Terpenoids and especially triterpenoids are the largest and the most diverse group of naturally occurring organic compounds. Its diversity plays very important role in new chemical entities activity screening against different disorders. Some of these compounds and their semi-synthetic derivatives can be identified as potential therapeutics against neurodegenerative diseases and were widely studied in the last few years. Celastrol, oleanolic acid, ursolic acid, asiatic acid, erythrodiol, and some triterpenoid saponins have the ability to protect the brain against neurodegenerative and neuroinflammatory processes. This review article is focused on triterpenoids as possible drugs to treat or slow the progression of neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s Disease (AD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS).

New A-ring or/and C-ring modified methyl oleanolate derivatives were prepared. New simple method of synthesis of 3,12-diketone (333) from methyl oleanonate (22) was worked out. The obtained new compounds were tested for cytotoxic activity on KB, MCF-7 and HeLa cell lines. The derivatives had acetoxy, oxo or hydroxyimino function at the C-3 position and in some cases oxo, hydroxyimino or acyloxyimino group at the C-12 position. Almost all of the compounds showed strong cytotoxic activity, higher than unchanged oleanolic acid. The most active substances turned out to be the derivatives with acyloxyimino function, especially 44 and 8d8d.

Oleanolic acid ketones, oximes, lactams and nitriles were obtained. Complete spectral characterizations (IR, 1H NMR, 13C NMR, DEPT and MS) of the synthesized compounds are presented. The derivatives had oxo, hydroxyimino, lactam or nitrile functions at the C-3 position, an esterified or unmodified carboxyl group at the C-17 location and, in some cases, an additional oxo function at the C-11 position. The new compounds were tested for cytotoxic activity on the HeLa, KB, MCF-7 and Hep-G2 cancer cell lines with the application of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. Among the tested compounds, some oximes and all lactams proved to be the most active cytotoxic agents. These triterpenes significantly inhibited the growth of the HeLa, KB, MCF-7 and Hep-G2 cancer cell lines at micromolar concentrations.