Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents

Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives

“…In our diet, pentacyclic triterpenoids are considered relatively nontoxic to humans (Kuttan et al 2011). As we all known, ursolic acid (UA, compound 1) is the most predominant representative of pentacyclic triterpenoids and possesses considerable pharmacological activities, including: anti-HIV (Slamenov a et al 2006), anticancer (Rashid et al 2013), anti-inflammatory (Jung et al 2013), antidiabetic (Alqahtani et al 2013;Lee et al 2014;Wu et al 2014), and antibacterial activities . Importantly, it is also reported to have hepatoprotective activity (Liu 1995).…”

UP12, a novel ursolic acid derivative with potential for targeting multiple signaling pathways in hepatocellular carcinoma

“…Rashid et al [12] performed that UA-triazolyl derivatives displayed high level of antitumor activities compared with UA. Liu et al [13] found that incorporation of an acyl piperazine moiety at C-28 of UA while retaining the polar group at C-3 significantly improved the antitumor bioactivities of the compound.…”

1,2,3-Triazolyl esterization of PAK1-blocking propolis ingredients, artepillin C (ARC) and caffeic acid (CA), for boosting their anti-cancer/anti-PAK1 activities along with cell-permeability

“…1,2,3-Triazolyl alcohol is a positively charged water-soluble alcohol, and its esters with two acidic PAK1-blockers called ursolic acid (UA, a triterpene from rosemary leaves) and ketorolac (a synthetic painkiller) turned out to be both highly cell-permeable and water-soluble, and strongly block PAK1 in cell culture (6,7). Similarly, as summarized in Figures 1 and 2, we have synthesized the 1,2,3-triazolyl esters called 15A and 15C from ARC and CA, respectively, through the "two-step" Click Chemistry, with the relatively high "over-all" yield (around 40% and 25%, respectively), in an attempt to boost the cell-permeability of these two herbal acids abundant in propolis.…”

“…In support of this notion, CAPE, a natural ester of CA, is 10 times more potent to inhibit the cancer growth than CA. More recently, 1,2,3-triazolyl esterization of PAK1-blocking compounds ursolic acid (UA) and ketorolac boosts their anti-cancer activity by 200-fold and 500-fold, respectively (6,7). Accordingly, in this study, through the same Click Chemistry, we have esterized both ARC and CA with 1,2,3-triazolyl alcohol, in an attempt to boost their cell-permeability without loss of their water-solubility.…”