Browsing by Subject "Cytotoxicity"
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Item Open Access Biocompatible supramolecular catalytic one-dimensional nanofibers for efficient labeling of live cells(American Chemical Society, 2015) Khalily, M. A.; Gulseren, G.; Tekinay, A. B.; Güler, Mustafa O.Understanding complex cellular functions requires study and tracking of biomolecules such as proteins, glycans, and lipids in their natural environment. Herein, we report the first supramolecular nanocatalyst for bioorthogonal click reaction to label live cells. This biocompatible and biodegradable nanocatalyst was formed by self-assembled peptide nanofibers complexed with copper ions. The supramolecular nanocatalyst enhanced azide-alkyne cycloaddition reaction rate under physiological conditions and was shown to be useful for efficient bioorthogonal labeling of live cells.Item Open Access Cancer cell Cytotoxicities of 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl) piperazine derivatives(M D P I AG, 2012) Yarim, M.; Koksal, M.; Durmaz, I.; Atalay, R.A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a-g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and 1H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B), breast (MCF7, BT20, T47D, CAMA-1), colon (HCT-116), gastric (KATO-3) and endometrial (MFE-296) cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compound. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines. © 2012 by the authors; licensee MDPI, Basel, Switzerland.Item Open Access Class IA PI3K isoforms lead to differential signalling downstream of PKB/Akt(Walter De Gruyter GMBH, 2023-12-20) Çatalak Yılmaz, Hazal Beril; Sulaiman, Mahnoor; Işık, Özlem Aybüke; Çizmecioğlu, OnurObjectives The catalytic subunits of Class IA PI3K, p110 alpha, p110 beta, and p110 delta, phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) into phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane. In cancer, these catalytic subunits are usually found to be altered or amplified. Because pan-PI3K inhibition results in systemic toxicities, finding specific targets for the ubiquitous PI3K isoforms offers considerable potential for enhancing the effectiveness of PI3K-targeted therapy. Methods We aim to delineate the isoform-specific druggable targets of the PI3K by deleting PIK3CA (encoding p110 alpha) and PIK3CB (encoding p110 beta) by Cre mediated excision and ectopically expressing p110 alpha, p110 beta, or p110 delta with or without myristoylation (Myr) tag in mouse embryonic fibroblasts (MEFs). Myr is a lipidation signal that translocates proteins to plasma membrane permanently. This translocation renders p110s constitutively activated as they remain in close proximity to PIP(2 )on the membrane. Results Unique and redundant Akt targets are identified downstream of different PI3K isoforms. mTORC1, one of the targets of fully-activated Akt, has been observed to be differentially regulated in MEFs upon expression of p110 alpha or p110 beta. The varying dependencies on mTORC1 and Rac1 led us to analyse a potential scaffolding function of p110 beta with Rac1 to mediate phosphorylation and activation of mTOR using platforms for the modeling of biomolecular complexes. We also documented that p110 alpha and p110 beta support cell cycle kinetics differentially. Conclusions This study suggests differential regulation of protein translation, metabolism, cell cycle, and survival signaling downstream of unique p110 targets, underlying the importance of cancer treatment according to the deregulated p110 isoform.Item 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.Item Open Access Cytotoxic activity of resveratrol in different cell lines evaluated by MTT and NRU assays(Turkish Pharmacists Association, 2016) Anlar, H. G.; Bacanli, M.; Kutluk, B.; Başaran, A. A.; Başaran, N.Oxidative stress is the state of imbalance between the level of antioxidant defence system and production of reactive oxygen species (ROS) and is involded in the progression of several diseases such as inflammation, cancer, neurodegenerative disorders and cardiovascular diseases. It is suggested that plant polyphenols may act as antioxidants and therefore it has anti-cancer activities. Resveratrol (RV), is a naturally occuring polyphenolic compound which is found in many plant species including grapes, nuts, blueberries and raspberries. Data indicated that it has anti-oxidant, anti-inflamatory and anti-cancer activities. But there are also some studies reported that RV has