Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: Identification of a lead for anti-inflammatory drug

Synthesis of Chromone-Related Pyrazole Compounds

“…( E )-3-[(2-Pyrazolin-/pyrazolidin-4-ylidene)methyl]chromones can be obtained in a very straightforward way through Knoevenagel condensation of 3-formylchromones with appropriate pyrazolin-5-ones [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] and pyrazolidine-3,5-diones [ 47 ], respectively. The 3-formylchromones have three active sites; the chromone carbonyl group, carbon 2 and the formyl group.…”

“…The authors observed that the reactions were very clean and afforded compounds 53 in high yields when using ultrasounds (72–89%) (step (v), Scheme 14 ) or microwave irradiation (68–81%) (step (vi), Scheme 14 ) requiring short time for completion (2–10 min) whereas in conventional heating method the reaction time was 20–25 min and the yields were comparatively poor (56–74%) (step (iv), Scheme 14 ) [ 40 ]. The same type of reaction involving other 3-formylchromones and 3-substituted-1-aryl-2-pyrazolin-5-ones in acetic acid under ultrasound or microwave irradiation in solvent-free conditions afforded also the corresponding ( E )-3-[(1-aryl-3-methyl-5-oxo-2-pyrazolin-4-ylidene)methyl]chromones 53 (steps (v) and (vi), Scheme 14 ) [ 42 , 43 , 44 , 45 , 46 ]. Some of these chromone-pyrazole conjugates 53 were screened for their biological potential.…”

“…Thus, compound 53 (R 1 = R 2 = R 3 = R 4 = H, R 5 = Me, Ar = 3-ClC 6 H 4 ) exhibited mild growth inhibitory activity (30–40%) in four human tumor cell lines (RPMI-8226, SR, M14 and UO-31) [ 43 ]. On the other hand, compound 53 (R 1 = NO 2 , R 2 = R 4 = H, R 3 = F, R 5 = Me, Ar = 3-ClC 6 H 4 ) was revealed as a leading anti-inflammatory drug, presenting IC 50 values of 10 μM for both cyclooxygenase-1 and cyclooxygenase-2 enzymes [ 44 ]. Among the nine derivatives of 53 (R 5 = CF 3 or propyl, Ar = 2,3,5,6-F 4 C 6 H), some of them showed promising antibacterial activity against Staphylococcus aureus , Streptococcus pyogenes , Escherichia coli and Pseudomonas aeruginosa and fungal pathogen Candida albicans , being none of them active for Aspergillus niger and Aspergillus clavatus fungal strains [ 45 ].…”

Chromones: A Promising Ring System for New Anti‐inflammatory Drugs

“…Following this idea, several hybrids containing chromone and indole groups were synthesized, and their COX inhibitory activities were evaluated (Figure ) . Relative to chromone‐ and indole‐based drugs, the combination of chromone and oxindole (e.g., compounds 7 ; Figure ) resulted in considerable inhibitory activity and selectivity for COX‐2 over COX‐1.…”

“…This study by Shaveta et al. has proven that hybrids, obtained by combining two bioactive groups, exhibit significantly higher biological activity than their individual components . In a subsequent study by Shaveta and co‐workers, the biologically significant group chrysin was combined with indole and pyrazole rings.…”