Department of Medicinal Chemistry

[Site under construction]

• The role of halogen bonding in interaction of ligands with SERT., Jakub Staroń, PhD
  The  aim  of  this  study  is  to  investigate the  role  of  halogen  bonds  (XB) in  binding  ligands  to serotonin
  transporter (SERT) and their influence on ligand selectivity over other receptors, in particular 5-HT6R and 5-HT7R. The basic scientific question in this project is: “Is it possible to increase ligand affinity to SERT by
  careful  design  and  introduction  of  a  halogen  bond  donor  into  ligand  structure?”. Additional  goal  is  the
  verification  of  hypothesis  that  appropriate  design  of  a  molecule  possessing  halogen  bond  donor(s)  it  is
  possible to create polypharmacological  molecule  with affinity for SERT and/or 5-HT6R, 5-HT7R. 5-HT6R
  and 5-HT7R were selected as additional targets as they were recently recognized as a very promising targets
  for  new  antidepressant  therapeutics  possessing  procognitive  properties.  To  the  best  of  our  knowledge
  substance simultaneously exhibiting affinity for SERT and 5-HT6R has never been reported before.
  
• Development of protocol for in silico design of compounds inhibit Ebola virus infection, Dawid Warszycki, PhD
  Research project objectives/hypothesisThe primary scientific objective of this project is to develop a protocol for the in silico design of inhibitors of Niemann-Pick type C1 protein (NPC1). The quintessence of this research is to create a virtual screening (VS) protocol that permits the prioritization of chemical compounds based on their potential inhibitory activity against NPC1 (a protein playing a crucial function in the process of Ebola virus infection). The application and improvement of the existing conceptual methodology targeting NPC1 inhibitors will allow broad exploration of the chemical space in search of new antiviral agents.Research methodologyThe screening cascade will consist of several subsequent steps (prefiltering, pharmacophore mapping, docking protocol, ADMETox filter, clustering, visual inspection) to select the most valuable structures. Each stage of the cascade will be created using procedures developed at the Department of Medicinal Chemistry. In the planned tasks, the following methodologies will be upgraded and applied: descriptors calculations and analyses, pharmacophore modeling, homology modeling and docking protocols. The VS protocol will be used to evaluate a virtual combinatorial library of compounds (created within the project) and to select compounds for synthesis (in independent projects initiated in the Institute of Organic Chemistry and Analytical Chemistry in Orleans, France) of the most promising structures.Research project impactThe realization of this project will create opportunities to establish structural requirements for compounds with potency to function as new antiviral agents that target one of the most dangerous viruses. The obtained VS protocol can be used multiple times both in commercial and virtual compound libraries. Moreover, this project will strengthen scientific cooperation between the Department of Medicinal Chemistry and the Institute of Organic Chemistry and Analytical Chemistry initiated several years ago. Positive results of this project may result in additional joint applications to extend the issues undertaken herein.At least one scientific publication in a journal from the Master Journal List will be the notable effects of the research. It has to be stressed, however, that depending on how many different groups of NPC1 inhibitors will be further developed in Orleans more publications are highly probable. In addition, the results will be presented at both international and national conferences. The implementation of this program will also enhance the experience of the candidate in the management of independent scientific projects.