Publications by authors named "Sophie Hoenke"

14 Publications

  • Page 1 of 1

Type and position of linkage govern the cytotoxicity of oleanolic acid rhodamine B hybrids.

Steroids 2021 Jun 12;172:108876. Epub 2021 Jun 12.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle, Saale, Germany. Electronic address:

Oleanolic acid/rhodamine B hybrids exhibit different cytotoxicity depending on the way these two structural elements are linked. While a hybrid holding a piperazinyl spacer at C-28 proved to be cytotoxic in the nano-molar concentration range, hybrids with a direct linkage of the Rho B residue to C-3 of the triterpenoid skeleton are cytotoxic only in the low micro-molar concentration range without any selectivity. This once again underlines the importance of selecting the right spacer and the most appropriate position on the skeleton of the triterpene to achieve the most cytotoxic hybrids possible.
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http://dx.doi.org/10.1016/j.steroids.2021.108876DOI Listing
June 2021

Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential.

Nat Prod Res 2021 May 10:1-10. Epub 2021 May 10.

Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.

The chalcone derivatives of 20-oxo-lupanes have been synthesised and screened for some types of biological activity. Ozonolysis of lupanes afforded 20-oxo-derivatives with the following condensation using different aromatic aldehydes by Claisen‒Schmidt reaction to the target compounds. The configuration of 19-[3-(pyridin-3-yl)-prop-2-en-1-one]-fragment was established by X-ray analysis. Screening of cytotoxic activity against NCI-60 cancer cell line panel revealed, that messagenin derivative has the highest activity with GI value ranged from 0.304 to 0.804 μM. A colorimetric SRB assay revealed for the 2,30-bis-furfurylidene derivative and 30-bromo-20-oxo-29-nor-3,28-diacetoxy-betulin cytotoxic activity against breast carcinoma MCF-7 and ovarian carcinoma A2780 cell lines. Compounds and acted also as inhibitors of the enzyme -glucosidase (from ) with IC values of 1.76 μM and 3.3 μM thus being 97- and 52-fold more active than standard acarbose. Antiviral potency of compounds and against HCMV, HSV-1 and HPV is also discussed.
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http://dx.doi.org/10.1080/14786419.2021.1922904DOI Listing
May 2021

A simple but unusual rearrangement of an oleanane to a taraxerane-28,14 β -olide.

Steroids 2021 Apr 27;172:108853. Epub 2021 Apr 27.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address:

Reaction of 3-O-acetyl-oleanolic acid (3) with formic acid/hydrogen peroxide at 100 °C for several hours provides an extraordinary but simple pathway to a taraxeran-28,14 β -olide type triterpenoid while the same reaction at 0 °C occurred without re-arrangement of the carbon skeleton, and an oleanane-28,13 β -olide was obtained instead. The products from these reactions were subjected to a cytotoxicity screening employing several human tumor cell lines showing the latter compound not cytotoxic while the former was cytotoxic especially for MCF-7 (breast adenocarcinoma), and FaDu (hypopharyngeal carcinoma) cells. The highest cytotoxicity, however, was observed for 3 β, 12α, 13 β -trihydroxy-oleanan-28-oic acid (6) holding with EC = 4.2 μM for MCF-7 tumor cells.
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http://dx.doi.org/10.1016/j.steroids.2021.108853DOI Listing
April 2021

The Presence of a Cyclohexyldiamine Moiety Confers Cytotoxicity to Pentacyclic Triterpenoids.

Molecules 2021 Apr 6;26(7). Epub 2021 Apr 6.

Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes, Str. 2, D-06120 Halle (Saale), Germany.

Pentacyclic triterpenoids oleanolic acid, ursolic acid, betulinic acid, and platanic acid were acetylated and converted into several amides -; the cytotoxicity of which has been determined in sulforhodamine B assays employing seral human tumor cell lines and nonmalignant fibroblasts. Thereby, a betulinic acid/-1,4-cyclohexyldiamine amide showed excellent cytotoxicity (for example, EC = 0.6 μM for HT29 colon adenocarcinoma cells).
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http://dx.doi.org/10.3390/molecules26072102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038856PMC
April 2021

Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids.

