Browsing by Subject "antineoplastic agent"

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Open Access
Benzothiazole derivatives as human DNA topoisomerase IIα inhibitors
(2013) Kaplan-Ozen, C.; Tekiner-Gulbas, B.; Foto, E.; Yildiz I.; Diril, N.; Aki, E.; Yalcin I.
Benzothiazole derivatives resembling the structure of DNA purine bases were tested to determine their topoisomerase inhibition activities. Based on DNA topoisomerase I and II relaxation assay results, all 12 derivatives acted as human topoisomerase IIα inhibitors, whereas only two compounds inhibited Calf thymus topoisomerase I. 3-amino-2-(2-bromobenzyl)-1,3-benzothiazol-3-ium 4-methylbenzensulfonate (BM3) was observed to be the most effective human topoisomerase IIα inhibitor with the lowest IC50 value of 39 nM. The mechanistic studies suggested that BM3 was neither a DNA intercalator nor a topoisomerase poison, it was only a DNA minor groove-binding agent. BM3 initially bound to the DNA topoisomerase IIα enzyme, then to DNA. As a result, the tested benzothiazole derivatives were obtained as strong topoisomerase IIα inhibitors. The benzothiazole tosylated salt form BM3 was found as the most effective topoisomerase IIα inhibitor. BM3's mechanisms of action might be its direct interaction with the enzyme. BM3's minor groove-binding property might also contribute to this action. Hence, BM3 could be a good candidate as a new anticancer agent. © 2013 Springer Science+Business Media New York.
Open Access
Cost-effectiveness of adjuvant FOLFOX and 5FU/LV chemotherapy for patients with stage II colon cancer
(2013) Ayvaci, M.U.S.; Shi J.; Alagoz O.; Lubner, S.J.
Purpose. We evaluated the cost-effectiveness of adjuvant chemotherapy using 5-fluorouracil, leucovorin (5FU/LV), and oxaliplatin (FOLFOX) compared with 5FU/LV alone and 5FU/LV compared with observation alone for patients who had resected stage II colon cancer. Methods. We developed 2 Markov models to represent the adjuvant chemotherapy and follow-up periods and a single Markov model to represent the observation group. We used calibration to estimate the transition probabilities among different toxicity levels. The base case considered 60-year-old patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer and were medically fit to receive 6 months of adjuvant chemotherapy. We measured health outcomes in quality-adjusted life-years (QALYs) and estimated costs using 2007 US dollars. Results. In the base case, adjuvant chemotherapy of the FOLFOX regimen had an incremental cost-effectiveness ratio (ICER) of $54,359/QALY compared with the 5FU/LV regimen, and the 5FU/LV regimen had an ICER of $14,584/QALY compared with the observation group from the third-party payer perspective. The ICER values were most sensitive to 5-year relapse probability, cost of adjuvant chemotherapy, and the discount rate for the FOLFOX arm, whereas the ICER value of 5FU/LV was most sensitive to the 5-year relapse probability, 5-year survival probability, and the relapse cost. The probabilistic sensitivity analysis indicates that the ICER of 5FU/LV is less than $50,000/QALY with a probability of 99.62%, and the ICER of FOLFOX as compared with 5FU/LV is less than $50,000/QALY and $100,000/QALY with a probability of 44.48% and 97.24%, respectively. Conclusion. Although adjuvant chemotherapy with 5FU/LV is cost-effective at all ages for patients who have undergone an uncomplicated hemicolectomy for stage II colon cancer, FOLFOX is not likely to be cost-effective as compared with 5FU/LV.
Open Access
Cytotoxic activities of some benzothiazole-piperazine derivatives
(Taylor and Francis Ltd, 2015) Gurdal, E.E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.
Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Compound 1d is highly cytotoxic against all tested cancer cell lines. Further investigation of compound 1d by Hoechst Staining and Fluorescence-Activated Cell Sorting Analysis (FACS) revealed that this compound causes apoptosis by cell cycle arrest at subG1 phase. © 2014 Informa UK Ltd. All rights reserved.
