An Improved Scalable Synthesis of α- and β-Amyrin

The synthesis of α- and β-amyrin was accomplished starting from easily accessible starting materials, oleanolic, and ursolic acid. The procedures allow the preparation of β-amyrin in an exceptionally short scalable manner via selective iodation and reduction. For α-amyrin, a different synthetic approach had to be chosen providing access to α-amyrin in medium-to-large scale

Ester and amide derivatives of rhodamine B exert cytotoxic effects on different human tumor cell lines

<jats:title>Abstract</jats:title><jats:p>Three esters of rhodamine B (<jats:bold>1</jats:bold>–<jats:bold>3</jats:bold>) differing in their alkyl chain lengths as well as several rhodamine B amides (<jats:bold>4</jats:bold>–<jats:bold>9</jats:bold>) were synthesized in good yields and tested for their cytotoxicity in SRB assays employing several human tumor cell lines. The rhodamine B esters were unselective but showed cytotoxicity of as low as EC<jats:sub>50</jats:sub> = 0.15 ± 0.02 µM. The rhodamine B amides were slightly less cytotoxic but showed good selectivity against MCF-7 and A2780 tumor cell lines. Especially a morpholinyl derivative <jats:bold>4</jats:bold> was ~20 time more cytotoxic for MCF-7 than for nonmalignant NIH 3T3 cells.</jats:p&gt

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

The combination of the “correct” triterpenoid, the “correct” spacer and rhodamine B (RhoB) seems to be decisive for the ability of the conjugate to accumulate in mitochondria. So far, several triterpenoid rhodamine B conjugates have been prepared and screened for their cytotoxic activity. To obtain cytotoxic compounds with EC50 values in a low nano-molar range combined with good tumor/non-tumor selectivity, the Rho B unit has to be attached via an amine spacer to the terpenoid skeleton. To avoid spirolactamization, secondary amines have to be used. First results indicate that a homopiperazinyl spacer is superior to a piperazinyl spacer. Hybrids derived from maslinic acid or tormentic acid are superior to those from oleanolic, ursolic, glycyrrhetinic or euscaphic acid. Thus, a tormentic acid-derived RhoB conjugate 32, holding a homopiperazinyl spacer can be regarded, at present, as the most promising candidate for further biological studies

Triterpene-Based Carboxamides Act as Good Inhibitors of Butyrylcholinesterase

A set of overall 40 carboxamides was prepared from five different natural occurring triterpenoids including oleanolic, ursolic, maslinic, betulinic, and platanic acid. All of which were derived from ethylene diamine holding an additional substituent connected to the ethylene diamine group. These derivatives were evaluated regarding their inhibitory activity of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) employing Ellman’s assay. We further determined the type of inhibition and inhibition constants. Carboxamides derived from platanic acid have been shown to be potent and selective BChE inhibitors. Especially the mixed-type inhibitor (3β)-N-(2-pyrrolidin-1-ylethyl)-3-acetyloxy-20-oxo-30-norlupan-28-amide (35) showed a remarkably low Ki of 0.07 ± 0.01 µM (Ki′ = 2.38 ± 0.48 µM) for the inhibition of BChE

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

<jats:title>Abstract</jats:title><jats:p>The coupling of acetylated piperazinylamide spacered triterpenoic oleanolic acid and ursolic acid with<jats:italic>meta</jats:italic>or<jats:italic>para</jats:italic>substituted carboxylated malachite green analogs gave conjugates<jats:bold>10</jats:bold>,<jats:bold>11</jats:bold>,<jats:bold>15</jats:bold>, and<jats:bold>16</jats:bold>that were cytotoxic for several human tumor cell lines. Especially, an oleanolic acid-derived compound<jats:bold>10</jats:bold>was cytotoxic for MCF-7 human breast carcinoma cells (EC<jats:sub>50</jats:sub> = 0.7 μM). These derivatives represent first examples of triterpenoic acid derivatives holding a cationic scaffold derived from malachite green.</jats:p&gt

Madecassic Acid—A New Scaffold for Highly Cytotoxic Agents

Due to their manifold biological activities, natural products such as triterpenoids have advanced to represent excellent leading structures for the development of new drugs. For this reason, we focused on the syntheses and cytotoxic evaluation of derivatives obtained from gypsogenin, hederagenin, and madecassic acid, cytotoxicity increased—by and large—from the parent compounds to their acetates. Another increase in cytotoxicity was observed for the acetylated amides (phenyl, benzyl, piperazinyl, and homopiperazinyl), but a superior cytotoxicity was observed for the corresponding rhodamine B conjugates derived from the (homo)-piperazinyl amides. In particular, a madecassic acid homopiperazinyl rhodamine B conjugate 24 held excellent cytotoxicity and selectivity for several human tumor cell lines. Thus, this compound was more than 10,000 times more cytotoxic than parent madecassic acid for A2780 ovarian cancer cells. We assume that the presence of an additional hydroxyl group at position C–6 in derivatives of madecassic, as well as the (2α, 3β) configuration of the acetates in ring A, had a beneficial effect onto the cytotoxicity of the conjugates, as well as onto tumor/non-tumor cell selectivity

n-Propyl 6-amino-2,6-dideoxy-2,2-difluoro-β-D-glucopyranoside is a good inhibitor for the β-galactosidase from E. coli

A convenient route has been developed for the synthesis of novel 6-amino-2,2-(or 3,3-difluoro)-2-(or 3),6-dideoxy-hexopyranoses. Biological screening showed these compounds as good inhibitors for several glycosidases. Especiall

Rhodamine 101 Conjugates of Triterpenoic Amides Are of Comparable Cytotoxicity as Their Rhodamine B Analogs

Pentacyclic triterpenoic acids (betulinic, oleanolic, ursolic, and platanic acid) were selected and subjected to acetylation followed by the formation of amides derived from either piperazine or homopiperazine. These amides were coupled with either rhodamine B or rhodamine 101. All of these compounds were screened for their cytotoxic activity in SRB assays. As a result, the cytotoxicity of the parent acids was low but increased slightly upon their acetylation while a significant increase in cytotoxicity was observed for piperazinyl and homopiperazinyl amides. A tremendous improvement in cytotoxicity was observed; however, for the rhodamine B and rhodamine 101 conjugates, and compound 27, an ursolic acid derived homopiperazinyl amide holding a rhodamine 101 residue showed an EC50 = 0.05 µM for A2780 ovarian cancer cells while being less cytotoxic for non-malignant fibroblasts. To date, the rhodamine 101 derivatives presented here are the first examples of triterpene derivatives holding a rhodamine residue different from rhodamine B

In the Mists of a Fungal Metabolite: An Unexpected Reaction of 2,4,5-Trimethoxyphenylglyoxylic Acid

The reactions of phenylglyoxylic acids during the synthesis and biological evaluation of fungal metabolites led to the discovery of hitherto unknown compounds with a p-quinone methide (p-QM) structure. The formation of these p-QMs using 13C-labelled starting materials revealed a key-step of this reaction being a retro-Friedel–Crafts alkylation