Digital Commons Network^™

Comparison Of Steriplex™ Hc And Sodium Hypochlorite Cytotoxicity On Primary Human Gingival Fibroblasts, Jesse Harris

Theses and Dissertations

This study examined the cytotoxic effects of STERIPLEX™ HC (sBioMed, Orem, UT) and sodium hypochlorite (NaOCl) on human fibroblast cells in vitro. Fibroblasts exposed to various concentrations of NaOCl or STERIPLEX™ HC were visualized via light microscopy. Dilutions of either NaOCl or STERIPLEX™ HC that did not appear to disrupt the integrity of the cells were recorded for further analysis. Cells were then cultured and grown to confluence in five separate plates. A void was created down the middle of each plate. If the cells were viable, cellular confluence was seen. If nonviable, confluence of the cells did not occur. …

1-Methoxy-Canthin-6-One And Related Β-Carbolines: From Natural Compound To Synthesis And Biological Activities (Abstract), Shiyou Li, Ping Wang

NCPC Publications and Patents

No abstract provided.

Cytotoxic And Antibacterial Activities Of Leaf Extracts Of Astragalus Gombiformis Pomel (Fabaceae) Growing Wild In Tunisia, Hassen Teyeb, Nahla Zanina, Mohamed Neffati, Wahiba Douki, Mohamed Fadhel Najjar

Turkish Journal of Biology

Many species of the genus Astragalus have been long used in folk medicine because of their biological properties. The aim of this study was to investigate the antibacterial and cytotoxic activities of extracts from the leaves of wild Astragalus gombiformis Pomel. Antibacterial activity was assayed against several common human pathogenic bacterial strains using the paper disk-agar diffusion method. Cytotoxicity was measured against human lung carcinoma cells using the colorimetric MTT assay. The strongest cytotoxic activity against the human A549 lung epithelial carcinoma cell line was detected for dichloromethane extracts at IC_{50} = 85 ± 21.7 µg/mL. The best incubation time …

Phytochemical Constituents And Pharmacological Activities Of Eryngium L.(Apiaceae), Ping Wang, Zushang Su, Wei Yuan, Guangrui Deng, Shiyou Li

Faculty Publications

Eryngium L. is the largest and arguably the most taxonomically complex genus of the family Apiaceae. The genus has approximately 250 species throughout the world, with the center of diversity in South America. Some Eryngium species are cultivated as ornamental, vegetable, or medicinal crops for folk uses. With increasing chemical and biological investigations, Eryngium has shown its potential as pharmaceutical crops. This review focuses on phytochemistry and pharmacological activities of 127 compounds isolated and identified from 23 species of Eryngium, particularly nonessential oil compounds such as terpenoids, triterpenoid saponins, flavonoids, coumarins, polyacetylenes, and steroids. Eryngium extracts or isolates have shown …

Design, Synthesis, And Biological Evaluation Of Indole-Based 1,4-Disubstituted Piperazines As Cytotoxic Agents, Meri̇ç Köksal Akkoç, Mi̇ne Yarim Yüksel, İrem Durmaz, Rengül Çeti̇n Atalay

Turkish Journal of Chemistry

A 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 IC_{50} 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.

Piper Betle Shows Antioxidant Activities, Inhibits Mcf-7 Cell Proliferation And Increases Activities Of Catalase And Superoxide Dismutase, N.N. Abrahim, M.S. Kanthimathi, A. Abdul-Aziz

Research Publications (2011 to 2015)

Background: Breast cancer is the most common form of cancer and the focus on finding chemotherapeutic agents have recently shifted to natural products. Piper betle is a medicinal plant with various biological activities. However, not much data is available on the anti-cancer effects of P. betle on breast cancer. Due to the current interest in the potential effects of antioxidants from natural products in breast cancer treatment, we investigated the antioxidant activities of the leaves of P. betle and its inhibitory effect on the proliferation of the breast cancer cell line, MCF-7.Methods: The leaves of P. betle were extracted with …

Assessment Of Carbon Nanoparticle Exposure On Murine Macrophage Function, Raquel M. Suro

Open Access Theses & Dissertations

There is growing concern about the potential cytotoxicity of nanoparticles. Exposure to respirable ultrafine particles (2.5uM) can adversely affect human health and have been implicated with episodes of increased respiratory diseases such as asthma and allergies. Nanoparticles are of particular interest because of their ability to penetrate into the lung and potentially elicit health effects triggering immune responses. Nanoparticles are structures and devises with length scales in the 1 to 100-nanometer range. Black carbon (BC) nanoparticles have been observed to be products of combustion, especially flame combustion and multi-walled carbon nanotubes (MWCNT) have been shown to be found in both …

