ABSTRACT
Cholic acid (1, CD), deoxycholic (3, DCA), chenodeoxycholic acid (5, CDCA), ursodeoxycholic acid (7, UDCA), and lithocholic acid (9, LCA) were acetylated and converted into their piperazinyl spacered rhodamine B conjugates 16-20. While the parent bile acids showed almost no cytotoxic effects for several human tumor cell lines, the piperazinyl amides were cytostatic but an even superior effect was observed for the rhodamine B conjugates. Extra staining experiments showed these compounds as mitocans; they led to a cell arrest in the G1 phase.
Subject(s)
Bile Acids and Salts , Ursodeoxycholic Acid , Humans , Bile Acids and Salts/pharmacology , Cholic Acid/pharmacology , Ursodeoxycholic Acid/pharmacology , Chenodeoxycholic Acid , Cell Line, Tumor , Deoxycholic Acid/pharmacology , Cholic Acids/pharmacologyABSTRACT
Pentacyclic triterpenoids oleanolic acid, ursolic acid, betulinic acid, and platanic acid were acetylated and converted into several amides 9-31; the cytotoxicity of which has been determined in sulforhodamine B assays employing seral human tumor cell lines and nonmalignant fibroblasts. Thereby, a betulinic acid/trans-1,4-cyclohexyldiamine amide showed excellent cytotoxicity (for example, EC50 = 0.6 µM for HT29 colon adenocarcinoma cells).
Subject(s)
Cyclohexylamines/chemistry , Pentacyclic Triterpenes/pharmacology , Amides/chemistry , Animals , Cell Death/drug effects , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Mice , NIH 3T3 Cells , Pentacyclic Triterpenes/chemistryABSTRACT
3-O-Acetyl-ursolic acid (2) and 3-O-acetyl oleanolic acid (8) were converted into piperazinylamides holding a distal NH, NMe or a NMe2 group. These compounds as well as the corresponding N-methyl-N-oxides were accessed. Their cytotoxicity was assessed in SRB assays employing a panel of human tumor cell lines and non-malignant fibroblasts (NIH 3T3). As a result, compounds holding a quaternary distal N-substituent were less cytotoxic that those holding a NH-moiety. Hence, the presence of a distal cationic center seems not to be a sufficient criterion for obtaining triterpenoids of high cytotoxicity and selectivity.
Subject(s)
Amides/chemistry , Carboxylic Acids/chemistry , Cytotoxins/chemistry , Cytotoxins/toxicity , Triterpenes/chemistry , Triterpenes/toxicity , Animals , Cell Line, Tumor , Humans , Mice , NIH 3T3 Cells , Structure-Activity RelationshipABSTRACT
Several triterpenoid acids (betulinic, oleanolic, ursolic, glycyrrhetinic) and triterpene betulin were used as starting material to synthesize BODIPY FL adducts, and these compounds were screened for their cytotoxic activity employing several human tumor cell lines. The cytotoxicity of the compounds strongly depended on the chosen spacer between the triterpenoid core and the BODIPY FL unit. Thus, 3-O-acetyl-betulinic acid derived BODIPY FL conjugate holding an ethylendiamine spacer was cytotoxic for human breast adenocarcinoma cells MCF7 but not cytotoxic for all other cell lines.
