In Vitro Anti‐Toxoplasma gondii Activity Evaluation of a New Series of Quinazolin‐4(3H)‐one Derivatives

Toxoplasmosis post serious threaten to human health, leading to severely eye and brain disease, especially for immunocompromised patients and pregnant women. The multiple side effects and long dosing period of current main treatment regiments calls for high effective and low toxicity anti‐toxoplasmo...

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Bibliographic Details
Published in:Chemistry & biodiversity 2021-12, Vol.18 (12), p.e2100687-n/a
Main Authors: Deng, Yu, Mu, Hao, Li, Hong‐Bo, Fu, Li‐Zhi, Tang, Da, Wu, Tao, Huang, Shu‐Heng, Li, Cheng‐Hong
Format: Article
Language:English
Subjects:
antiproliferative agents
Antiprotozoal Agents - chemical synthesis
Antiprotozoal Agents - chemistry
Antiprotozoal Agents - pharmacology
Chains
cytotoxicity
Diaryl ethers
Dose-Response Relationship, Drug
Hydrophobicity
Immunocompromised hosts
in vitro
Molecular docking
Molecular Docking Simulation
Molecular Structure
Parasitic Sensitivity Tests
Phenotypes
Piperazine
Protozoa
Quinazolinones - chemical synthesis
Quinazolinones - chemistry
Quinazolinones - pharmacology
Side effects
Structure-activity relationship
Tachyzoites
Toxicity
Toxoplasma - drug effects
Toxoplasma gondii
Toxoplasmosis
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Summary:Toxoplasmosis post serious threaten to human health, leading to severely eye and brain disease, especially for immunocompromised patients and pregnant women. The multiple side effects and long dosing period of current main treatment regiments calls for high effective and low toxicity anti‐toxoplasmosis drugs. Herein, we report our efforts to synthesize a series of 2‐(piperazin‐1‐yl)quinazolin‐4(3H)‐one derivatives and investigate their activity against Toxoplasma gondii tachyzoites in vitro based on cell phenotype screening. Among the 26 compounds, 8w and 8x with diaryl ether moiety at the side chain of piperazine exhibited good efficacy to inhibit T. gondii, with IC50 values of 4 μM and 3 μM, respectively. Structure‐activity relationship (SAR) studies implies that hydrophobic aryl at the side chain would be preferred for improvement of activity. Molecular docking study reveals these two compounds appeared high affinity to TgCDPK1 by interaction with the hydrophobic pocket of ATP‐binding cleft.
ISSN:1612-1872
1612-1880
DOI:10.1002/cbdv.202100687