Thursday, February 5, 2015, 6:00 PM (The LI-ACS Seminar)
Dr. Tony Taldone (Memorial Sloan Kettering Cancer Center)
Discovery and Development of Purine-scaffold Hsp90 inhibitors for the Treatment of Cancer
Heat shock protein 90 (Hsp90) is a molecular chaperone exploited by cancer cells to aid in their survival. The recognition of Hsp90 as a critical facilitator for oncogene addiction and survival of cancer cells has opened a promising new niche for cancer treatment. The serendipitous discovery that the broad spectrum anticancer activity of the natural products geldanamycin (GM) and radicicol (RD) was a result of inhibition of Hsp90 resulted in the development of improved derivatives of these natural products. One of these was 17-AAG, a closely related analog of GM, and was in fact the first Hsp90 inhibitor to enter the clinic. However, GM and its analogs suffer from poor 'drug-like' properties and this served as a strong impetus for the development of novel synthetic Hsp90 inhibitors. One class to exhibit enhanced potency and improved pharmacokinetic properties is the purine-scaffold. A number of small-molecule Hsp90 inhibitors based on the purine-scaffold are currently being evaluated in clinical trials for cancer. Here, I will discuss their initial discovery and development into potential anticancer agents.
Thursday, March 5, 2015, 6:00 PM (The LI-ACS Seminar)
Dr. Ling Huang (Hofstra University)
'Spice Tales': Rapid Detection and Quantification of Synthetic Cannabinoids
Since 2008, Designer drugs such as synthetic cannabinoids mixed with herbal products, also known as ’Spice’ have been sold as herbal incenses in smoke shops and online. Many synthetic cannabinoids have been outlawed as Schedule I controlled substance. New and 'legal’ compounds are still being sold around the world, which creates challenges to forensic analysts and law enforcement agencies and causes great harm to unaware users. Our lab successfully utilizes NMR as an alternative to conventional GC-MS method to rapidly identify and quantify emerging cannabinoids. We have also optimized simple extraction technique for these designer herbal drugs prior to optimized HPLC separation and quantification. Our methods can be utilized to accelerate the accurate screening of designer drugs and to reduce evidence backlog in the battle with emerging ’Spice’ products.
Friday, March 13, 2015, 1:00 PM
Prof. Lissette Delgado-Cruzata (John Jay College of Criminal Justice)
DNA methylation, an epigenetic modification, tells us about tissues, lifestyle and disease
Epigenetics refers to heritable modifications that determine a change in gene expression, without modifications to the DNA. Originally discovered as an important mechanism in development and tissue differentiation, today we know that epigenetics is very important in the etiology of several chronic diseases. The best known epigenetic modification is the addition of a methyl group to the position 5 of a cytosine when it is next to a guanine, a CpG dinucleotide, and it is called DNA methylation. As it plays a role in the regulation of gene expression, DNA methylation is essential to all cellular processes and its alterations can change cell functioning. It is believed that epigenetic marks can be passed on from parents to offspring, but are also affected by lifestyle factors; which make them modifiable opening a wealth of applications to our understanding of its distribution and regulation. Since they are not determined by the DNA sequence, DNA methylation patterns can identify twins and have the potential to be used in forensic investigations involving them. As tissue patterns also exist, the unknown origin of a sample can also be determined using epigenetic targeting. In chronic diseases, such as cancer, aberrant DNA methylation is frequently found in tumor tissues of different types, and it has been identified as an early event in carcinogenesis of malignancies of among other organs, breast. Altered DNA methylation in blood has been found to be a marker of high breast cancer risk, and can possibly increase our knowledge of susceptibility to this disease.
Thursday, April 3, 2015, 6:00 PM (The LI-ACS Seminar)
Dr. Yu Chen (Queens College, CUNY)
Electrophilic Cyclizations of Alkynes-Facile Approaches to Heterocyclic and Carbocyclic Molecules
Palladium and gold-catalyzed as well as iodine monochloride-induced intramolecular electrophilic cyclizations of functionally substituted alkynes will be discussed. These regioselective annulations represent new and efficient synthetic approaches to carbocyclic and heterocyclic molecules, including isoxazoles, isoquinolines, indenones, and dibenzoannulen-5-ones. These approaches utilize palladium or gold catalyzed reactions as the key steps towards the production of the final target molecules or intermediate compounds. The new methods start from readily available starting materials and only consist of facile and user-friendly synthetic conditions, while they will serve as valuable tools for the preparation of compounds covering a broad spectrum of fields including synthetic and medicinal chemistry, and the material sciences.