Synthesis of 3-substituted-4-hydroxycoumarins and their biological activities

Abstract

Two types of 3-substituted-4-hydroxycoumarins: dicoumarols and 3-alkyl-4-hydroxycoumarins were synthesized. Fifty dicoumarols and analogues were derived from the condensation reaction between 4-hydroxycoumarins and interesting aldehydes. Fifteen 3-alkyl-4-hydroxycoumarins were synthesized by reductive fragmentation of dicoumarols using sodium cyanoborohydride. These well-characterized compounds were subjected to three bioassays. For brine shrimp lethality test, high activities were observed in four dicoumarols, namely, [3,3’-(4-n-hexyloxy-3-methoxy benzylidene)]bis-, [3,3’-((E)-3-phenylprop-2-enylidene)] bis-, [3,3’,3”,3”-(1,5-pentylidene)] tetrakis and [3-(l-hydroxy-2-trichloroethylidene)]-4-hydroxycoumarin and in general 3-alkyl-4-hydroxycoumarins were found to dispply higher activity than dicoumarols. In the case of antibacterial activity, these compounds selectively inhibited inhibited against four bacteria including Listeria monoctogenes, Bacillus cereus, Staphylococus aureus and flat sour spoilage, 3-Allkyl-4-hydroxycoumarins revealed higher activity than dicoumarols and displayed the activity comparable with two antibiotic drugs. For antiviral activity against HsV-1 and HSV-2 virus, it was found that that the activity of dicoumarols against HSV-1 was higher than HSV-2 but vice versa for 3-alky-4-hydroxycoumarins. Dicoumarols with 2-nitro and 4-trifluoromethyl substituents on benzylidene ring and a 3-methoxy group on a benzylidene ring of fused ring of fused ring displayed 100% inhibition against HSV-1.