From plant flavonoids to drug candidate: Solubility enhancement of Kaempferol

We developed novel kaempferol prodrugs by conjugating all or selected hydroxyl groups of naturally derived kaempferol with carbamate ester–derived promoieties via an N-monosubstituted carbamate ester linkage to enhance water solubility. The synthesized derivatives significantly improved the aqueous solubility than native kaempferol. The increased solubility and bioavailability has increased biological and therapeutic efficacy of naturally derived kaempferol due to improved absorption, systemic availability and interaction with biological targets. These findings highlight the N-monosubstituted carbamate ester moiety as versatile prodrug design strategy for plant polyphenols and suggested a promising approach to improve the pharmacological action of natural kaempferol in plant-based therapeutic development.