Synthetic studies and biological evaluation of chromone - 3 - carbaldehydes

Abstract

Chromones are well known naturally occurring heterocyclic compounds with oxygen as a heteroatom. Chromones are also one of the major classes of naturally occurring compounds, and the interest in their chemistry is due to their wide range of their biological activity. In this study, three classes of target compounds were synthesized through three different pathways. The first pathway, chromone-3-carbaldehyde analogues were afforded in good to excellent yield followed by the oxidation thereof to 4-oxo-4H-chromene-3-carboxylic acids. A series of chromone-3-carboxamides was obtained from corresponding 4-oxo-4H-chromene-3-carboxylic acid via the in situ generation of the corresponding acid chloride in good yield. The second class of compounds were achieved by reacting corresponding chromone-3-carbaldehyde analogues with thiazolidine-2,4-dione to afford 5-((4-oxo-4H-chromen-3-yl)methylene)thiazolidine-2,4-dione analogues. The third class of compounds followed the same reaction pathway as the second class of compounds from corresponding 8-allyl-chromone-3-carbaldehyde analogues to afford 5-((8-allyl-4-oxo-4H-chromen-3-yl)methylene)thiazolidine-2,4-dione analogues in good yield. Compounds were characterized by 1D NMR (1H, 13C and DEPT), 2D NMR (COSY, HSQC and HMBC), IR and elemental analysis (CHN analysis). Selected synthesized chromone derivatives were evaluated in vitro for two biological assays; namely trypanocidal activity and cytotoxicity. Among all tested compounds, 41A, 55B and 63D displayed promising trypanocidal activity by reducing the percentage parasite viability to 0.61, 0.15 and 0.21 respectively. These results were further substantiated by their IC50 values 4.3, 1.3 and 1.9 μg/mL respectively. Compounds 41B and 59A also showed significant trypanocidal activity, however it was below the positive control. Compounds 41A and 55B displayed cytotoxicity against the HeLa cells whilst compound 63D displayed no toxicity against the HeLa cells.