Synthesis and Sar Study of Diarylpentanoid Analogues as New Anti-Inflammatory Agents

Abstract

A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma , which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta-and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives.

1H‐NMR metabolomics for evaluating the protective effect of Clinacanthus nutans (Burm. f) Lindau water extract against nitric oxide production in LPS‐IFN‐γ activated RAW 264.7 macrophages

“…The NO inhibition assay was performed as previously reported by Leong et al, with slight modification. Each sample was prepared at a concentration of 1000 μg/mL in well.…”

“…The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) cell viability assay was conducted according to the method optimised by Leong et al . with slight modification.…”

“…The NO inhibition assay was performed as previously reported by Leong et al, 18 The results were expressed as IC 50 (the half maximal inhibitory concentration).…”

Nitric oxide inhibitory activity and antioxidant evaluations of 2-benzoyl-6-benzylidenecyclohexanone analogs, a novel series of curcuminoid and diarylpentanoid derivatives

“…[19][20][21][22][23] Unlike curcumin, diarylpentanoids are chemically stable at physiological pH and metabolically stable in rat liver microsomes, which make them the most impactful candidates among curcuminoids deserving further intensive investigations towards developing novel bioactive molecules with good stability and bioavailability Previously, we have shown that α,β-unsaturated β-diketone and cyclohexanone fragments are crucial for diarylpentanoids' bioactivities in different studies. 15,26 In continuing our effort on the search of new anti-inflammatory agent, we have now synthesized a series of 2-benzoyl-6-benzylidenecyclohexanone analogues, a novel family of diarylpentanoid which incorporated the integration of α,β-unsaturated β-diketone and cyclohexanone moieties. As represented in Scheme 1, compounds 1-24 (III) were successfully synthesized through a series of reactions, which involved benzoylation of cyclohexanone and aldol condensation with aryl aldehydes.…”

Synthesis and in vitro Bioactivity Evaluation of New Galactose and Fructose Ester Derivatives of 5‐Aminosalicylic Acid

“…[34] [35] In this work, the NO inhibition activity of 6 and 7 was evaluated in IFN-c/LPS-stimulated RAW264.7 macrophages and compared with the initial drug. It responds to these threats by secreting proinflammatory mediators.…”