Peter Peng Foo Lee

Copper, gold and silver compounds as potential new anti-tumor metallodrugs

Although platinum-based drugs such as cisplatin are powerful anticancer agents, they have undesirable side effects and are effective against only a few kinds of cancers. There is, therefore, a need for new drugs with an improved spectrum of efficacy and lower toxicity. Complexes of copper, gold and silver (coinage metals) are potential candidates to fulfill this need. The development of anticancer drugs based on these metals is currently a very active field. Considerable effort has also been put into elucidating the mechanisms of action of these complexes and optimizing their bioactivity through structural modification. In this review, we highlight recent developments in the design of coinage metal complexes with anti-tumor activity and discuss the emerging importance of quantitative structure-activity relationship methods in the study of anticancer metal complexes. Future work in this field, including likely coinage metal complexes that will attract attention, are proposed.

Validation of an ELISA test kit for the detection of ochratoxin A in several food commodities by comparison with HPLC.

An ELISA Microtiter Plate, Ochratoxin Test called AgraQuant® was validated to measure ochratoxin A in a range from 2 to 40 ppb in corn, milo, barley, wheat, soybeans and green coffee. The test is performed as a solid phase direct competitive ELISA using a horseradish peroxidase conjugate as the competing, measurable entity. For the test method, ochratoxin A is extracted from ground samples with 70% methanol and sample extracts plus conjugate are mixed and then added to the antibody-coated microwells. After 10 min incubation at room temperature, the plate is washed and enzyme substrate is added and allowed to incubate for an additional 5 min. Stop solution is then added and the intensity of the resulting yellow color is measured optically with a microplate reader at 450 nm. Results obtained from internal validation studies assessing accelerated stability indicate a 1 year shelf life; accuracy and precision are comparable to HPLC from 0 to 80 ppb and limit of detection in corn is 1.9 ppb and other food commodities is up to 3.8 ppb. Comparison of the method to HPLC, ability to detect individual ochratoxins, and ruggedness of the test kits determined this test to be rugged from 18 to 30 °C, sensitive, accurate, precise and effective comparable to HPLC for measuring ochratoxin A ranging from 2 to 40 ppb in several commodities.

Hantupeptin A, a cytotoxic cyclic depsipeptide from a Singapore collection of Lyngbya majuscula.

Chemical investigation of the marine cyanobacterium Lyngbya majuscula from Pulau Hantu Besar, Singapore, has led to the isolation of a cyclodepsipeptide, hantupeptin A (1). The planar structure of 1 was assigned on the basis of extensive 1D and 2D NMR spectroscopic experiments. The absolute configuration of the amino and hydroxyl acid residues in the molecule was determined by application of the advanced Marfey method, chiral HPLC analysis, and Moshers method. Hantupeptin A showed cytotoxicity to MOLT-4 leukemia cells and MCF-7 breast cancer cells with IC(50) values of 32 and 4.0 microM, respectively.

Synthesis and cytotoxic activities of chloropyridylimineplatinum(II) and chloropyridyliminecopper(II) surface-functionalized poly(amidoamine) dendrimers.

The preparations of novel platinum and copper metallodendrimers are reported. Surface modified first generation (G0) poly(amidoamine) (PAMAM) dendritic Schiff base, prepared via a condensation reaction was coordinated with platinum chloride and copper chloride yielding [G0-Py(4)-[PtCl(2)](4)] (4D) and [G0-Py(4)-[CuCl(2)](7)] (7E) respectively. These functionalized hyper-branched complexes were characterized by IR spectroscopy and CHN analysis. 4D was further characterized through (1)H and (13)C spectroscopy, while 7E was characterized using matrix-assisted laser desorption ionization time-of-flight (MALDI/TOF) Mass Spectrometer. The cytotoxic effects of the compounds against cells of neoplastic origin (MOLT-4, MCF-7) and cells of benign origin (Chang Liver) were studied. Their cytotoxicities were then compared to their mono-nuclear analogues, [(MeCONHCH(2)CH(2)NCHPy)(PtCl(2))] (1D) and [(MeCONHCH(2)CH(2)NCHPy)(CuCl(2))] (1E). The multi-nuclear complexes showed increased cytotoxic activities as compared to their respective mono-nuclear compounds. Most notably, significant inhibitions were observed for 7E on all cell lines, in which its IC(50) values were 11.1+/-0.6, 10.2+/-1.5 and 8.7+/-0.7microM against MOLT-4, MCF-7 and Chang Liver cells respectively. The multi-nuclear copper-based complexes (7E) are therefore most effective against a cancer cell line (MOLT-4) and a cisplatin-resistant cell line (MCF-7).