Int J Mol Sci 2021 Feb 8;22(4). Epub 2021 Feb 8.

Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.

Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds , , , , , , , , , and showed growth inhibitory (GI) against the most sensitive cell lines at submicromolar concentrations (0.20-0.94 μM), and their cytotoxic activity (LC) was also high (1-6 μM). Derivatives , , , , and demonstrated a certain selectivity profile at GI level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.
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http://dx.doi.org/10.3390/ijms22041714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914897PMC
February 2021

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates.

Molecules 2020 Nov 20;25(22). Epub 2020 Nov 20.

Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes Street 2, D-06120 Halle, Germany.

The combination of the "correct" triterpenoid, the "correct" spacer and rhodamine B () 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 EC 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 conjugate , holding a homopiperazinyl spacer can be regarded, at present, as the most promising candidate for further biological studies.
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http://dx.doi.org/10.3390/molecules25225443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699795PMC
November 2020

Cytotoxic triterpenoid-safirinium conjugates target the endoplasmic reticulum.

Eur J Med Chem 2021 Jan 8;209:112920. Epub 2020 Oct 8.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle, Saale, Germany. Electronic address:

Safirinium P and Q fluorescence labels were synthesized and conjugated with spacered triterpenoic acids to access hybrid structures. While the parent safirinium compounds were not cytotoxic at all, many triterpenoid safirinium P and Q conjugates showed moderate cytotoxicity. An exception, however, was safirinium P derived compound 30 holding low EC = 5.4 μM (for A375 cells) to EC = 7.5 μM (for FaDu cells) as well as EC = 6.6 μM for non-malignant fibroblasts NIH 3T3. Fluorescence imaging showed that the safirinium core structures cannot enter the cells (not even after a prolonged incubation time of 24 h), while the conjugates (as exemplified for 30) are accumulating in the endoplasmic reticulum but not in the mitochondria. The development of safirinium-hybrids targeting the endoplasmic reticulum can be regarded as a promising strategy in the development of cytotoxic agents.
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http://dx.doi.org/10.1016/j.ejmech.2020.112920DOI Listing
January 2021

Betulinic acid derived amides are highly cytotoxic, apoptotic and selective.

Eur J Med Chem 2020 Dec 9;207:112815. Epub 2020 Sep 9.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), Germany. Electronic address:

Betulinic and platanic acid derived amides were prepared and screened for their cytotoxic activity. All of the compounds were shown to be cytotoxic for a panel of human tumor cell lines, and especially apoptotic betulinic acid derived compounds 6, 8 and 19 showed low EC values. Of special interest was a 4-isoquinolinyl amide of 3-O-acetyl-betulinic acid (compound 19), being the most cytotoxic compound of this series and holding EC values as low as EC = 1.48 μM (A375 melanoma cells) while being significantly less cytotoxic for non-malignant fibroblasts NIH 3T3 with a selectivity index of >91.2. This finding parallels previous results obtained for SAA21, a augustic acid derived compound thus making the 4-isoquinolinyl moiety to a privileged scaffold.
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http://dx.doi.org/10.1016/j.ejmech.2020.112815DOI Listing
December 2020

The presence of a cationic center is not alone decisive for the cytotoxicity of triterpene carboxylic acid amides.

Steroids 2020 11 12;163:108713. Epub 2020 Aug 12.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.

3-O-Acetyl-ursolic acid (2) and 3-O-acetyl oleanolic acid (8) were converted into piperazinylamides holding a distal NH, NMe or a NMe 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.
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http://dx.doi.org/10.1016/j.steroids.2020.108713DOI Listing
November 2020

Synthesis of some steroidal mitocans of nanomolar cytotoxicity acting by apoptosis.

