AI Article Synopsis

  • The study focuses on new allylbenzenes designed as inhibitors for lipoxygenases, which play a role in reducing peroxidation activity by mimicking certain fatty acid structures.
  • Synthesis involved starting with 3-allyl-4-isopropoxybenzenamine and modifying it through chemical reactions to create final derivatives with varying potency against soybean 15-lipoxygenase (SLO).
  • Results indicated that the arrangement of allyl and amide groups significantly affects the inhibitors' potency, with certain compounds demonstrating stronger inhibition and improved binding energy.

Article Abstract

Objectives: Allylbenzenes have been recently developed as inhibitors of lipoxygenases. They decrease peroxidation activity via mimicking 1,4-unsaturated bonds of fatty acids by their allyl portion. We designed and synthesized new derivatives of allyl benzenes () with isopropoxy and amide substituents at ortho and meta positions towards allyl group, respectively. The inhibitory potency of the synthetized allylbenzenes against soybean 15-lipoxygenase (SLO) and subsequently structure-activity relationships was assessed.

Materials And Methods: 3-allyl-4-isopropoxybenzenamine () as starting material was synthesized by coupling of 4-nitropheol with allyl bromide, performing Claisen rearrangement and finally reduction of the nitro moiety. Final products were prepared via amidation of with the desired acyl chloride.

Results: Among the compounds, N-(3-allyl-4-isopropoxyphenyl)adamantan carboxamide () potentially showed best inhibition (IC = 1.35 µM) while with cyclopropyl carboxamide moiety was the weakest inhibitor and with phenyl carboxamide moiety showed no effect. Energy minimized 3D structures of the compounds were docked into the active site pocket of SLO. For the aliphatic amides, docking results showed compatibility between inhibitory potency and average Ki of the cluster conformers, in which their allyl moiety oriented towards SLO iron core. For the aliphatic analogs, by enlargement of the amide moiety size the inhibitory potency was increased.

Conclusion: Docking results showed that orientation of the amide and allyl moieties of the inhibitors in the active site pocket is the major factor in inhibitory potency variation. Based on the mentioned orientation, for cycloaliphatic amides, by enlargement of the amide moiety both inhibition potency and calculated binding energy increases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478253PMC
http://dx.doi.org/10.22038/ijbms.2020.36793.8763DOI Listing

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