Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection

Abstract

3beta-Hydroxy-lup-20(29)-en-28-oic acid (betulinic acid) is a pentacyclic lupane-type triterpene that is widely distributed throughout the plant kingdom. A variety of biological activities have been ascribed to betulinic acid including anti-inflammatory and in vitro antimalarial effects. However, betulinic acid is most highly regarded for its anti-HIV-1 activity and specific cytotoxicity against a variety of tumor cell lines. Interest in developing even more potent anti-HIV agents based on betulinic acid has led to the discovery of a host of highly active derivatives exhibiting greater potencies and better therapeutic indices than some current clinical anti-HIV agents. While its mechanism of action has not been fully determined, it has been shown that some betulinic acid analogs disrupt viral fusion to the cell in a post-binding step through interaction with the viral glycoprotein gp41 whereas others disrupt assembly and budding of the HIV-1 virus. With regard to its anticancer properties, betulinic acid was previously reported to exhibit selective cytotoxicity against several melanoma-derived cell lines. However, more recent work has demonstrated that betulinic acid is cytotoxic against other non-melanoma (neuroectodermal and malignant brain tumor) human tumor varieties. Betulinic acid appears to function by means of inducing apoptosis in cells irrespective of their p53 status. Because of its selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of HIV infection and cancer.

Chemical constituents from Tabernaemontana catharinensis root bark: a brief NMR review of indole alkaloids and in vitro cytotoxicity

“…The compounds at the concentration tested in this work against human tumor cell lines do not shown significant cytotoxic activity on pheripheral blood mononuclear cells (data not shown). This observations is in agreement with observations that lupane type triterpenes as betulinic acid presents selective cytotoxicity against tumor cells and favorable therapeutic index, even at doses up to 500 mg/kg body weight, betulinic acid is a very promising new chemotherapeutic agent for the treatment of cancer 20,21 . The triterpenes cytotoxic activity mechanisms on tumor cells remains unclear.…”

The Lupane-type Triterpene 30-Oxo-calenduladiol Is a CCR5 Antagonist with Anti-HIV-1 and Anti-chemotactic Activities

“…In this matter, pentacyclic triterpenes represent a varied class of natural products presenting antitumor and antiviral activities (7)(8)(9). A well studied pentacyclic lupane-type triterpene is the betulinic acid (3␤-hydroxy-lup-20(29)-en-28-oic acid), widely distributed throughout the plant kingdom, which presents anti-inflammatory, anti-malarial, and anti-HIV-1 effects in vitro (7,9,10). Although its mechanism of action has not been fully determined, it has been reported that some lupane-type triterpene derivatives impair HIV-1 fusion through interacting with the viral glycoprotein gp41, or disrupting the assembly and budding of emerging viral particles in infected target cells (reviewed in Ref.…”

Update: Biological and Chemical Aspects of Senna spectabilis

“…5,31,[63][64][65] Commonly known as 3β-hydroxy-lup-20-(29)-en-28-oic acid, this triterpene promises to be a potential drug for cancer treatment due to its cytotoxicity against various cancer cell lines (lung, ovarian, neuroand glioblastoma and head/neck carcinomas), selective inhibition of human melanoma, apoptosis induction in human neurobastoma and low toxicity to healthy cells. 66 Ursolic acid, found either free or bounded to saponins, is a common constituent of fruits from human diet such as apple, guava and blueberry. 31,67 Known as 3β-hydroxy-urs-12-en-28-oic-acid, this metabolite has protective properties against fatty liver induced by high-lipid diet and liver injury as well as anti-bacterial, anti-inflammatory and antioxidative properties.…”