exact molecular mechanism of action. © 2015 The Royal Society of Chemistry.
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    Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles
    (Taylor and Francis Ltd, 2015) Çikla-Süzgün P.; Kaushik-Basu, N.; Basu, A.; Arora P.; Talele, T.T.; Durmaz I.; Çetin-Atalay, R.; Küçükgüzel, S.G.
    Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 M. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound. © 2015 Informa UK Ltd.
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    Phenotype-based variation as a biomarker of sensitivity to molecularly targeted therapy in melanoma
    (Royal Society of Chemistry, 2017) Senses, K. M.; Ghasemi M.; Akbar, M. W.; Isbilen, M.; Fallacara, A. L.; Frankenburg, S.; Schenone, S.; Lotem, M.; Botta, M.; Gure, A. O.
    Transcriptomic phenotypes defined for melanoma have been reported to correlate with sensitivity to various drugs. In this study, we aimed to define a minimal signature that could be used to distinguish melanoma sub-types in vitro, and to determine suitable drugs by which these sub-types can be targeted. By using primary melanoma cell lines, as well as commercially available melanoma cell lines, we find that the evaluation of MLANA and INHBA expression is as capable as one based on a combined analysis performed with genes for stemness, EMT and invasion/proliferation, in identifying melanoma subtypes that differ in their sensitivity to molecularly targeted drugs. Using this approach, we find that 75% of melanoma cell lines can be treated with either the MEK inhibitor AZD6244 or the HSP90 inhibitor 17AAG.
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    Quinoides and VEGFR2 TKIs influence the fate of hepatocellular carcinoma and its cancer stem cells
    (Royal Society of Chemistry, 2017) Kahraman, D. C.; Hanquet, G.; Jeanmart, L.; Lanners, S.; Šramel, P.; Boháč, A.; Cetin-Atalay, R.
    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.