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Medicinal Chemistry and Drug Discovery
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Associate Professor
Medicinal Chemistry and Drug Discovery
+1 (409)-266-0735
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MS/PharmD, Pharmaceutical Chemistry and Technology, 2010, Università degli Studi di Camerino, Camerino (MC), Italy
PhD, Pharmaceutical Sciences, 2014, Università degli Studi di Camerino, Camerino (MC), Italy
Postdoctoral Fellow, 2014-2019, National Institute on Drug Abuse (NIH/NIDA-IRP), Baltimore (MD), USA
Research Fellow, 2019-2022, National Institute on Drug Abuse (NIH/NIDA-IRP), Baltimore (MD), USA
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Areas of Research
Medicinal Chemistry; Organic Synthesis; Chirality in Drug Design; Bitopic and Multi-Target Drug Design; Radioligand Binding Assays; Translational Drug Discovery; G protein-coupled receptors; Neuropsychiatric disorders and comorbidities; Poly-pharmacology.
Research Interests
Our primary research goals are directed toward the design, synthesis, and development of small molecules as pharmacological tools for neuroscience applications and potential therapeutics. Specifically, we primarily target G protein-coupled receptors (GPCRs). Our objectives include:
- Drug Discovery Campaigns: Our work in medicinal chemistry contributes to drug discovery campaigns, particularly in the fields of biased agonism/functional selectivity and poly-pharmacology.
- Ligand Development: We aim to create novel ligands that facilitate the understanding of cross-pharmacological modulation in receptors. Additionally, we investigate receptors’ pathway activations at the molecular level, elucidating their roles in the (patho)-physiology of the central nervous system (CNS) and peripheral tissues.
- Elucidating Ligand-Receptor Interactions: We strive in providing molecules to uncover ligand-receptor interactions, identify unique active and/or inactive receptor conformations, providing valuable insights into cellular processes. By studying specific GPCR-ligand complexes formation, signaling mechanisms and cellular functions using small molecules, we aim to provide the foundational insights necessary for safer therapeutic drug development.
- Advanced Techniques: We combine advanced organic chemistry methodologies, with an emphasis on chiral synthesis, and in vitro cell-/tissue-based radioligand binding assays. These techniques allow us to synthesize, characterize and screen new compounds to generate structure-activity relationships (SAR).
- Research Projects: Some of our ongoing projects involve the rational design of ligands targeting dopamine, opioid, and orexin receptors. We implement bitopic, bivalent, and multitarget drug design strategies.
- Therapeutic Applications: Our research has implications for treating locomotor disorders, high-impulsivity behaviors, pain, substance use disorders, sleep and feeding disorders, and comorbidities associated with neuropsychiatric conditions.
- Translational Potential: We continue to expand our multidisciplinary approach, collaborating nationally and internationally. Thanks to our collaborators, we integrate in silico models (docking and molecular simulation), pharmacokinetic, machine learning/artificial intelligence, molecular pharmacology and CryoEM to predict optimized ligand-target interactions and fine-tune the desired pharmacological profile of the new ligands. These efforts have the fundamental goal of advancing new lead candidates in in vivo pre-clinical models.
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Bonifazi A, Ellenberger M, Farino ZJ, Aslanoglou D, Rais R, Pereira S, Mantilla-Rivas JO, Boateng CA, Eshleman AJ, Janowsky A, Hahn MK, Schwartz GJ, Slusher BS, Newman AH, Freyberg Z.
Diabetes. doi: 10.2337/db24-0175. PMID: 38869519 (2024)
Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats.
Shen H, Ma Z, Hans E, Duan Y, Bi GH, Chae YC, Bonifazi A, Battiti FO, Newman AH, Xi ZX, Yang Y.
Neuropharmacology. doi: 10.1016/j.neuropharm.2024.110051. PMID: 38917939 (2024)
Semeano A, Garland R, Bonifazi A, Lee KH, Famiglietti J, Zhang W, JaeJo Y, Battiti FO, Shi L, Newman AH, Yano H
ACS Pharmacol Transl Sci. doi:10.1021/acsptsci.4c00119 (2024)
Arroyo-Urea S, Nazarova AL, Carrión-Antolí Á, Bonifazi A, Battiti FO, Lam JH, Newman AH, Katritch V, García-Nafría J.
Res Sq [Preprint]. doi: 10.21203/rs.3.rs-3433207/v1. PMID: 38196573 (2023)
Bonifazi A, Saab E, Sanchez J, Nazarova AL, Zaidi SA, Jahan K, Katritch V, Canals M, Lane JR, Newman AH.
J Med Chem. doi: 10.1021/acs.jmedchem.3c00417. PMID: 37467430 (2023)
Battiti FO, Zaidi SA, Katritch V, Newman AH, Bonifazi A.
J Med Chem. doi: 10.1021/acs.jmedchem.1c01433. PMID: 34699207 (2021)
Bonifazi A, Newman AH, Keck TM, Gervasoni S, Vistoli G, Del Bello F, Giorgioni G, Pavletić P, Quaglia W, Piergentili A.
ACS Chem Neurosci. doi: 10.1021/acschemneuro.1c00368. PMID: 34529404 (2021)
Bonifazi A, Battiti FO, Sanchez J, Zaidi SA, Bow E, Makarova M, Cao J, Shaik AB, Sulima A, Rice KC, Katritch V, Canals M, Lane JR, Newman AH.
J Med Chem. doi: 10.1021/acs.jmedchem.1c00611. PMID: 34011153 (2021)
Battiti FO, Cemaj SL, Guerrero AM, Shaik AB, Lam J, Rais R, Slusher BS, Deschamps JR, Imler GH, Newman AH, Bonifazi A.
J Med Chem. doi: 10.1021/acs.jmedchem.9b00702. PMID: 31257877 (2019)
Novel and Potent Dopamine D2 Receptor Go-Protein Biased Agonists.
Bonifazi A, Yano H, Guerrero AM, Kumar V, Hoffman AF, Lupica CR, Shi L, Newman AH.
ACS Pharmacol Transl Sci. doi: 10.1021/acsptsci.8b00060. PMID: 30775693 (2019)
Selected Review Articles
Giorgioni G, Bonifazi A, Botticelli L, Cifani C, Matteucci F, Micioni Di Bonaventura E, Micioni Di Bonaventura MV, Giannella M, Piergentili A, Piergentili A, Quaglia W, Del Bello F.
Med Res Rev. doi: 10.1002/med.22049. PMID: 38808959 (2024)
Bonifazi A, Del Bello F, Giorgioni G, Piergentili A, Saab E, Botticelli L, Cifani C, Micioni Di Bonaventura E, Micioni Di Bonaventura MV, Quaglia W.
Med Res Rev. doi: 10.1002/med.21959. PMID: 37036052 (2023)
Botticelli L, Micioni Di Bonaventura E, Del Bello F, Giorgioni G, Piergentili A, Quaglia W, Bonifazi A, Cifani C, Micioni Di Bonaventura MV.
Pharmacol Res. doi: 10.1016/j.phrs.2023.106875. PMID: 37517560 (2023)
Newman AH, Battiti FO, Bonifazi A.
J Med Chem. doi: 10.1021/acs.jmedchem.9b01105. PMID: 31499001 (2020)
Link to NCBI my bibliography:
https://www.ncbi.nlm.nih.gov/myncbi/1DqEc42q9m4wLX/bibliography/public/