Abstract
Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4–10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11–17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.
Highlights
Asiatic acid (AA, 2α,3β,23-trihydroxyurs-12-ene-28-oic acid, Figure 1), one of the active pentacyclic triterpenoids found in Centalla asiatica, can be prepared from hydrolysis of asiaticoside
Poly(L-lactide) (PLLA) nanoparticles loaded with asiatic acid (AA) have been successfully produced using the rapid expansion of a subcritical solution into an aqueous receiving solution containing a dispersing agent [12]
Reaction of 3 with concentrated Et3N solution and amino acid methyl ester hydrochlorides furnished amides 4–10, which were hydrolyzed with aqueous NaOH to give asiatic amides 11–17 (Scheme 1)
Summary
Asiatic acid (AA, 2α,3β,23-trihydroxyurs-12-ene-28-oic acid, Figure 1), one of the active pentacyclic triterpenoids found in Centalla asiatica, can be prepared from hydrolysis of asiaticoside. Molecules 2015, 20 its traditional usage to treat skin defects [1], AA has other biological effects including anti-tumor [2,3,4,5,6], anti-inflammation [7], hepatoprotective [8], anti-depression, and anti-Alzheimer’s disease [9,10]. 2-hydroxypropyl-β-cyclodextrin has been used as an adjuvant for enhancing the encapsulation and releasing characteristics of asiaticoside [11]. Poly(L-lactide) (PLLA) nanoparticles loaded with asiatic acid (AA) have been successfully produced using the rapid expansion of a subcritical solution into an aqueous receiving solution containing a dispersing agent [12]. Many researchers have synthesized various AA derivatives by adding new groups to AA [13,14,15]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call