Research
A large portion of today's major drugs have their origins in nature, plants, bacteria, fungi, marine organisms and other living creatures. Therefore, it is not surprising that one of the most flourishing and rewarding frontiers in modern science is the study of the chemistry and biology of natural products.
Not surprisingly, natural products with unusual structures often play an important role in the discovery of new, highly sophisticated, biological mechanisms of action, while, at the same time, they point out limitations of the current chemical synthesis art.
Thankfully, man's imagination does not stop at the frontiers defined by nature. A chemist’s ability to design and synthesize new molecules brings forward tools of enormous power for the molecular level investigations in many areas of science. In pursuing the total synthesis of natural products, new synthetic strategies and methodologies are invented to address the arising difficulties, and they remain afterwards as enabling technologies for chemistry, biology and medicine. The synthetic organic chemist of our times is destined to make important contributions through the development of new enabling technologies for the design and the generation of novel chemical entities of not only natural products, but also of designed small organic molecules of broad structural diversity for binding to and modulating the function of biological targets.
Our laboratory represents a new function within the Institute of Physical Chemistry, namely the “Chemical Biology of Natural Products and Designed Molecules”, which was initiated in July 2005 and our studies incorporate molecular design and analysis, total synthesis, structure/activity relationship observations, combinatorial synthesis and biological investigations. Our research focuses in the study of biological systems, DNA, RNA and proteins, through their interaction with small molecules of natural or synthetic origin, targeting the development of new and improved pharmaceutical entities. Our goal is the total synthesis of natural products and designed analogs with improved potencies and pharmacological profiles, the development of new synthetic methodologies in solution and solid phase and the development of new in vitro biological assays for the evaluation of the new synthetic entities. Our design will be based on crystallographic information and molecular modeling studies. Currently, we are involved in the areas of Cancer (topoisomerase II inhibitors, apoptosis), bacterial infections (aminoglycosides and A-site ribosomal-RNA) and anti-virals (Hepatitis C virus, HIV). Some of our ongoing projects are described bellow in more detail.
