Acronycine-Type Alkaloids : Chemistry and Biology

New Synthetic Routes to Acronycine, Noracronycine, and Their Analogues

“…6 Among these alkaloids, acronycine (1) is isolated from the bark of Acronychia baueri 7 and exhibits strong antitumor and antiproliferative activities on several tumor models, including leukemia, sarcoma, myeloma, carcinoma, and melanoma. [8][9] Noracronycine (2) was isolated from Medicosma subsessilis (Figure 1). 10 Various analogues have been synthesized and studied, and their structure-activity relationships have shown that the pyranyl ring is essential for the cytotoxic and antitumor properties.…”

Rutaceous alkaloids as models for the design of novel antitumor drugs

“…Despite this promising antitumor activity, the mechanism of action of acronycine at both cellular and molecular levels has not been yet clearly established. In this context, none of the structural analogues prepared the first 25 years following the description of the biological properties of acronycine presented a better profile than the parent compound (Gerzon and Svoboda 1983;Tillequin et al 1998). Nevertheless, these results permitted to delineate structural features indispensable to observe the pharmacological activity.…”

Antitumour acridines

“…Acronycine (compound 20, Figure 3) belongs to the large family of natural acridone alkaloids [13]. Acronycine was shown to be cytotoxic against a large range of tumour cells in vitro and displays significant antitumour activities in vivo.…”

“…Acronycine was shown to be cytotoxic against a large range of tumour cells in vitro and displays significant antitumour activities in vivo. However, Phase I/II clinical evaluation in patients with refractory multiple myeloma only produced a partial response, related to moderate potency and low water solubility of the drug [13]. Structure-activity relationships (SARs) among acronycine derivatives clearly established the importance of the 1,2-double bond located in the dimethylchromene ring.…”