2. Academic Validation
  3. Chemotherapeutics for Toxoplasma gondii: Molecular Biotargets, Binding Modes, and Structure-Activity Relationship Investigations

Chemotherapeutics for Toxoplasma gondii: Molecular Biotargets, Binding Modes, and Structure-Activity Relationship Investigations

  • J Med Chem. 2021 Dec 23;64(24):17627-17655. doi: 10.1021/acs.jmedchem.1c01569.
Rong-Zhen Wu 1,  Huai-Yu Zhou 2,  Jing-Feng Song 3,  Qiao-Hong Xia 2,  Wei Hu 4,  Xiao-Dong Mou 1,  Xun Li 1 5
Affiliations

Affiliations

  • 1 Institute of Materia Medica, Shandong First Medical University and Shandong Academy of Medical Sciences, no. 6699 Qingdao Road, Ji'nan, Shandong 250117, PR China.
  • 2 Department of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, no. 44 Wenhua Xi Road, Ji'nan, Shandong 250012, PR China.
  • 3 School of Pharmaceutical Sciences and Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, no. 1168 Chunrong Xi Road, Kunming, Yunnan 650500, PR China.
  • 4 State Key Laboratory of Microbial Technology, School of Life Science, Shandong University, no. 72 Binhai Road of JiMo, Qingdao, Shandong 266237, PR China.
  • 5 Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing 100192, PR China.
PMID: 34894691 DOI: 10.1021/acs.jmedchem.1c01569
Abstract

Toxoplasmosis, an infectious zoonotic disease caused by the apicomplexan Parasite Toxoplasma gondii (T. gondii), is a major worldwide health problem. However, there are currently no effective options (chemotherapeutic drugs or prophylactic vaccines) for treating chronic latent toxoplasmosis Infection. Accordingly, seeking more effective and safer chemotherapeutics for combating this disease remains a long-term and challenging objective. In this paper, we summarize possible molecular biotargets, with an emphasis on those that are druggable and promising, including, without limitation, calcium-dependent protein kinase 1, bifunctional thymidylate synthase-dihydrofolate reductase, and farnesyl diphosphate synthase. Meanwhile, as important components of medicinal chemistry, the binding modes and structure-activity relationship profiles of the corresponding inhibitors were also illuminated. We anticipate that this information will be helpful for further identification of more effective chemotherapeutic interventions to prevent and treat zoonotic infections caused by T. gondii.

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