Synthesis and evaluation of chromone-2-carboxamide derivatives as cytotoxic agents and 5-lipoxygenase inhibitors

Fatima Bousejra-El Garah (1) , Barbora Lajoie Halova (1) , Jean-Pierre Souchard (2) , Geneviève Baziard (1) , Jalloul Bouajila (2) , Salomé El Hage (1)

1 LGC - Laboratoire de Génie Chimique
2 IMRCP - Interactions moléculaires et réactivité chimique et photochimique

In the present study, we prepared a series of 21 chromone carboxamide derivatives bearing diverse amide side chains. Their potency to inhibit the proliferation of breast (MCF-7), ovarian (OVCAR and IGROV), and colon (HCT-116) cancer cell lines, was evaluated in vitro using the MTT assay. Among these compounds, 13 showed promising cytotoxic activity against at least one cancer cell line with IC50 in the range 0.9–10 μM. Our compounds were also screened for their anti-inflammatory activity as putative inhibitors of 5-lipoxygenase. Structure-activity relationships studies on our chromone carboxamide derivatives revealed that the presence of a 6-fluoro substituent on the chromone nucleus (R1) or propyl and 3-ethylphenyl groups on the amide side chain (R2) has a positive impact on the cytotoxic activity. In terms of the anti-inflammatory activity, hydrophilic chromone carboxamide derivatives showed greater 5-lipoxygenase inhibition. The physico-chemical properties of chromone carboxamides are in accordance with the general requirements of drug development process and ligand efficiency values allow further structure optimization, with compound 4b as a lead.

Mots clés: Chromone carboxamides; Cytotoxic activity; Anti-inflammatory effect; Lipophilicity; SAR

Domaines: Génie chimique; Génie des procédés

Fatima Bousejra-El Garah, Barbora Lajoie Halova, Jean-Pierre Souchard, Geneviève Baziard, Jalloul Bouajila, et al.. Synthesis and evaluation of chromone-2-carboxamide derivatives as cytotoxic agents and 5-lipoxygenase inhibitors. Medicinal Chemistry Research, 2016, 25 (11), pp.2547-2556. ⟨10.1007/s00044-016-1691-y⟩. ⟨hal-01882586⟩