Xanthones And Biphenyls From Garcinia Schomburgkiana Wood And Their Cytotoxicity, Chutichot Mungmee, Supotchana Sitthigool, Rutt Suttisri, Anumart Buakeaw

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Cytotoxic Evaluation Of The Powder Of Spinacia Oleracea In Human Liver Hepatocarcinoma Cell Line Using Mtt Assay, Sarunva Laovitthavanggoon, Krittiya Thisayakorn, Pongsathorn Limsiriwong, Sawai Nakakaew, Kanjana Sriyam, Vicheon Kaeynok, Chuleratana Banchonglikitkul

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

Cytotoxicity Of Gold Nanoparticles In Human Imr-32 Neuroblastoma Cells, Pokchat Lohaphansomboon, Pithi Chanvorachote, Warangkana Warisnoicharoen

The Thai Journal of Pharmaceutical Sciences

No abstract provided.

The Role Of Endoplasmic Reticulum Stress Response In Glioma Cell Death, Guyla G. Johnson

All ETDs from UAB

Malignant gliomas, including glioblastomas, are the main primary adult brain tumor. Even with current therapies, the median survival time for patients diagnosed with glioblastomas is only about 12 months. Therefore, it is imperative to identify pathways that can induce glioma cell death. This dissertation provides evidence defining how Endoplasmic Reticulum Stress Response (ERSR) induction promotes cell death selectively in malignant glioma cells (MGCs). I present data showing a correlation between ER Ca2+ storage abnormalities, ER ribosome-translocon expression and activity, ERSR intensity and cell death in MGCs. These data show ERSR induction with thapsigargin (THAP) results in a larger loss of …

Genotoxic Effects Of Banding Procedure With Different Orthodontic Cements On Human Oral Mucosa Cells, Firat Öztürk, Şengül Yüksel, Ebubeki̇r Toy, Elçi̇n Lati̇fe Kurtoğlu, Eyüp Burak Küçük

Turkish Journal of Medical Sciences

To assess the genotoxic and cytotoxic effects of banding procedure with 5 different orthodontic cements on human oral buccal epithelium cells. Materials and methods: Fifty healthy volunteers (mean age: 14.54 ± 2.37 years) were randomly divided into 5 groups of 10. Preformed stainless steel molar bands (3M Unitek) were cemented to the upper and lower first molar teeth with 5 different orthodontic cements (Durelon, GC Fuji Ortho Band LC Paste Pak, Meron, Ultra Band Lok, and 3M Unitek Multi Cure) in each group. Genotoxic effects of the banding procedure for a 1-month period were evaluated using the micronucleus test (MNT). …

Cytotoxicity Of Aloe Vera Gel Extracts On Allium Cepa Root Tip Cells, Ali̇ İrfan İlbaş, Umut Gönen, Semi̇h Yilmaz, Mehmet Yaşar Dadandi

Turkish Journal of Botany

Aloe vera L. is a valuable medicinal plant and is currently used in pharmaceutical, cosmetic, and food industries worldwide. In the present study, the effect of various concentrations of Aloe vera leaf gel extracts was investigated on mitotic and phase indexes of Allium cepa L. root tip cells for 24 and 48 h durations. The EC_{50} value of gel extracts was found to be 20% and was used to determine the experimental concentrations. The results indicated that the mitotic index and root growth rate of A. cepa were considerably decreased in comparison to the control. We found that the cytotoxic …

Cytotoxicity Evaluation Of Methacrylate-Based Resins For Clinical Endodontics In Vitro, Chul Ahn, Aniket S. Wadajkar, Qiang Zhu, Esteban G. Garza, Lynn A. Opperman, Larry L. Bellinger, Takashi Komabayashi

Bioengineering Faculty Publications - Archive

This study examines the cytotoxicity of Super-Bond C&B (SB-C&B), Super-Bond RC Sealer (SB-RC), MetaSEAL (Meta), and AH Plus Sealer (AH+). Freshly mixed and set materials (100 mg) were prepared in vitro and placed in cell culture medium (1 mL) for the working time and for 6 h, respectively. L929 cells seeded into 96-well plates at 5,000 cells/ well were incubated with the eluted medium (200 μL) for 24 h. Cells cultured with medium alone served as the control. Cytotoxicity was evaluated by MTS assay and analyzed with ANOVA. In the freshly mixed group, the average ± SD (%) for cell …