not protective effects aganist cancer. In this study, the cytotoxicity of RV in human breast adenocarcinoma (MDA-MB 231), human cervical cancer (HeLa) and Chinese hamster lung fibroblast (V79) cells were evaluated by Neutral Red uptake assay (NRU) and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays after incubation at 24 h. We obtained more or the less same results by two cytotoxicity assays. In the concentrations between 2-400 μM, RV seemed not to induce a pronounced cytotoxicity in all cell types. Even at highest concentrations, it showed almost no cytotoxic effects. So the IC50 values were not calculated at the studied concentrations.Item Open Access Cytotoxic and bioactive properties of different color tulip flowers and degradation kinetic of tulip flower anthocyanins(Pergamon Press, 2013) Sagdic, O.; Ekici, L.; Ozturk, I.; Tekinay, T.; Polat, B.; Tastemur, B.; Bayram, O.; Senturk, B.This study was conducted to determine the potential use of anthocyanin-based extracts (ABEs) of wasted tulip flowers as food/drug colorants. For this aim, wasted tulip flowers were samples and analyzed for their bioactive properties and cytotoxicity. Total phenolic contents of the extracts of the claret red (126.55. mg of gallic acid equivalent (GAE)/g dry extract) and orange-red (113.76. mg GAE/g dry extract) flowers were the higher than those of the other tulip flowers. Total anthocyanin levels of the violet, orange-red, claret red and pink tulip flower extracts were determined as 265.04, 236.49, 839.08 and 404.45. mg pelargonidin 3-glucoside/kg dry extract, respectively and these levels were higher than those of the other flowers. The extracts were more effective for the inhibition of Listeria monocytogenes, Staphylococcus aureus and Yersinia enterocolitica compared to other tested bacteria. Additionally, the cytotoxic effects of five different tulip flower extracts on human breast adenocarcinoma (MCF-7) cell line were investigated. The results showed that the orange red, pink and violet extracts had no cytotoxic activity against MCF-7 cell lines while yellow and claret red extracts appeared to be toxic for the cells. Overall, the extracts of tulip flowers with different colors possess remarkable bioactive and cytotoxic properties. © 2013 Elsevier Ltd.Item Open Access Cytotoxicity of multifunctional surfactant containing capped mesoporous silica nanoparticles(Royal Society of Chemistry, 2016) Yildirim, A.; Turkaydin, M.; Garipcan, B.; Bayındır, MehmetThis paper reports the synthesis of silica capped surfactant (cetyltrimethylammonium bromide; CTAB) and dye (Rose Bengal; RB) containing mesoporous silica nanoparticles (MSNs). Capping the pores of the surfactant containing MSNs with a thin silica layer decreased the immediate surfactant originated cytotoxicity of these particles without affecting their long term (3 days) cytotoxicity. Also, the silica capping process almost completely prevented the hemolytic activity of the surfactant containing MSNs. In addition, improved uptake of silica capped MSNs compared to the uncapped particles by cancer cells was demonstrated. The delayed cytotoxicity, low hemolytic activity, and better cellular uptake of the silica capped MSNs make them promising for the development of safe (i.e. with fewer side effects) yet efficient theranostic agents. These nanocarriers may release the loaded cytotoxic molecules (CTAB) mostly after being accumulated in the tumor site and cause so minimal damage to the normal tissues and blood components. In addition, the nanoscale confinement of RB molecules inside the pores of MSNs makes the particles brightly fluorescent. Furthermore, it was demonstrated that due to the singlet oxygen generation capability of the RB dye the silica capped MSNs can be also used for photodynamic therapy of cancer. © 2016 The Royal Society of Chemistry.Item Open Access Design, synthesis, and biological evaluation of indole-based 1,4-disubstituted piperazines as cytotoxic agents(2012) Akkoç Köksal, M.; Yüksel Yarım, M.; Durmaz, İrem; Atalay Çetin, RengülA series of 3-[(4-substitutedpiperazin-1-yl)methyl]-1H -indole derivatives were synthesized, and their structures were confirmed by spectral analysis. All the compounds were tested for their cytotoxic activity in vitro against 3 human tumor cell lines: human liver (HUH7), breast (MCF7), and colon (HCT116). Among the designed derivatives, most of the compounds showed significant cytotoxicity against liver and colon cancer cell lines with lower IC50 concentrations