Research Fellow (RTD/A) at the University of Molise, Italy
Master Degree in Chemistry at the University of Naples “Federico II”, Italy.
PhD in Pharmaceutical Sciences at the University of Salerno, Italy.
Research and awards:
- Royal Society of Chemistry HOT Article Award (2020) for the paper “Accelerating the repurposing of FDA-approved drugs against coronavirus disease-19 (COVID-19)” DOI: https://doi.org/10.1039/D0RA09010G.
- “Giacomo Giamician Medal” (2016) received from the Italian Chemical Society (Organic Chemistry Division), an important prize given to young emerging researchers with age below 35 for outstanding contributions to the field of Organic Chemistry, for: “her contributions to the development of combined methods of computational chemistry and NMR applied to structural studies and ligand-receptor integrations, to design and identify new active molecules with anticancer and anti-inflammatory properties”
- “Giacomino Randazzo Prize”(2013) awarded by The Italian Chemical Society, Division of Organic Chemistry, for a Ph.D. thesis entitled “Design, virtual screening and structural studies of new molecules with potential antitumor and anti-inflammatory activity”.
Her research activity was mainly focused on the study of ligand-receptor interactions and structural characterization by computational techniques and NMR spectroscopy to identify new antitumor and anti-inflammatory molecules potentially utilizable in therapy. Furthermore, to improve her knowledge of methodologies for the stereostructural assignment, she moved to the Department of Chemistry of the Bristol University in 2011 under the supervision of Prof. Craig Butts.
During this period, her research work in this period has included learning and conducting advanced NMR spectroscopic investigations of a number of natural products, contributing to the development combined accurate ROE-distance analysis with DFT calculations of NMR chemical shifts to achieve the relative configuration assignment of a marine natural product (see ref.15 in the publications list).
In addition to Ph.D. course activities, she was involved in different side projects, mainly regarding the characterization of ligand-targets interactions of ligands on targets involved in other pathologies as e.g. Alzheimer (see ref. 3) and obesity (see ref. 24).
In particular, her research projects can be summarized in three main areas:
a) Support in the design of original scaffolds for the generation of libraries potentially utilizable in therapy. This work was exclusively conducted in silico by a molecular docking technique to direct the design of the new molecules is basing on the analysis of ligand-target interactions and the synthetic possibilities. This kind of approach was successfully applied leading to the identification of new potential inhibitors for HDAC enzymes (e.g. see ref. 1) with cyclic (mono and bis amides, conformationally locked calixarenes, ref. 6), and linear (hydroxamic tertiary amines) structures, and isoform-selective, and of triazole-based ligands of microsomal prostaglandin E2 synthase (mPGES-1, see ref. 12 and 14), and heat shock protein 90 (see ref. 27-28, 34-38 and 42-43). For each of this described studied, the good qualitative accordance between the calculated and experimental data has made possible the identifications of new lead compounds, rationalizing in this way, the key features to the target inhibition.
b) Rationalization of the biological activity of compounds by the study of the drug-receptor interactions. Molecular docking was used for the detailed study of anti-inflammatory and antitumoral compounds whose activities are known a priori. In fact, thanks to this procedure, in this thesis several rationalizations of binding modes were reported related to Ugi products derivatives of CHAP 1 (HDAC inhibitors, see ref. 4), new and potent inhibitor of NMPRTAse analogs of FK866 and CHS 828 (NMPRTase, see ref. 7), marine natural products as inhibitors of hsPLA2 (e.g., see ref. 13, 19), 4-methylen sterols extracted from Theonella swinhoei as ligands of FXR and PXR (see ref. 11, 17, 20-22), and known compounds as taurolitholic acid and ciprofloxacin, agonists of TGR5 (see ref. 24). Through the in silico methodology the putative binding modes for the reported molecules was described offering a complete rationalization of docking results, evaluating the influence of the ligand-target interactions (e.g., hydrophobic, hydrophilic, electrostatic contacts) on the biological activity.
c) Determination of relative configuration and fingerprint of natural products
The complete comprehension of the three-dimensional structure of synthetic or isolated molecules is fundamental to design and characterize new platform potentially utilizable in therapy. On this basis, the combined approach between the quantum mechanical (QM) calculation of NMR parameters and NMR spectroscopy (see ref. 8 and 30) was revealed a very useful mean to lead the total synthesis of natural product toward the right isomer reducing the amount time and resources (see ref. 15). Moreover, the stereostructure assignment of marine natural products conicasterol F and its analog thonellasterol by a novel combined approach between the quantitative interproton distance determinations by ROE and quantum mechanical calculations of chemical shifts (see ref. 10). More recently, she was involved in a new project where the NMR spectroscopy of natural compound, namely cocaine, has supported a Police investigation on a cocaine distribution network (see ref. 26). In particular, 1H NMR spectral analysis in conjunction with multivariate analysis was used to identify the chemical ‘‘fingerprint’’ of cocaine samples, and to link cocaine samples based on this information.
In summary, during these twelve years of research experience in NMR techniques, Molecular Dynamics of synthetic/natural products, Molecular Docking, Ab Initio Quantum Mechanical Calculation, Ph.D. Maria Giovanna Chini was the author of 43 scientific papers, 1 chapter of the book, and up to 15 communications to national and international meetings.