18^th International Conference on Medicinal Chemistry & Targeted Drug Delivery December 06-08, 2017 Dallas, USA

Biography:

Abstract:

Myokines are known to suppress some kinds of tumor. This fact makes it possible to explain the correlation between physical activities and cancer. The researcher suggests that Vimentin, an intermediate filament, is a novel myokine and has an anticancer effect on pancreatic cancer. Vimentin was shown to be secreted from muscle cells by muscle contraction. Furthermore, Vimentin treatment on L6 cell increased phosphorylation of AMPK and ACC. These results imply that Vimentin is associated with signaling pathways regulating various metabolisms. MTT assay results demonstrated that Vimentin controls the viability of pancreatic cancer cell, MIA-Pa-Ca-2. The study provides considerable insight into role of Vimentin as a myokine. Muscle contraction leads to secretion and Vimentin is involved in metabolism related to cancer. The evidence from this study also suggests that Vimentin could be used as a drug for cancer treatment. This study is the first step of developing a useful drug for cancer. 

Biography:

Hongli Wu has completed her PhD from Peking University and Postdoctoral studies from the University of Nebraska-Lincoln. She is the Assistant of Pharmaceutical Sciences at the University of North Texas Health Science Center. She has published more than 25 papers in reputable journals

Abstract:

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. The lack of adequate AMD animal models and poorly understood pathogenesis have greatly hindered our progress in therapeutic development. To address these shortcomings, this project was designed to examine how retinal redox dysregulation leads to AMD and characterize glutaredoxin 2 (Grx2), a mitochondrial thiol redox regulating enzyme, knockout mice as a new animal model for AMD. We found that Grx2 KO mice developed age-dependent retinal degenerative pathology. By 12-month of age, Grx2 null mice showed ~50% decrease in a-wave and ~30% decline in b-wave amplitude (n=8, P<0.01). Histological analysis revealed extensive RPE lesions, including RPE atrophy, vacuolation, hyper- and hypo-pigmentation, sub-RPE deposits, and loss of tight junction integrity. Age-dependent lipofuscin accumulation was also observed in Grx2 KO mice. Furthermore, Grx2 KO mice demonstrated increased marker of mitochondrial oxidative damage including PSSG accumulation. In conclusion, Grx2 plays a critical role in maintaining the mitochondrial redox homeostasis in the aging retina. Grx2 deficiency causes PSSG accumulation and sensitizes RPE cells to age-related oxidative damage, leading to RPE degeneration and photoreceptor damage. As a new animal model for AMD, Grx2 KO mice will provide new insights into pathogenesis and therapeutics of AMD. Grx2 may serve as a new therapeutic target for AMD and the Grx2 activating drugs may be used to treat AMD. 

Biography:

Jung-Mo Ahn has received his PhD in Chemistry from the University of Arizona and completed his Postdoctoral studies in the Scripps Research Institute. He is Associate Professor in Chemistry at the University of Texas at Dallas and a Council Member of the American Peptide Society. His research mainly focuses on structure-based design of peptidomimetics targeting protein-protein interactions.

Abstract:

Protein-protein interactions are one of the fundamental processes that regulate numerous key cellular pathways. Since α-helical structures are frequently found on the interfaces of protein complexes, short helical peptides derived from such proteins have been considered as a valuable tool for research and clinical applications. However, peptides in general may suffer from drawbacks that can severely compromise their effective in vivo use, such as rapid enzymatic degradation, poor bioavailability, and lack of membrane permeability. Thus, small molecules that mimic functions of helical peptides would be of great interest in targeting and disrupting protein-protein interactions that take place inside cells. To the end, we have designed oligo-benzamides as versatile scaffolds to emulate protein helical surfaces. The rigid oligo-benzamide scaffolds can present multiple functional groups corresponding to the side chains found on one helical face. In addition to the outstanding α-helix mimicry, oligo-benzamides can be efficiently synthesized by following high-yielding and iterative steps in solution- and solid-phase. Nuclear receptors like androgen receptor and estrogen receptor recruit a variety of coactivator proteins to exert their functions, and many of the molecular recognition are triggered by consensus LXXLL motifs. We have designed oligobenzamides based on the sequence and structure of the helical LXXLL motifs, and they demonstrated utilities in disrupting NR-coactivator protein complex formation, inhibiting NR-mediated gene transcription, and blocking NR-mediated cell proliferation in prostate and breast cancer cell lines. These exciting results indicate that oligo-benzamides are effective tools to mimic functions of α-helices and may have a high potential in biomedical research. 