than the standard drug 5-fluorouracil. Compound 3s, with 3,4-dichlorophenyl substituent on the piperazine ring, was the most active in suppressing the growth of all screened cancer cells. © TÜBITAK.Item Open Access Enhanced sensitivity of colon tumour cells to natural killer cell cytotoxicity after mild thermal stress is regulated through HSF1-mediated expression of MICA(Taylor & Francis, 2013) Dayanc, B. E.; Bansal, S.; Gure, A. O.; Gollnick, S. O.; Repasky, E. A.Purpose: Previously we showed that mild thermal stress increased natural killer (NK) cell-mediated tumour cytotoxicity and that this could be blocked by anti-NKG2D or anti-MICA (major histolocompatability complex (MHC) class I related chain A) antibodies. Here, we investigated the role of the transcription factor heat shock factor 1 (HSF1) in thermal regulation of MICA expression in tumour cells in vitro and in vivo. Materials and methods: Hyperthermia experiments were conducted in vitro and in mice using a target temperature of 39.5 °C. Apoptotic cells and NK cells in situ were visualised by use of the TUNEL assay or expression of NKp46 respectively. Using Colo205 cells, HSF1 message was blocked utilising siRNA while luciferase reporter assays were used to measure the activity of the MICA promoter in vitro. Cell surface MICA was measured by flow cytometry. Results: Following whole body hyperthermia (WBH), tumour tissues showed an increase in NK cells and apoptosis. Mild thermal stress resulted in a transient increase in surface MICA and enhanced NK cytotoxicity of the Colo205 colon cancer cell line. Silencing (mRNA) HSF1 expression in Colo205 cells prevented the thermal enhancement of MICA message and surface protein levels, with partial loss of thermally enhanced NK cytotoxicity. Mutations of the HSF1 binding site on the MICA promoter implicated HSF1 in the thermal enhancement of MICA. Some, but not all, patient-derived colon tumour derived xenografts also exhibited an enhanced MICA message expression after WBH. Conclusions: Up-regulation of MICA expression in Colo205 cells and enhanced sensitivity to NK cell killing following mild thermal stress is dependent upon HSF1. © 2013 Informa UK Ltd.Item Open Access Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium(Elsevier, 2010) Erkekoglu, P.; Rachidi, W.; Yuzugullu, O. G.; Giray, B.; Favier, A.; Ozturk, M.; Hincal, F.Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of spermatogenesis in rodents, and Leydig cells are one of the main targets of phthalates' testicular toxicity. Selenium is known to be involved in the modulation of intracellular redox equilibrium, and plays a critical role in testis, sperm, and reproduction. This study was aimed to investigate the oxidative stress potential of DEHP and its consequences in testicular cells, and examine the possible protective effects of selenium using the MA-10 mouse Leydig tumor cell line as a model. In the presence and absence of selenium compounds [30. nM sodium selenite (SS), and 10 μM selenomethionine (SM)], the effects of exposure to DEHP and its main metabolite mono(2-ethylhexyl)-phthalate (MEHP) on the cell viability, enzymatic and non-enzymatic antioxidant status, ROS production, p53 expression, and DNA damage by alkaline Comet assay were investigated. The overall results of this study demonstrated the cytotoxicity and genotoxicity potential of DEHP, where MEHP was found to be more potent than the parent compound. SS and SM produced almost the same level of protection against antioxidant status modifying effects, ROS and p53 inducing potentials, and DNA damaging effects of the two phthalate derivatives. It was thus shown that DEHP produced oxidative stress in MA-10 cells, and selenium supplementation appeared to be an effective redox regulator in the experimental conditions used in this study, emphasizing the critical importance of the appropriate selenium status. © 2010 Elsevier Inc.Item Open Access Gemcitabine integrated nano-prodrug carrier system(American Chemical Society, 2017) Hamsici, S.; Ekiz, M. S.; Ciftci, G. C.; Tekinay, A. B.; Güler, Mustafa O.Peptide nanomaterials have received a great deal of interest in drug-delivery applications due to their biodegradability, biocompatibility, suitability for large-scale synthesis, high drug-loading capacities, targeting ability, and ordered structural organization. The covalent conjugation of drugs to peptide backbones results in prolonged circulation time and improved stability of drugs. Therapeutic efficacy of gemcitabine, which