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<p>The current work initially focused on the custom synthesis of ILB-162, an innovative calcineurin inhibitor, known chemically as N-(5-chloro-2-hydroxyphenyl)-2-(morpholin-4-yl-methyl) benzamide to get a yield of 25&#xa0;mg with 90.73% purity and confirmed its significant calcineurin inhibitory potential in vitro having very low IC<sub>50</sub> value (0.057&#xa0;µM). Further assessment in L929 cells revealed low cytotoxicity (LD<sub>50</sub> = 305.28&#xa0;µg/mL) and the neuroprotection evaluated in SHSY 5Y cells induced with 6OHDA, identified 50&#xa0;µg/mL as the optimal protective dose. The Parkinson’s disease (PD) models in the current study were divided into three groups; Normal control (NC) without any treatment, Disease Control (DC) induced with chemical screens (6OHDA for SHSY 5Y cell line and Rotenone for <i>C. elegans</i>) and treated with ILB-162 group (induced cells treated with 50&#xa0;µg/mL ILB-162), for accessing molecular as well as behavioral effects. In the Cell line models, ILB-162 treatment significantly reduced intracellular ROS as well as reversed α-synuclein overexpression, indicating its potential to reverse the molecular pathology underlying PD. Subsequent studies using <i>C. elegans</i> PD model assessed toxicity (LD<sub>50</sub> = 1436.39&#xa0;µM) comparable to in vitro observations and demonstrated the outstanding capability of ILB-162 to restore the dopamine-dependent behaviors which were disrupted in DC. These findings suggest that ILB-162 can be a promising therapeutic candidate against PD, justifying the further development.</p>

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Neuroprotective propensity of N-(5-chloro-2-hydroxyphenyl)-2-(morpholin-4-yl-methyl) benzamide, an inventive calcineurin inhibitor, in biological models of Parkinson’s disease

  • 期刊论文

  • 发表日期：

    2025年5月2日

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  • R. M. Nivya,
  • Amitha Joy

摘要

The current work initially focused on the custom synthesis of ILB-162, an innovative calcineurin inhibitor, known chemically as N-(5-chloro-2-hydroxyphenyl)-2-(morpholin-4-yl-methyl) benzamide to get a yield of 25 mg with 90.73% purity and confirmed its significant calcineurin inhibitory potential in vitro having very low IC50 value (0.057 µM). Further assessment in L929 cells revealed low cytotoxicity (LD50 = 305.28 µg/mL) and the neuroprotection evaluated in SHSY 5Y cells induced with 6OHDA, identified 50 µg/mL as the optimal protective dose. The Parkinson’s disease (PD) models in the current study were divided into three groups; Normal control (NC) without any treatment, Disease Control (DC) induced with chemical screens (6OHDA for SHSY 5Y cell line and Rotenone for C. elegans) and treated with ILB-162 group (induced cells treated with 50 µg/mL ILB-162), for accessing molecular as well as behavioral effects. In the Cell line models, ILB-162 treatment significantly reduced intracellular ROS as well as reversed α-synuclein overexpression, indicating its potential to reverse the molecular pathology underlying PD. Subsequent studies using C. elegans PD model assessed toxicity (LD50 = 1436.39 µM) comparable to in vitro observations and demonstrated the outstanding capability of ILB-162 to restore the dopamine-dependent behaviors which were disrupted in DC. These findings suggest that ILB-162 can be a promising therapeutic candidate against PD, justifying the further development.