Syntheses And Characterization Of Water-Soluble Phythalocyanines For Diagnosis And Treatment Of Cancer, Benson Getenga Ongarora

LSU Doctoral Dissertations

Ongarora, Benson Getenga, B.S., Moi University, 2005 Doctor of Philosophy, Fall Commencement, 2012 Major: Chemistry Syntheses and Characterization of Water-Soluble Phthalocyanines for Diagnosis and Treatment of Cancer Dissertation directed by Professor M.Graҫa H. Vicente Pages in dissertation, xi. Words in abstract, 251. ABSTRACT Chapter 1 describes the general properties of phthalocyanines, synthesis of metallo-phthalocyanines, their photophysical features and their uses. The concepts of PDT and targeted therapeutics are also introduced. Chapter 2 describes the syntheses, characterization, photophysical studies and biological evaluation of cationic phthalocyanines. The trimethylaminophenoxy substituted phthalocyanines were synthesized through statistical condensation method, which gave a statistical mixture of …

Antimicrobial And Antiviral Effects Of Essential Oils From Selected Umbelliferae And Labiatae Plants And Individual Essential Oil Components, İlkay Erdoğan Orhan, Berri̇n Özçeli̇k, Murat Kartal, Yüksel Kan

Turkish Journal of Biology

The essential oils obtained from Anethum graveolens, Foeniculum vulgare collected at fully-mature and flowering stages, Mentha piperita, Mentha spicata, Lavandula officinalis, Ocimum basilicum (green- and purple-leaf varieties), Origanum onites, O. vulgare, O. munitiflorum, O. majorana, Rosmarinus officinalis, Salvia officinalis, and Satureja cuneifolia, as well as the widely encountered components in essential oils (\gamma-terpinene, 4-allylanisole, (-)-carvone, dihydrocarvone, D-limonene, (-)-phencone, cuminyl alcohol, cuminyl aldehyde, cuminol, trans-anethole, camphene, isoborneol, (-)-borneol, L-bornyl acetate, 2-decanol, 2-heptanol, methylheptane, farnesol, nerol, isopulegol, citral, citronellal, citronellol, geraniol, geranyl ester, linalool, linalyl oxide, linalyl ester, \alpha-pinene, \beta-pinene, piperitone, (-)-menthol, isomenthone, carvacrol, thymol, vanillin, and eugenol), were screened for their …

Cytotoxic Action Of Lead Nitrate On Cytomorphology Of Trigonella Foenum-Graecum L., Sana Choudhary, Mohammad Yunus Khalil Ansari, Zeba Khan, Honey Gupta

Turkish Journal of Biology

The present experiment was undertaken to determine the mutagenic potential of lead on the cytomorphology of Trigonella foenum-graecum L. and to determine the maximum concentration of lead nitrate that induces maximum genetic variability. The seeds were treated with 6 different concentrations (10, 25, 50, 100, 200, and 400 ppm) of lead nitrate. The higher concentrations of lead nitrate significantly reduced plant height, number of branches per plant, pollen fertility, and yield; higher concentrations also caused variation in the plants at the seedling and mature stages. In addition, concentrations affected the pairing of homologous chromosomes and spindle formation. This resulted in …

Antihyperglycemic, Antioxidant And Cytotoxic Activities Of Alocasia Macrorrhizos (Linn.) Rhizomes Extract, Md Masudur Rahman, Md. Aslam Hossain, Saiful Alam Siddique, Kaishar Parvej Biplab, Md. Helal Uddin

Turkish Journal of Biology

Alocasia macrorrhizos (L.) (Araceae), a coarse and erect plant that is widely cultivated to be eaten as a vegetable throughout Bangladesh, has been reported to possess a number of medicinal properties. The antihyperglycemic, antioxidant, and cytotoxic effects of the methanol extract of A. macrorrhizos rhizomes were investigated. The extract was given at a single dose (250 and 500 mg/kg) in alloxan-induced hyperglycemic mice. The extract at 500 mg/kg produced a significant (P < 0.05) decrease in the blood glucose level (55.49%) at 8 h of treatment when compared with the control and was comparable with the reference drug, metformin. The extract was also subjected to antioxidant potentiality and brine shrimp lethality bioassays. The IC_{50} value of the extract was 693.0 \mug/mL and the LC_{50} was 188.14 \mug/mL.

