Contacts:
Tel: +39-3913821437, +91-9981346205
e-mail: vibhu.jha@farm.unipi.it, vibhujha16@gmail.com
Supervisor:
Prof. Tiziano Tuccinardi
PhD project Title:
Computational approaches to identify small molecule modulators of new drug targets
Research summary:
My PhD research areas majorly involve computational drug discovery with an additional application of synthetic medicinal chemistry. I utilize in-silico guided approaches to identify new ligands as potential inhibitors of pharmacological target of our interest, with a great focus on investigation of anticancer hit compounds. I employ pharmacophore-based/ligand-based Virtual Screening (VS) procedures with of aid of molecular docking programs and post-docking refinement filters like Consensus Docking (CD) platform, Interaction-Fingerprints (IFP) and Molecular Dynamics (MD) simulations. The computational protocol also comprises of correct ligand-binding mode prediction and binding energetics studies to help in the hit identification and hit-lead optimisation workflow. First 17 months of my PhD (Nov. 2017- March 2019) were focussed on VS studies to identify hit inhibitors of following three important anticancer targets;
[1] Lactate dehydrogenase-A (LDH-A)
[2] Mono-acyl glycerol lipase (MAGL)
[3] StAR related lipid transfer domain containing 3 (STARD3)
The active compounds identified after enzyme assay were utilized for the improvement of previous VS study or subjected to synthetic optimisation by collaborative research groups.
From April-Sept 2019, I carried out synthetic medicinal chemistry project at Institute of Cancer Therapeutics (ICT), University of Braford, UK as a visiting PhD student under the supervision of Prof. Klaus Pors (Senior Lecturer, Chemical Biology). I was involved in design, synthesis, molecular docking and fluorescence tracking of Hypoxia-Activated Prodrugs (HAPs) as DNA intercalators against cancer cells. The synthesized compounds were tested against various cancer cell lines, active compounds were subjected to synthetic optimisation in order to lengthen the library of compounds. Compounds with notable fluorescence were further explored for clinical biomarker application.
Utilizing significant learning aspects from both computational drug discovery and synthetic medicinal chemistry research, remaining part of my PhD will be focussed on VS and medicinal chemistry projects for hit identification/hit-lead optimization of new and unexplored important biological targets.
Publications:
Poster communications at congress:
Jha V., Tuccinardi T., Granchi C., Minutolo F. Virtual screening platform on structure-based pharmacophore hypothesis to identify potential human LDH-A inhibitors against cancer. Italian-Spanish-Portuguese Joint Meeting in Medicinal Chemistry, MedChemSicily, University of Palermo, 2018, July17-20, Palermo, Italy.