2. Academic Validation
  3. Design and characterization of N-oxide cinnamanilide derivative PX5-9: Improved solubility and BDNF upregulation

Design and characterization of N-oxide cinnamanilide derivative PX5-9: Improved solubility and BDNF upregulation

  • Bioorg Med Chem Lett. 2025 Sep 1:125-126:130266. doi: 10.1016/j.bmcl.2025.130266.
Zhixian Zhang 1,  Qianhui Shen 2,  Yanping Chen 1,  Zhi Liang 1,  Yuan Liu 1,  Yu Ren 1,  Cailv Wei 1,  Kang Jia 2,  Chao Ding 1,  Shisong Wang 1,  Rongbiao Pi 3
Affiliations

Affiliations

  • 1 School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, P.R. China.
  • 2 School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, P.R. China.
  • 3 School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, P.R. China; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, P.R. China. Electronic address: pirb@mail.sysu.edu.cn.
PMID: 40412448 DOI: 10.1016/j.bmcl.2025.130266
Abstract

Compound 5, a cinnamanilide derivative, upregulates brain derivated neurotrophic factor (BDNF) expression but with low soluablity. In this study, PX5-9, a N-oxide derivative of 5, demonstrated significant protective effects in the HT22 glutamate-induced toxicity model and showed no significant toxicity at 30 μM. Western blot analysis confirmed that PX5-9 increased BDNF levels similar to 5. Solubility tests revealed a significant improvement in PX5-9 (37.10 ± 0.33 μg/mL) compared to 5 (< 15 ng/mL). Pharmacokinetic studies of PX5-9 revealed favorable properties, fast absorption and also can be transformated into parent compound 5, suggesting it is a potential candidate for these diseases involving with BDNF. The N-oxide modification might be a good prodrug design to enhance solubility while preserving biological activity.

Keywords

BDNF; Cinnamanilide; N-oxide; Pharmacokinetics; Solubility.

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