Quaternary ammonium derivatives of natural terpenoids. Synthesis and properties

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

“…This effect fosters the accumulation of cationic molecules [ 17 , 47 , 48 ], hence inducing high selectivity for mitocans holding a (more or less) lipophilic cation such as a rhodamine scaffold. The same effect applies for triphenylphosphonium cations [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ] and to a small extent for quaternary ammonium ions [ 58 , 59 , 60 ], zwitterionic N -oxides [ 60 , 61 ] and triterpenes substituted with BODIPYs [ 62 , 63 , 64 , 65 , 66 ] or a safirinium moiety [ 67 ]. However, the presence of a cationic center is not alone decisive for achieving high cytotoxic effects [ 60 ].…”

One-pot synthesis of quaternary pyridinium salts of lupane triterpenoids and their antimicrobial properties

“…6,7 Natural triterpenoids are successfully used as amphiphilic molecules, since they have low toxicity and a high affinity for phospholipid membranes. 8 The major disadvantage that hinders the use of all known terpenoid analogs as drugs is low bioavailability associated with poor solubility in biological fluids, which limits their effective interaction with biological targets. 9,10 This problem could be solved by introducing polar groups, including ammonium moieties.…”

Synthesis and cytotoxic evaluation of malachite green derived oleanolic and ursolic acid piperazineamides

“…Some of these transporters were reported to be overexpressed in malignant cells (Cai et al 2014;Cai et al 2016;Everett et al 2013). Several molecules holding a cationic residue are cytotoxic and seem to target the mitochondria, such as ammonium (Biedermann et al 2010;Kataev et al 2014) or phosphonium salts (Spivak et al 2013(Spivak et al , 2017) of more complex molecules. Thus, these compounds are mitocans ("mitochondrially targeted anticancer drugs").…”

“…Thus, hybrids holding an extra cationic functional group have shown promising to excellent cytotoxic results. While "simple" quaternary ammonium salts (Biedermann et al 2010;Kataev, Strobykina, and Zakharova 2014) were only of moderate cytotoxicity with their EC 50 values being in the same potency range as phosphonium salts (Spivak et al 2017(Spivak et al , 2013, hybrids consisting of a suitable pentacyclic triterpene, an amine spacer and a BODIPY-FL group (Brandes et al 2020;Krajcovicova et al 2018) held lower EC 50 values against a variety of different human cancer cell lines. Superior cytotoxicity, however, was found for those triterpenoids holding one or two O-acetyl groups on ring A, an amide spacer at C-28 (preferentially a piperazinyl residue), and a rhodamine B moiety attached to this spacer (Sommerwerk et al 2017).…”