Profile

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

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:

1. 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.
2. 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.
3. 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.
4. 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).
5. 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.
6. 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.
7. 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.

Development of novel tools for dissection of central versus peripheral dopamine D2-like receptor signaling in dysglycemia.

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)

Linkers in Bitopic Agonists Shape Bias Profile among Transducers for the Dopamine D2 and D3 Receptors

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)

Structure of the dopamine D3 receptor bound to a bitopic agonist reveals a new specificity site in an expanded allosteric pocket.

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)

Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D₃ (D₃R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics.

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)

Chiral Cyclic Aliphatic Linkers as Building Blocks for Selective Dopamine D₂ or D₃R Receptor Agonists.

Battiti FO, Zaidi SA, Katritch V, Newman AH, Bonifazi A.

J Med Chem. doi: 10.1021/acs.jmedchem.1c01433. PMID: 34699207 (2021)

Scaffold Hybridization Strategy Leads to the Discovery of Dopamine D₃Receptor-Selective or Multitarget Bitopic Ligands Potentially Useful for Central Nervous System Disorders.

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)

Novel Dual-Target μ-Opioid Receptor and Dopamine D₃ Receptor Ligands as Potential Nonaddictive Pharmacotherapeutics for Pain Management.

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)

The Significance of Chirality in Drug Design and Synthesis of Bitopic Ligands as D₃ Receptor (D₃R) Selective Agonists.

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

Advances in drug design and therapeutic potential of selective or multitarget 5-HT1A receptor ligands.

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)

Targeting orexin receptors: Recent advances in the development of subtype selective or dual ligands for the treatment of neuropsychiatric disorders.

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)

The neuromedin U system: Pharmacological implications for the treatment of obesity and binge eating behavior.

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)

2016 Philip S. Portoghese Medicinal Chemistry Lectureship: Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts.

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/