Synthesis, molecular properties, anti-inflammatory and anticancer activities of novel 3-hydroxyflavone derivatives

Mansour Znati; Claire Bordes; Valérian Forquet; Pierre Lantéri; Hichem Ben Jannet; Jalloul Bouajila

doi:10.1016/j.bioorg.2019.103009

Synthesis, molecular properties, anti-inflammatory and anticancer activities of novel 3-hydroxyflavone derivatives

Bioorg Chem. 2019 Aug:89:103009. doi: 10.1016/j.bioorg.2019.103009. Epub 2019 May 22.

Authors

Mansour Znati¹, Claire Bordes², Valérian Forquet², Pierre Lantéri², Hichem Ben Jannet³, Jalloul Bouajila⁴

Affiliations

¹ Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity (LR11ES39), Team: Medicinal Chemistry and Natural Products, Faculty of Science of Monastir, University of Monastir, Avenue of Environment, 5019 Monastir, Tunisia; University of Toulouse, Paul-Sabatier University, Faculty of Pharmacy Toulouse, Laboratory of IMRCP UMR CNRS 5623, 118 route de Narbonne, F-31062 Toulouse, France.
² Univ Lyon, Université Claude Bernard Lyon 1, CNRS, ISA (Institut des Sciences Analytiques), UMR CNRS n°5280, 5 rue de la Doua, F-69100 Villeurbanne, France.
³ Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity (LR11ES39), Team: Medicinal Chemistry and Natural Products, Faculty of Science of Monastir, University of Monastir, Avenue of Environment, 5019 Monastir, Tunisia. Electronic address: hichem.bjannet@gmail.com.
⁴ University of Toulouse, Paul-Sabatier University, Faculty of Pharmacy Toulouse, Laboratory of IMRCP UMR CNRS 5623, 118 route de Narbonne, F-31062 Toulouse, France. Electronic address: jalloul.bouajila@univ-tlse3.fr.

PMID: 31158579
DOI: 10.1016/j.bioorg.2019.103009

Abstract

A new series of 3-hydroxyflavones (1-46) were synthesized according to the Claisen-Schmidt followed by Algar-Flynn-Oyamada reactions (AFO) in one step. The synthesized flavonoids were characterized by ¹H NMR, ¹³C NMR and DCI-HRMS. All the synthesized compounds were tested in vitro for their 15-lipoxygenase inhibitory and cytotoxic activity against the human cell lines HCT-116 (Human colon carcinoma), IGROV-1 and OVCAR-3 (human ovarian carcinoma). It has been found that the derivatives 25, 37 and 45 were the most actives against HCT-116 (IC₅₀ = 8.0, 9.0 and 9.0 μM, respectively) and against IGROV-1 (IC₅₀ = 2.4, 5.0 and 6.0 μM, respectively). The derivatives 14 and 21 exhibited the higher anti-inflammatory activity at 100 μM with PI values of 76.50 and 72.70%, respectively. Molecule description was performed with DFT calculations, the drug likeness and bioactivity scores. The results exhibted that some compounds are in linear correlation with Lipinski's rule of five showing good drug likeness and bioactivity score for drug targets.

Keywords: 15-lipoxygenase inhibitory; 3-hydroxyflavones; Cytotoxic activity; DFT calculations; Drug likeness; Molecular propreties.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Arachidonate 15-Lipoxygenase / metabolism*
Cell Line, Tumor
Cell Proliferation / drug effects
Density Functional Theory
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Flavonoids / chemical synthesis
Flavonoids / chemistry
Flavonoids / pharmacology*
HCT116 Cells
Humans
Lipoxygenase Inhibitors / chemical synthesis
Lipoxygenase Inhibitors / chemistry
Lipoxygenase Inhibitors / pharmacology*
Molecular Structure
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Flavonoids
Lipoxygenase Inhibitors
Arachidonate 15-Lipoxygenase
3-hydroxyflavone