Design, Synthesis, And Anticancer Activity Of Ruthenium Complexes, Brock S. Howerton

Theses and Dissertations--Chemistry

Ruthenium complexes show promise as light activated photodynamic therapy (PDT) prodrugs. Strained octahedral complexes were synthesized that produce a cytotoxic species upon light activation. pUC19 DNA damage in vitro experiments were carried out to determine the type of damage observed. In vivo cell experiments were carried out on the non-small lung cancer A549 cell line to determine the phototherapeutic window of the synthesized complexes. One mechanism of drug resistance via elevated levels of glutathione was addressed through in vitro binding studies carried out with UV-Vis spectroscopy and in vivo glutathione titrations in the A549 cell line. Several complexes were shown …

Comparison Of Micro- And Nanoscale Fe+3-Containing (Hematite) Particles For Their Toxicological Properties In Human Lung Cells In Vitro, Kunal Bhattacharya, Eik Hoffmann, Roel Schins, Jens Boertz, Eva-Maria Prantl, Gerrit Alink, Hugh Byrne, Thomas Kuhlbusch, Qamar Rahman, Hartmut Wiggers, Christof Schulz, Elke Dopp

Articles

The specific properties of nanoscale particles, large surface-to-mass ratio and highly reactive surfaces, have increased their commercial application in many fields. However, the same properties are also important for the interaction and bio-accumulation of the non-/biodegradable nanoscale particles in a biological system and are a cause for concern. Hematite (α-Fe2O3), being a mineral form of Fe(III) oxide, is one of the most used iron oxides besides magnetite. The aim of our study was the characterization and comparison of biophysical reactivity and toxicological effects of α-Fe2O3 nano- (d < 100 nm) and microscale (d < 5 μm) particles in human lung cells. Our study demonstrates that the surface reactivity of nanoscale α-Fe2O3 differs to that of microscale particles with respect to the state of agglomeration, radical formation potential, and cellular toxicity. The presence of proteins in culture medium and agglomeration were found to affect the catalytic properties of the hematite nano- and microscale particles. Both the nano- and microscale α-Fe2O3 particles were actively taken up by human lung cells in vitro, although, they were not found in the nuclei and mitochondria. …

In Vitro Efficacy Of Hyperbaric Oxygen Therapy Against Leishmania Tropica Promastigotes And Amastigotes, Özgür Koru, Soykan Özkoç, Kemal Şi̇mşek, Gürkan Mert, Hakan Ay, Seray Töz, Mehmet Tanyüksel

Turkish Journal of Medical Sciences

Aim: To assess the efficiency of hyperbaric oxygen (HBO) therapy on L. tropica, which is the major causative agent of cutaneous leishmaniasis in Turkey. Materials and methods: The effects of HBO on Leishmania tropica promastigote and amastigote forms were studied at a pressure of 2.5 atmosphere absolute (ata). We examined the cytotoxic effect of HBO on promastigotes using the trypan blue exclusion test and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye-reduction assay. To investigate the effects of HBO treatment on the growth of the promastigotes, HBO-treated and non-HBO-treated cell culture flasks were incubated at 26 °C for 3 days, while the effects …

Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines, Breanne Landry

Pharmacy Faculty Articles and Research

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of …

Anticancer Effects Of Red Raspberries On Immune Cells And Blood Parameters, Jannet Romero

All Dissertations

There is an abundance of research correlating diets rich in fruits and vegetables to the reduction or prevention of chronic diseases such as cancer and cardiovascular disease. Plants extracts have also been claimed to possess antiviral, antibacterial, and immunological properties. This study focused on the in vitro and in vivo effects of a water extract from lyophilized Meeker red raspberries on tumor cell viability and immune parameters. A large number of studies have demonstrated the cytotoxic effect of different fruit juices and extracts against tumor cell lines in vitro. However, studies also show that the blood plasma levels of berry …

Ceacam1 Separates Graft-Versus-Host-Disease From Graft-Versus-Tumor Activity After Experimental Allogeneic Bone Marrow Transplantation., Sydney X Lu, Lucy W Kappel, Anne-Marie Charbonneau-Allard, Renée Atallah, Amanda M Holland, Claire Turbide, Vanessa M Hubbard, Jimmy A Rotolo, Marsinay Smith, David Suh, Christopher King, Uttam K Rao, Nury Yim, Johanne L Bautista, Robert R Jenq, Olaf Penack, Il-Kang Na, Chen Liu, George Murphy, Onder Alpdogan, Richard S Blumberg, Fernando Macian, Kathryn V Holmes, Nicole Beauchemin, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.

METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In …

In Vitro Cytotoxic Potential Of Swietenia Macrophylla King Seeds Against Human Carcinoma Cell Lines, B.H. Goh, A.H. Kadir

Research Publications (2011 to 2015)

Fruits of Swietenia macrophylla King (sky fruit) have been widely used in traditional medicine to treat various diseases including hypertension and diarrhea. The cytotoxic activity of the crude ethanol extract of the seeds of S. macrophylla and its fractions was assessed against selected human cancer cell lines, namely, HCT 116 (colon carcinoma), KB (nasopharyngeal epidermoid carcinoma), Ca Ski(cervical carcinoma) and MCF-7 (breast carcinoma) by using MTT assay. The S. macrophylla ethyl acetate fraction (SMEAF) showed the most potent activity against HCT116 cell line (IC50 = 35.35 μg/ml ± 0.50 ug/ml) in a dose- and time-dependent manner and was further investigated …

Impaired Memory Cd8 T-Cell Responses Against An Immunodominant Retroviral Cryptic Epitope, Melanie R. Rutkowski, Cynthia A. Stevens, William R. Green

Dartmouth Scholarship

The immunodominant cryptic epitope SYNTGRFPPL, encoded within open reading frame 2 of the LP-BM5 retroviral gag gene, is critical for protection against retroviral-induced pathogenesis. The goal of this study was to dissect the memory response against this unique immunodominant cryptic epitope. Unlike the protective acute effector population of SYNTGRFPPL-specific CD8 T cells, long-lived SYNTGRFPPL-specific CD8 T cells lacked the ability to protect susceptible mice infected with LP-BM5 retrovirus. Compared to memory CD8 T cells against a conventional epitope with similar MHC-I specificity, primed and restimulated using similar conditions, long-lived SYNTGRFPPL-specific CD8 T cells were impaired in their ability to recall …

Surface Functionalization Of Polymer Vesicles With Dendritic Groups: Effects On Physical And Biological Properties, Ryan C. Amos

Digitized Theses

Polymer vesicles (polymersomes) are spherical assemblies with aqueous cores, formed

by the self-assembly of amphiphilic polymers in an aqueous environment. They resemble

phospholipid vesicles, but typically exhibit much greater stabilities. The chemical versatility of

the polymer synthesis makes it possible to tune the vesicle characteristics such as vesicle size

and: circulation time in vivo. As such, they are highly promising materials for various

applications including drug delivery. Our research group recently developed a versatile approach

for the conjugation of dendritic groups to the surfaces of polymer vesicles which allows the

surface properties to be readily tuned for specific biological properties …

In Vitro Profiling Of Epigenetic Modifications Underlying Heavy Metal Toxicity Of Tungsten-Alloy And Its Components, Ranjana Verma, Xiufen Xu, Manoj K. Jaiswal, Cara Olsen, David Mears, Giuseppina Caretti, Zygmunt Galdzicki

Uniformed Services University of the Health Sciences

Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma(SKNMC), and mousemyoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50–200 μg/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calciumchannel …

Urginea Maritima (L.) Baker (Liliaceae) Extract Induces More Cytotoxicity Than Standard Chemotherapeutics In The A549 Non-Small Cell Lung Cancer (Nsclc) Cell Line, Hakan Bozcuk, Mustafa Özdoğan, Oktay Aykurt, Fati̇h Topçuoğlu, Hasan Öztürk, Deni̇z Eki̇nci̇, Asuman Karadeni̇z, Ayli̇n Mutlu, Durmuş Burgucu

Turkish Journal of Medical Sciences

Urginea maritima (Um) is a plant native to especially Turkey and the Mediterranean area. In this study, we investigated whether Um extract exerted cytotoxicity on cancer cells. Materials and methods: We made various extracts of Um. These extracts in varying concentrations were added to an A549 NSCLC cell culture, alone or with gemcitabine and/or cisplatin. Growth inhibition was tested by the MTT assay and an Annexin V-FITC apoptosis detection kit Results: The onion Um extract (1 µg/mL) was more cytotoxic than cisplatin (1 µg/mL), gemcitabine (1 nm/mL), and leaf Um extract (1 µg/mL) with P < 0.001, P = 0.097, and P < 0.001, respectively. The efficacy of Um extract was further improved by the addition of an antioxidant cocktail to an IC_{50} value of 0.02 µg/mL. Conclusion: Um extract has been shown for the first time to be a strong candidate for drug development in solid tumors. Our studies continue to further define the specific antitumor compound(s) in this extract.

Synthesis, Evaluation And Structural Studies Of Antiproliferative Tubulin-Targeting Azetidin-2-Ones, Niamh O'Boyle, Lisa M. Greene, Orla Bergin, Jean-Baptiste Fichet, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

A series of azetidin-2-ones substituted at positions 2, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerization that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the …