Hantupeptins B and C, cytotoxic cyclodepsipeptides from the marine cyanobacterium Lyngbya majuscula

Hantupeptins B (2) and C (3) were isolated, along with the previously reported hantupeptin A (1), from the marine cyanobacterium, Lyngbya majuscula, collected from Pulau Hantu Besar, Singapore. Their structures were elucidated by interpretation of extensive 1D and 2D NMR spectroscopic data. Compounds 2 and 3 are cyclic depsipeptides consisting of five alpha-amino/hydroxy acid residues, including phenyllactic acid, proline, N-methyl-valine, valine, N-methyl-isoleucine, and a beta-hydroxy acid unit with different degrees of unsaturation at the terminal end of each molecule. The absolute configurations of the common amino acids and phenyllactic acid were determined by the advanced Marfeys and chiral HPLC analyses, respectively. The complete stereochemistry of 3-hydroxy-2-methyl-7-octynoic acid moiety in hantupeptin A was elucidated by a combination of homonuclear J-resolved 2D NMR experiments and by Moshers method. Hantupeptins B and C showed moderate in vitro cytotoxicity when tested against MOLT-4 (leukemic) and MCF-7 (breast cancer) cell lines.

Rhenium(I) tricarbonyl complexes of salicylaldehyde semicarbazones: synthesis, crystal structures and cytotoxicity.

A series of N,N-disubstituted salicylaldehyde semicarbazones (SSCs), HOC(6)H(4)CHN-NHCONR(2), and their rhenium(I) tricarbonyl complexes, [ReBr(CO)(3)(SSC)], have been synthesised and characterised by IR and (1)H NMR spectroscopy. Crystallographic analysis of the complex [ReBr(CO)(3)(H(2)Bu(2))] (H(2)Bu(2)=SSC where R=Bu(n)) showed that the SSC acts as a bidentate ligand via its imino nitrogen and carbonyl oxygen atoms. The [ReBr(CO)(3)(SSC)] complexes exhibit moderate to high cytotoxicities towards MOLT-4 cells (IC(50)=1-24μM, cf. 18μM for cisplatin), and the majority of them are virtually non-toxic against non-cancerous human fibroblasts. Apoptotic assays of [ReBr(CO)(3)(H(2)Bnz(2))] (Bnz=benzyl) revealed that it mediates cytotoxicity in MOLT-4 cells via apoptosis. The complex [ReBr(CO)(3)(H(2)Bnz(2))] reacts with guanosine by proton transfer from the phenolic OH group to N(7) of guanosine. In (CD(3))(2)SO, [ReBr(CO)(3)(H(2)Bnz(2))] undergoes facile conversion to the dimeric complex, [Re(CO)(3)(HBnz(2))](2), via bromide dissociation.

Organic Solvent–Free Direct Asymmetric Aldol Reactions Catalyzed by a Siloxy Serine Organocatalyst in Brine

Abstract A siloxy serine organocatalyst has been developed to catalyze direct asymmetric aldol reactions in aqueous saline media. The asymmetric aldol reactions between a selection of aromatic aldehydes and cyclohexanone afforded the products in good yields and enantioselectivities (up to 92% ee).

Multiarray cell stretching platform for high-magnification real-time imaging.

AIM This article reports the development of a multiarray microchip with real-time imaging capability to apply mechanical strains onto monolayered cell cultures. MATERIALS & METHODS Cells were cultured on an 8-µm thick membrane that was positioned in the microscope focal plane throughout the stretching process. Each stretching unit was assembled from three elastomeric layers and a glass coverslip. A programmable pneumatic control system was developed to actuate this platform. Multiple stretching experiments were conducted with various cell lines. RESULTS The platform provides a maximum uniform strain of 69%. Acute and long-term cell morphological changes were observed. The supreme imaging capability was verified by real-time imaging of transfected COS-7 stretching and poststretching imaging of immunofluorescence-stained PTK2. CONCLUSION The platform reported here is a powerful tool for studying mechanically induced physiological changes in cells. Such a device could be used in tissue regeneration for maintaining essential cell growth conditions.

Educating science teachers in the 21st century: Implications for pre-service teacher education

Abstract This study examines the verbal interactions among a group of pre-service teachers as they engaged in scientific discussions in a medicinal chemistry course. These discussions were part of the course that encompassed an explicit instruction of scientific argumentation structures as well as an applied component, whereby the pre-service teachers learned the content of medicinal chemistry through cases developed using the strategy of competing theories. By adopting a case study approach using sociocultural framework of learning, we examined the interactions between the pre-service teachers using video data. We describe 12 possible forms of interactions during discussions – (1) seeking clarification, (2) figuring out loud, (3) sharing information, (4) agreement, (5) asking questions, (6) providing explanations, (7) raising strategic and procedural issues, (8) stating claims, (9) disagreement, (10) sharing perspectives, (11) offering alternatives, and (12) persuasion. The pre-service teachers engaged in figuring out aloud and seeking clarifications frequently, and used persuasion least in their discussions. To clarify their ideas and thoughts, pre-service teachers commonly rebut their counterparts and used warrants to support their own assertions. A similar pattern was also observed when figuring their thoughts out loud. Our findings suggest that pre-service teachers were able to carry out rebuttals in the argumentation process. However, the quality and function of their rebuttals can be improved by deepening their understanding of the subject matter knowledge and the science argumentation structure. Implications are discussed.