Open Access
Cytotoxic activities of some novel benzhydrylpiperazine derivatives
(Georg Thieme Verlag, 2013) Gurdal, E. E.; Yarim, M.; Durmaz, I.; Cetin Atalay, R.
This study presents the synthesis of nineteen 1-(substitutedbenzoyl)-4- benzhydrylpiperazine and 1-[(substitutedphenyl)sulfonyl]-4-benzhydrylpiperazine derivatives. In vitro cytotoxic activities of the compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Among the test compounds, benzamide derivatives had high cytotoxic activity whereas sulfonamide derivatives showed variable 50% growth inhibition (GI50). © Georg Thieme Verlag KG Stuttgart · New York.
Open Access
Gadolinium leakage into subarachnoid space and cystic metastases
(2013) Elçin Yildiz, A.; Atli, E.; Karli Oǧuz, K.
Subarachnoid space (SAS) and cystic metastatic lesions of brain parenchyma appear hypointense on fluid-attenuated inversion-recovery (FLAIR) and T1-weighted magnetic resonance imaging (MRI) unless there is a hemorrhage or elevated protein content. Otherwise, delayed enhancement and accumulation of contrast media in SAS or cyst of metastases should be considered. We present hyperintense SAS and cystic brain metastases of lung cancer on FLAIR and T1-weighted MRI, respectively, in a patient who had been previously given contrast media for imaging of spinal metastases and had mildly impaired renal functions, and discuss the relevant literature. © Turkish Society of Radiology 2013.
Open Access
Synthesis and anticancer activity evaluation of some benzothiazole-piperazine derivatives
(Bentham Science Publishers B.V., 2015) Gurdal, E.E.; Buclulgan, E.; Durmaz I.; Cetin-Atalay, R.; Yarim, M.
Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Aroyl substituted compounds 1h and 1j were found to be the most active derivatives. In addition, further investigation of compounds 1h and 1j by Hoechst staining and FACS revealed that these compounds cause apoptosis by cell cycle arrest at subG1 phase. © 2015 Bentham Science Publishers.
Open Access
Synthesis of 3-aroyl-4-aryl-1-isopropylamino-4-piperidinols and evaluation of the cytotoxicities of the compounds against human hepatoma and breast cancer cell lines
(Taylor and Francis Ltd, 2015) Kucukoglu, K.; Mete, E.; Cetin-Atalay, R.; Gul H.I.
Some 4-piperidinol derivatives were synthesized and their cytotoxicity was tested against human hepatoma (Huh7) and breast cancer (T47D) cells. Aryl part was changed as phenyl in 2a, 4-methylphenyl in 2b, 4-methoxyphenyl in 2c, 4-chlorophenyl in 2d, 4-fluorophenyl in 2e, 4-bromophenyl in 2f, 4-nitrophenyl in 2g and 2-thienyl in 3. Compounds were synthesized and reported for the first time by this study except 2a and 2d. Chemical structures were confirmed by 1H NMR, 13C NMR, IR, MS and elemental analyses. Compounds 2a (3.1 times), 2c (3.8 times), 2f (4.6 times), 2g (1.3 times) and 3 (3.2 times) had 1.3-4.6 times higher cytotoxic potency than the reference compound 5-FU against Huh7 cell line while all the compounds synthesized had shown lower activities against T47D cell line than 5-FU. In the light of these results, compounds 2a, 2c, 2f, 2g and 3 may serve as model compounds for further studies. © 2014 Informa UK Ltd.
Open Access
Synthesis of novel substituted purine derivatives and identification of the cell death mechanism
(Elsevier Masson SAS, 2015) Demir, Z.; Guven, E.B.; Ozbey, S.; Kazak, C.; Atalay, R.C.; Tuncbilek, M.
Novel substituted adenine and purine derivatives were designed and synthesized.Compound 36 displayed the greatest cytotoxic activity with IC50 less than 1 1/4M.36 induces senescence associated cell death, which was demonstrated with SA2-Gal assay. © 2014 Elsevier Masson SAS.