Eur J Med Chem 2020 Aug 11;199:112425. Epub 2020 May 11.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle (Saale), Germany. Electronic address:

Several steroids (abiraterone, prednisone, testosterone, cholesterol) and the BCL-2 inhibitor bexarotene were used as starting materials to synthesize iperazinyl-spacered rhodamine B conjugates. The conjugates were screened for their cytotoxicity in SRB assays against several human tumor cell lines and found to be active in a low μM to nM range. The conjugate derived from testosterone held an EC = 59 nM against MCF-7 tumor cells and acted mainly by necrosis. The prednisone conjugate, however, was less cytotoxic but acted mainly by apoptosis and held a moderate selectivity against MCF-7 tumor cells.
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http://dx.doi.org/10.1016/j.ejmech.2020.112425DOI Listing
August 2020

Design, synthesis and cytotoxicity of BODIPY FL labelled triterpenoids.

Eur J Med Chem 2020 Jan 6;185:111858. Epub 2019 Nov 6.

Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle, Saale, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ejmech.2019.111858DOI Listing
January 2020

Ureidobenzenesulfonamides as efficient inhibitors of carbonic anhydrase II.

Bioorg Chem 2019 10 17;91:103123. Epub 2019 Jul 17.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address:

Sulfonamides represent an important class of drugs because of their inhibitory effect on carbonic anhydrases (CAs). We therefore synthesized several ureidobenzenesulfonamides and evaluated their bCA II inhibition for their potential use as anti-glaucoma gents. Since these compounds must not show cytotoxic effects, their cytotoxic potential against several human tumor cell lines and non-malignant fibroblasts was investigated. Several fluorophenyl substituted sulfonamides were efficient inhibitors of bCA II. Only one benzylphenyl substituted sulfonamide, however, showed a remarkable selectivity for HT29 colorectal carcinoma cells while being significantly less cytotoxic to non-malignant fibroblasts.
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http://dx.doi.org/10.1016/j.bioorg.2019.103123DOI Listing
October 2019

Synthesis and Cytotoxicity Evaluation of DOTA-Conjugates of Ursolic Acid.

Molecules 2019 Jun 17;24(12). Epub 2019 Jun 17.

Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.

In this study, we report the synthesis of several amine-spacered conjugates of ursolic acid (UA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Thus, a total of 11 UA-DOTA conjugates were prepared holding various oligo-methylene diamine spacers as well as different substituents at the acetate units of DOTA including -butyl, benzyl, and allyl esters. Furthermore, three synthetic approaches were compared for the ethylenediamine-spacered conjugate regarding reaction steps, yields, and precursor availability. The prepared conjugates were investigated regarding cytotoxicity using SRB assays and a set of human tumor cell lines. The highest cytotoxicity was observed for piperazinyl spacered compound . Thereby, EC values of 1.5 µM (for A375 melanoma) and 1.7 µM (for A2780 ovarian carcinoma) were determined. Conjugates and were selected for further cytotoxicity investigations including fluorescence microscopy, annexin V assays and cell cycle analysis.
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http://dx.doi.org/10.3390/molecules24122254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630699PMC
June 2019

The cytotoxicity of oleanane derived aminocarboxamides depends on their aminoalkyl substituents.

Steroids 2019 09 6;149:108422. Epub 2019 Jun 6.

Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address:

Several oligo-methylene diamine derived carboxamides of oleanolic and maslinic acid have been prepared, and substitutions of the terminal primary amine as well as variations of the length of alkyl chain of the diamine moiety were made. Biological evaluation of their cytotoxic activity was performed using photometric sulforhodamin B assays employing a panel of different human cancer cell lines. These experiments showed most of the carboxamides to be cytotoxic with EC values below 10 µM. Prolongation of the alkyl chain length initially reduced EC values to a minimum, but a decrease in cytotoxicity was observed for longer alkyl chains. Variation of substituents at the terminal nitrogen atom, however, did not influence EC values at all. Noteworthy results were obtained particularly for compounds 4, 6 and 23 as indicated by EC values lower than 2 µM, and in case of a maslinic derivative 23 even an increased tumor/non-tumor cell selectivity was observed. These compounds were further investigated using fluorescence microscopy and flow cytometry analysis, which revealed 6 to show indications of apoptosis.
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http://dx.doi.org/10.1016/j.steroids.2019.05.014DOI Listing
September 2019