is used for breast cancer treatment, is severely compromised due to its rapid plasma degradation. Its hydrophilic nature poses a challenge for both its efficient encapsulation into nanocarrier systems and its sustained release property. Here, we designed a new peptide prodrug molecule for the anticancer drug gemcitabine, which was covalently conjugated to the C-terminal of 9-fluorenylmethoxy carbonyl (Fmoc)-protected glycine. The prodrug was further integrated into peptide nanocarrier system through noncovalent interactions. A pair of oppositely charged amyloid-inspired peptides (Fmoc-AIPs) were exploited as components of the drug-carrier system and self-assembled into one-dimensional nanofibers at physiological conditions. The gemcitabine integrated nanoprodrug carrier system exhibited slow release and reduced the cellular viability of 4T1 breast cancer cell line in a time- and concentration-dependent manner.Item Open Access Local delivery of doxorubicin through supramolecular peptide amphiphile nanofiber gels(Royal Society of Chemistry, 2017) Cinar, G.; Ozdemir, A.; Hamsici, S.; Gunay, G.; Dana, A.; Tekinay, A. B.; Güler, Mustafa O.Peptide amphiphiles (PAs) self-assemble into supramolecular nanofiber gels that provide a suitable environment for encapsulation of both hydrophobic and hydrophilic molecules. The PA gels have significant advantages for controlled delivery applications due to their high capacity to retain water, biocompatibility, and biodegradability. In this study, we demonstrate injectable supramolecular PA nanofiber gels for drug delivery applications. Doxorubicin (Dox), as a widely used chemotherapeutic drug for breast cancer treatment, was encapsulated within the PA gels prepared at different concentrations. Physical and chemical properties of the gels were characterized, and slow release of the Dox molecules through the supramolecular PA nanofiber gels was studied. In addition, the diffusion constants of the drug molecules within the PA nanofiber gels were estimated using fluorescence recovery after the photobleaching (FRAP) method. The PA nanofiber gels did not show any cytotoxicity and the encapsulation strategy enhanced the activity of drug molecules on cellular viability through prolonged release compared to direct administration under in vitro conditions. Moreover, the local in vivo injection of the Dox encapsulated PA nanofiber gels (Dox/PA) to the tumor site demonstrated the lowest tumor growth rate compared to the direct Dox injection and increased the apoptotic cells within the tumor tissue for local drug release through the PA nanofiber gels under in vivo conditions.Item Open Access Nanostructured materials for biological imaging and chemical sensing(Bilkent University, 2014-11) Yıldırım, AdemIn the recent years, the design and synthesis of fluorescent nanoparticles for biological and chemical sensing applications have received considerable attention due to the excellent photostability and emission intensity of fluorescent nanoparticles and the intrinsic sensitivity of fluorescence based methods. Although considerable progress has been made in their synthesis, there is still need for low-cost and high throughput methods for their widespread utilization in biological and chemical sensing applications. In addition, studies regarding their biocompatibility are necessary to identify the toxicological potential of these nanomaterials. In this context, this thesis seeks new methods for multifunctional fluorescent nanoparticle synthesis and investigates their interactions with living organisms. In addition, it reports the applications of the fluorescent nanomaterials in biological imaging, therapy and chemical sensing applications. First, we report a self-assembly method to prepare PEGylated or peptide functionalized mesoporous silica nanoparticles (MSNs) for cell labeling and drug delivery applications. The good cyto- and blood- compatibility of the functionalized nanoparticles were demonstrated. Next, we demonstrated a surfactant assisted method to synthesize ultrabright silica nanoparticles and studied their in vitro v cytocompatibility with several cell lines. We demonstrated the applications of ultrabright particles in cell labeling, chemo and photodynamic therapy and trace explosive sensing. Then, we discuss a template-free method (porosity difference based selective dissolution strategy) to prepare self-luminescent mesoporous hollow silica nanoparticles with tailored shapes. In addition, we studied the surface effects