Scholarlink

Abstract <p>Chronic inflammation drives various non-communicable diseases, necessitating the search for novel therapeutic agents. Integrating heteroatoms in the inhibitor drug design enhances potency by enabling multifaceted interactions with the target cell receptor. Herein, a new series of orthocetamol azo derivatives, featuring a nitrogen-based moiety (–N=N–), was synthesized via the diazotization of orthocetamol with substituted aniline derivatives, yielded 31–95%. The <i>in vitro</i> anti-inflammatory evaluation on orthocetamol azo derivatives showed a minimum 49.4±1.3% NO inhibition against LPS-induced RAW 264.7 macrophages at 50 μM. Notably, <i>para</i>-bromo substituted compound exhibited the most potent NO inhibition of 92.8±0.3%, with an IC<sub>50</sub> value of 16.0±0.6 µM, comparable to the positive control, Dexamethasone (16.9±2.2 µM). <i>In silico</i> molecular docking analysis of the <i>p</i>-Br orthocetamol azo against the COX-2 enzyme (PDB ID: 5IKR), a key regulator often associated with NO production pathways, revealed a binding affinity of –7.2 kcal/mol driven by a stable hydrogen bond with TYR355 and a predicted isoform-selective π-alkyl interaction with VAL523. While these computational insights suggest a potential preference for COX-2, further pharmacokinetic profiles of <i>p</i>-Br orthocetamol azo confirmed its druglikeness through adherence to the Lipinski rule, in addition to an optimal balance of ADMET properties. The finding suggested <i>p</i>-Br orthocetamol azo could serve as a promising therapeutic candidate, warranting further <i>in vitro</i> enzymatic assays to experimentally validate its COX-1/COX-2 selectivity profile in anti-inflammatory drug development.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Synthesis, In Vitro, and In Silico Anti-Inflammatory Screening of Orthocetamol Azo Derivatives

  • 期刊论文

  • 发表日期：

    2026年7月30日

查看全文
  • Nur Alia Syahilda Zikri,
  • Sharon Leong Hui Jiun,
  • Filicia Fiona Gaba Ferry,
  • Nor Hisam Zamakshshari,
  • Ainaa Nadiah Abd Halim,
  • Mah Siau Hui,
  • James Yew Zhi Jun,
  • Hanan Ibrahim Mohamed Yassin Yunis,
  • Noraizan Aggie,
  • Yeo Kai Wei,
  • Davlye Noissy Diosing

摘要

Abstract

Chronic inflammation drives various non-communicable diseases, necessitating the search for novel therapeutic agents. Integrating heteroatoms in the inhibitor drug design enhances potency by enabling multifaceted interactions with the target cell receptor. Herein, a new series of orthocetamol azo derivatives, featuring a nitrogen-based moiety (–N=N–), was synthesized via the diazotization of orthocetamol with substituted aniline derivatives, yielded 31–95%. The in vitro anti-inflammatory evaluation on orthocetamol azo derivatives showed a minimum 49.4±1.3% NO inhibition against LPS-induced RAW 264.7 macrophages at 50 μM. Notably, para-bromo substituted compound exhibited the most potent NO inhibition of 92.8±0.3%, with an IC50 value of 16.0±0.6 µM, comparable to the positive control, Dexamethasone (16.9±2.2 µM). In silico molecular docking analysis of the p-Br orthocetamol azo against the COX-2 enzyme (PDB ID: 5IKR), a key regulator often associated with NO production pathways, revealed a binding affinity of –7.2 kcal/mol driven by a stable hydrogen bond with TYR355 and a predicted isoform-selective π-alkyl interaction with VAL523. While these computational insights suggest a potential preference for COX-2, further pharmacokinetic profiles of p-Br orthocetamol azo confirmed its druglikeness through adherence to the Lipinski rule, in addition to an optimal balance of ADMET properties. The finding suggested p-Br orthocetamol azo could serve as a promising therapeutic candidate, warranting further in vitro enzymatic assays to experimentally validate its COX-1/COX-2 selectivity profile in anti-inflammatory drug development.