Biography:

Adebayo A. Adeniyi is currently a postdoctoral fellow from the University of the Free State, South Africa and is also an academic lecturer at the University of Oye-Ekiti, Nigeria. He got his PhD in chemistry at University of Fort Hare, South Africa in 2014. He specializes in physical and computational chemistry but have a broad knowledge of all area of chemistry. His research interest is to combine both computational and experimental methods for the design of novel molecules for therapeutic application in order to circumvent the present limitations like drug resistance, mutation and adverse side effects in chemotherapy. He has published more than thirty research articles in pear review journals. He is a Nigerian citizen and a Christian by religion. He is married to Joy N. Adeniyi and is blessed with handsome boy called Daniel A.I. Adeniyi

Abstract:

The common cause of dementia among the elderly is known to be Alzheimer’s disease (AD) which is a disorder that results into a decline in progressive cognition and loss of memory due to the degeneration of the central nervous system. The compound HEX has been reported to show strong inhibitory activities against AChE than PHE and a very high selectivity for enzyme AChE over the enzyme BChE when compare to PHE (174-fold). The interest of this study is therefore use for classical molecular dynamic methods (CMD) and accelerated molecular dynamics (AMD) to give further insight into the selectivity of the HEX than PHE in their interaction with both AChE and BchE. High similarity in the RMSD of the two ligands with both AChE and BChE during the CMD and AMD trajectory were observed. Towards the end of the 20ns simulation of the AMD trajectory, the ligand HER seams to imposed new conformational change that resulted into its higher RMSD compare to the ligand PHR in both their interaction with AChE and BChE. As expected, a higher value of the RMSD was recorded for the AMD trajectory compare to CMD which is an indication of a greater number of conformational changes in the protein during the AMD. Our results show that the possible factors that contributes to the lower binding energy of PHE compare to HER especially in their interaction with AChE is as a result of penalizing effects of the generalized born solvent (ΔEegb), poisson boltzmann solvent (ΔEepb) and free energy of solvation (ΔGsolv).

Biography:

Xiaowei Dong received a BS in Industrial Analysis and a MS in Applied Chemistry from the universities in China, and a PhD in Pharmaceutical Sciences from the University of Kentucky. She was selected as one of six students nationwide to participate in the 2008 AAPS Graduate Student Symposium in Drug Delivery and Pharmaceutical Technology. She has worked as a Lead Formulator for drug development at Novartis Pharmaceutical Corporation for four years. In 2013, she has joined UNT Health Science Center as an Assistant Professor in the Department of Pharmaceutical Sciences at the College of Pharmacy. Her research has focused on drug delivery and formulation development. 

Abstract:

Oral dosage forms are the most common for medications. Optimization of bioavailability of orally administered drugs is one of the most important aims for pharmaceutical research. Solubility and permeability are two keys to achieve adequate oral bioavailability. The current target-based drug discovery approaches have tendency to drug-like compounds with poor solubility and/or poor permeability. Low bioavailability and inter- and intra-subject variability is often associated with these drugs because of their poor intestinal permeation and absorption. Thus, it is critical to develop novel formulation technologies to improve bioavailability for these drugs. Lipid nanoparticles or formulations have great potential to improve bioavailability of poorly water-soluble drugs by solving solubility issues. However, oral delivery of lipid formulations is limited because of the issues on stability, manufacturing and storage attributed to their liquid nature. Recently, we successfully developed the novel nanotechnology platform that applies the benefit of lipid nanoparticle for oral solid dosage forms. In this nanotechnology, we prepare solid granules that produces in situ self-assembly nanoparticles (ISNPs) when the granules are introduced to water with gentle agitation. The ISNP nanotechnology is not only scientifically novel, but also behaviorally superior to other existing technologies. The manufacturing of ISNP granules is very simple and scalable. We dramatically increased drug loading to 16% and bioavailability over 2.3-fold compared to commercial tablets by using the ISNP nanotechnology. Furthermore, the ISNP granules masked the bad taste of drugs. Thus, this novel ISNP nanotechnology has great potential for widespread applications to formulate poorly water-soluble and/or poorly permeable drugs in oral solid dosage forms. All these advances of the ISNP nanotechnology could significantly inspire and contribute to other novel applications of lipid-based excipients and/ or formulations in the field.