Pharmacochemical Study of Multitarget Amino Acids’ Hybrids: Design, Synthesis, In vitro, and In silico Studies
Medicinal chemistry (Shariqah (United Arab Emirates))(2024)
摘要
Introduction:Neuro-inflammation is a complex phenomenon resulting in several disorders.
ALOX-5, COX-2, pro-inflammatory enzymes, and amino acid neurotransmitters are tightly
correlated to neuro-inflammatory pathologies. Developing drugs that interfere with these targets
will offer treatment for various diseases.
Objective:Herein, we extend our previous research by synthesizing a series of multitarget hybrids
of cinnamic acids with amino acids recognized as neurotransmitters.
Methods:The synthesis was based on an in silico study of a library of cinnamic amide hybrids with
glycine, γ- aminobutyric, and L - glutamic acids. Drug-likeness and ADMET properties were subjected
to in silico analysis. Cinnamic acids were derived from the corresponding aldehydes by
Knoevenagel condensation. The synthesis of the amides followed a two-step reaction with 1-
hydroxybenzotriazole monohydrate and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride
in dry dichloromethane and the corresponding amino acid ester hydrochloride salt in the
presence of N,N,-diisopropyl-Nethylamine.
Results:The structure of the synthesized compounds was confirmed spectrophotometrically. The
new compounds, such as lipoxygenase, cyclooxygenase-2, lipid peroxidation inhibitors, and antiinflammatories,
were tested in vitro. The compounds exhibited LOX inhibition with IC50 values in
the low μM region).
Conclusion:Compounds 18a, 23b, and 11c are strong lipid peroxidation inhibitors (99%, 78%, and
92%). Compound 28c inhibits SLOX-1 with IC50 =8.5 μM whereas 11a and 22a highly inhibit
COX-2 (IC50 6 and 5 μM Hybrids 14c and 17c inhibit both enzymes. Compound 29c showed the
highest anti-inflammatory activity (75%). The in silico ADMET properties of 14c and 11a support
their drug-likeness.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要