Synthesis of Ursolic Acid Conjugates Containing a Furoxan Moiety

Abstract

Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) combined with NO donors (NO-NSAIDs) are attracting attention and are considered promising anti-cancer chemotherapy agents [1]. Compared with ordinary NSAIDs, NO-NSAIDs have low toxicity and fewer side effects, in particular, damage to the gastrointestinal tract and kidneys [2]. The use of NO donors in hybrids with NSAIDs can lead to synergism and increased anti-inflammatory activity [3]. Derivatives of 1,2,5-oxadiazole-2-oxide (furoxan) can be used as the NO donor. The synthesis of the conjugate of diclofenac and a furoxan derivative that exhibited high anti-inflammatory activity was reported [4]. Furoxan derivatives have been reported to have also antithrombotic [5], vasodilating [6], and bactericidal [7] activities. According to the literature, slightly toxic ursolic acid (UA) and several of its derivatives also had noticeable antiinflammatory activity [8]. Ursane-type compounds are being actively studied as potential anti-cancer chemotherapy agents. Conjugates of UA succinate and furoxan derivatives were prepared [9]. Several of the new compounds exhibited cytotoxic activity that exceeded those of UA and 5-fluorouracil. Herein, we communicate the preparation of new hybrids of UA and furoxan derivatives with the heterocycle occupying different positions on the terpene framework.