on blood compatibility of nanoparticles in detail using the MSNs possessing different surface functional groups (ionic, polar, neutral, and hydrophobic). Finally, we investigated the optical properties of polydopamine nanoparticles and showed that fluorescence of asprepared polydopamine nanoparticles can be used for sensitive and selective detection of the dopamine neurotransmitter.Item Open Access Predicting chemotherapy sensitivity profiles for breast cancer cell lines with and without stem cell-like features(Bentham Science Publishers B.V., 2013) Isbilen, M.; Senses, K. M.; Gure, A. O.Our current understanding of cancer-stem cells (CSCs) is that they are slow growing, generally mesenchymallike cells capable of generating tumors. Convincing evidence for the existence of such cells comes from recent lineage tracing experiments. CSCs have been reported as being resistant to conventional drug treatment and have been considered as being responsible for failure of chemotherapy. Recently, several databases aiming the genetic characterization of a large number of cancer cell lines have been made publicly available. In addition to gene expression data, these databases contain cytotoxicity information for all cell lines for a number of drugs as well. It is possible to classify known cell lines derived from a given tumor, based on how similar they are to CSCs, or in other words, to define their stem-ness, using gene-lists that define such cells. Using two such, independently generated, gene lists we found that breast cancer cell lines could be categorized into two distinct groups which we designate CSC-like and non-CSC-like. We then identified drugs to which the two groups were most sensitive to. We also generated sensitivity profiles for all drugs, within one such database, to identify chemotherapeutics with preferential action on breast cancer. We believe this is a straight-forward approach for swiftly identifying drugs that would selectively target a subpopulation of cells for any given tumor type. © 2013 Bentham Science Publishers.Item Open Access Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide(Public Library of Science, 2020) Türk, S.; Türk, C.; Akbar, Muhammad Waqas; Küçükkaraduman, Barış; İşbilen, Murat; Demirkol-Canlı, S.; Malkan, Ü. Y.; Okay, M.; Uçar, G.; Sayınalp, N.; Haznedaroğlu, İ. C.; Güre, Ali OsmayDespite the availability of various treatment protocols, response to therapy in patients with Acute Myeloid Leukemia (AML) remains largely unpredictable. Transcriptomic profiling studies have thus far revealed the presence of molecular subtypes of AML that are not accounted for by standard clinical parameters or by routinely used biomarkers. Such molecular subtypes of AML are predicted to vary in response to chemotherapy or targeted therapy. The Renin-Angiotensin System (RAS) is an important group of proteins that play a critical role in regulating blood pressure, vascular resistance and fluid/electrolyte balance. RAS pathway genes are also known to be present locally in tissues such as the bone marrow, where they play an important role in leukemic hematopoiesis. In this study, we asked if the RAS genes could be utilized to predict drug responses in patients with AML. We show that the combined in silico analysis of up to five RAS genes can reliably predict sensitivity to Doxorubicin as well as Etoposide in AML. The same genes could also predict sensitivity to Doxorubicin when tested in vitro. Additionally, gene set enrichment analysis revealed enrichment of TNF-alpha and type-I IFN response genes among sensitive, and TGF-beta and fibronectin related genes in resistant cancer cells. However, this does not seem to reflect an epithelial to mesenchymal transition per se. We also identified that RAS genes can stratify patients with AML into subtypes with distinct prognosis. Together, our results demonstrate that genes present in RAS are biomarkers for drug sensitivity and the prognostication of AML.Item Open Access Retinoid N-(1H-benzo[d]imidazol-2-yl)-5,5,8,8-tetramethyl-5,6,7, 8-tetrahydronaphthalene-2-carboxamide induces p21-dependent senescence in breast cancer cells(Elsevier, 2016) Mumcuoglu, M.; Gurkan-Alp, A. S.; Buyukbingol, E.; Cetin Atalay, R.Retinoids have been implicated as pharmacological agents for the prevention and treatment of various types of cancers, including breast cancers. We analyzed 27 newly synthesized retinoids for their bioactivity on breast, liver, and colon cancer cells. Majority of the retinoids demonstrated