Synthesis of amide-spacered dimers of ursolic and oleanolic acid

Abstract

<jats:p>Transdermal therapeutic systems can release drug substances slowly and in a controlled manner from a drug depot. To provide a slow-release form of ursolic and oleanolic acid amide-spacered dimers were synthesized from the parent acids and diamines of variable chain lengths. These dimers were assayed in sulforhodamine B (SRB) assays for their cytotoxicity since as a pre-requisite for their use in slow-release forms these substances must not exert any unfavorable side-effects such as cytotoxicity. As a result of long term incubation up to 96 hours, none of these compounds showed any significant cytotoxicity in sulforhodamine B assays.</jats:p>

Recent Advances in the Use of the Dimerization Strategy as a Means to Increase the Biological Potential of Natural or Synthetic Molecules

“…Another interesting example is the pyrrolo[2,1−c][1,4]benzodiazepine dimers 52 and 53 , which displayed cytotoxic activity in the picomolar range for all cancer cell lines tested [ 41 ]. Nevertheless, in some cases, dimerization leads to poor activity, such as for the unsaturated bis-norcantharimides dimers 38 and 39 [ 29 ] and for the ursolic and oleanolic acid dimers 80b and 81b [ 69 ]. The main cause for low biological activity is generally due to low solubility and bioavailability of the resulting compounds; hence, dimers of highly soluble drugs should be first considered as strong candidates for the likely outcome of potent new medicine.…”

“…Terpenoids are an important class of natural products with diverse biological properties (e.g., anti-inflammatory, antioxidant, and anticancer) and are often used in traditional herbal medicine. Several dimers of ursolic and oleanolic acid ( 78a and 79a ) were recently reported by Hoenke et al [ 69 ]. They were formed with the goal of improving their anticancer potential.…”