selective bioactivity on breast cancer cells. Retinoid 17 had a significant inhibitory activity (IC50 3.5 μM) only on breast cancer cells while no growth inhibition observed with liver and colon cancer cells. The breast cancer selective growth inhibitory action by retinoid 17 was defined as p21-dependent cell death, reminiscent of senescence, which is an indicator of targeted receptor mediated bioactivity. A comparative analysis of retinoid receptor gene expression levels in different breast cancer cells and IC50 values of 17 indicated the involvement of Retinoid X receptors in the cytotoxic bioactivity of retinoid 17 in the senescence associated cell death. Furthermore, siRNA knockdown studies with RXRγ induced decrease in cell proliferation. Therefore, we suggest that retinoid derivatives that target RXRγ, can be considered for breast cancer therapies. © 2016 Elsevier Inc. All rights reserved.Item Open Access A series of 2,4(1H,3H)-quinazolinedione derivatives: synthesis and biological evaluation as potential anticancer agents(Bentham Science Publishers, 2016) Akgün, H.; Us-Yılmaz, D.; Çetin-Atalay, Rengül; Gözen, DamlaA series of 6,7-disubstituted-3-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}quinazoline- 2,4(1H,3H)-dione derivatives (7-34) were synthesized and their structures were elucidated on the basis of analytical and spectral (UV, IR, 1H-NMR, 13C-NMR and MS) data. These synthesized compounds were evaluated for their in vitro cytotoxicities against a panel of three human cancer cell lines. According to the cytotoxicity screening results, 3-{2-[4-(4-chlorobenzyl)piperazin-1-yl]-2-oxoethyl} quinazoline-2,4(1H,3H)-dione (7) presented the highest activity against HUH-7, MCF-7 and HCT-116 cell line with the IC50 values of 2.5, 6.8 and 4.9 µM, respectively.Item 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.Item Open Access Synthesis and bio-molecular study of (+)-NAcetyl- α-amino acid dehydroabietylamine derivative for the selective therapy of hepatocellular carcinoma(BioMed Central Ltd., 2016) Mustufa, M. A.; Ozen, C.; Hashmi, I. A.; Aslam, A.; Baig, J. A.; Yildiz, G.; Muhammad, S.; Solangi, I. B.; Naqvi, Naim ul Hasan.; Ozturk, M.; Ali, F. I.Background: The purpose of present work is to synthesize novel (+)-Dehydroabietylamine derivatives (DAAD) using N-acetyl-α-amino acid conjugates and determine its cytotoxic effects on hepatocellular carcinoma cells. Methods: An analytical study was conducted to explore cytotoxic activity of DAAD on hepatocellular carcinoma cell lines. The cytotoxicity effect was recorded using sulforhodamine B technique. Cell cycle analysis was performed using Propidium Iodide (PI) staining. Based on cell morphology, anti growth activity and microarray findings of DAAD2 treatment, Comet assay, Annexin V/PI staining, Immunoperoxidase assay and western blots were performed accoringly. Results: Hep3B cells were found to be the most sensitive with IC50 of 2.00 ± 0.4 μM against (+)-N-(N-Acetyl-L-Cysteine)-dehydroabietylamine as DAAD2. In compliance to time dependent morphological changes of low cellular confluence, detachment and rounding of DAAD2 treated cells; noticeable changes in G2/M phase were recorded may be leading to cell cycle cessation. Up-regulation (5folds) of TUBA1A gene in Hep3B cells was determined in microarray experiments. Apoptotic mode of cell death was evaluated using standardized staining procedures including comet assay and annexin V/PI staining, Immuno-peroxidase assay. Using western blotting technique, caspase dependant apoptotic mode of cell death was recorded against Hep3B cell line. Conclusion: It is concluded that a novel DAAD2 with IC50 values less than 8 μM can induce massive cell attenuation following caspase dependent apoptotic cell death in Hep3B cells. Moreover, the corelation study indicated that DAAD2 may have vital influence on cell prolifration properties. © 2016 The Author(s).Item Open Access Synthesis and cytotoxicity studies of novel benzhydrylpiperazine carboxamide and thioamide derivatives(Informa Healthcare, 2014) Gurdal, E. E.; Durmaz, I.; Cetin Atalay, R.; Yarim, M.Synthesis and cytotoxic activities of 32 benzhydrylpiperazine derivatives with carboxamide and thioamide moieties 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. In general, 4-chlorobenzhydrylpiperazine derivatives were more cytotoxic than other compounds. In addition, thioamide derivatives (6a-g) have higher growth inhibition than their carboxamide analogs. © 2014 Informa UK Ltd. All rights reserved.