Publications by authors named "Immo Serbian"

16 Publications

  • Page 1 of 1

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

-Propyl 6-amino-2,6-dideoxy-2,2-difluoro-β-d-glucopyranoside is a good inhibitor for the β-galactosidase from .

Med Chem Res 2021 Mar 5:1-9. Epub 2021 Mar 5.

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

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. Especially -propyl 6-amino-2,6-dideoxy-2,2-difluoro-β-d-glucopyranoside () was an excellent competitive inhibitor for the β-galactosidase from holding a of 0.50 μM.
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http://dx.doi.org/10.1007/s00044-021-02715-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934981PMC
March 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

Synthesis and cholinesterase inhibiting potential of A-ring azepano- and 3-amino-3,4-seco-triterpenoids.

Bioorg Chem 2020 08 10;101:104001. Epub 2020 Jun 10.

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

In this study, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives were synthesized from betulin, oleanolic, ursolic and glycyrrhetinic acids aiming to develop new cholinesterase inhibitors. Azepanobetulin, azepanoerythrodiol and azepanouvaol were modified to give amide and tosyl derivatives, while azepano-anhydrobetulines and azepano-glycyrrhetols were obtained for the first time. Oleanane and ursane type 3-amino-3,4-seco-4(23)-en triterpenic alcohols were synthesized by reducing the corresponding 2-cyano-derivatives accessible from Beckmann type 2 rearrangements. The compounds were screened in colorimetric Ellman's assays to determine their ability to act as inhibitors for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum). While most of these compounds were only moderate inhibitors for AChE, several of them were shown to be inhibitors for BChE acting as mixed-type inhibitors. Azepanobetulin 1, its C28-amide derivatives 7 and 8, azepano-11-deoxo-glycyrrhetol 12 and azepanouvaol 18 held inhibition constants K ranging between 0.21 ± 0.06 to 0.68 ± 0.19 μM. Thus, they were approximately 4 to 10 times more active than standard galantamine hydrobromide. For all of the compounds reasonably high docking scores for BChE were obtained being in good agreement with the experimental results from the enzymatic studies. As a result, A-ring azepano-triterpenoids were found to be new scaffolds for the development of BChE inhibitors.
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http://dx.doi.org/10.1016/j.bioorg.2020.104001DOI Listing
August 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

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

Molecules 2020 Apr 23;25(8). Epub 2020 Apr 23.

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

The reactions of phenylglyoxylic acids during the synthesis and biological evaluation of fungal metabolites led to the discovery of hitherto unknown compounds with a -quinone methide (-QM) structure. The formation of these -QMs using C-labelled starting materials revealed a key-step of this reaction being a retro-Friedel-Crafts alkylation.
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http://dx.doi.org/10.3390/molecules25081978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221594PMC
April 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

2-O-(2-chlorobenzoyl) maslinic acid triggers apoptosis in A2780 human ovarian carcinoma cells.

Eur J Med Chem 2019 Oct 16;180:457-464. Epub 2019 Jul 16.

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

Depending on the conditions of the reactions, maslinic acid can be converted into the corresponding 2-O-, 3-O-, or 2,3-di-O-acylated compounds in good yields. These compounds showed in SRB assays a significantly increased cytotoxicity as compared to the parent compound maslinic acid. For the most active compound of this series, i.e. 2-O-(2-chlorobenzoyl) maslinic acid (5), more detailed cell biological tests (i.e. AO/PI dye exclusion experiments, an annexin V assay, and microscopic investigations) on A2780 (human ovarian carcinoma cells) revealed that this compound triggers apoptosis.
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http://dx.doi.org/10.1016/j.ejmech.2019.07.049DOI Listing
October 2019

Synthesis and Biological Evaluation of Structurally Varied 5'-/6'-Isonucleosides and Theobromine-Containing -Isonucleosidyl Derivatives.

Pharmaceuticals (Basel) 2019 Jul 2;12(3). Epub 2019 Jul 2.

Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.

Isonucleosides are rather stable regioisomeric analogs of nucleosides with broad therapeutic potential. We have previously demonstrated the ability of 5' and 6'-isonucleosides to inhibit the activity of acetylcholinesterase, a major target for Alzheimer's disease therapy. Continuing with our research on this topic, we report herein on the synthesis and biological evaluation of a variety of novel terminal isonucleosides and theobromine isonucleotide analogs. Xylofuranose-based purine or uracil 5'-isonucleosides and xylofuranos-5'-yl or glucos-6'-yl theobromine derivatives were accessed via Mitsunobu coupling between partially protected xylofuranose or glucofuranose derivatives with a nucleobase using conventional or microwave-assisted heating conditions. Theobromine-containing -isonucleosidyl sulfonamide and phosphoramidate derivatives were synthesized from isonucleosidyl acetate precursors. The most active compounds in the cholinesterase inhibition assays were a glucopyranose-based theobromine isonucleosidyl acetate, acting as a dual inhibitor of acetylcholinesterase (AChE, = 3.1 µM) and butyrylcholinesterase (BChE, = 5.4 µM), and a 2-,4--bis-xylofuranos-5'-yl uracil derivative, which displayed moderate inhibition of AChE ( = 17.5 µM). Docking studies revealed that the active molecules are positioned at the gorge entrance and at the active site of AChE. None of the compounds revealed cytoxic activity to cancer cells as well as to non-malignant mouse fibroblasts.
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http://dx.doi.org/10.3390/ph12030103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790002PMC
July 2019

Substituted cinnamic anhydrides act as selective inhibitors of acetylcholinesterase.

Bioorg Chem 2019 09 8;90:103058. Epub 2019 Jun 8.

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

Cinnamic anhydrides have been shown to be more than reactive reagents, but they also act as inhibitors of the enzyme acetylcholinesterease (AChE). Thus, out of a set of 33 synthesised derivatives, several of them were mixed type inhibitors for AChE (from electric eel). Thus, (E)-3-(2,4-dimethoxyphenyl)acrylic anhydride (2c) showed K = 8.30 ± 0.94 µM and K' = 9.54 ± 0.38 µM, and for (E)-3-(3-chlorophenyl)acrylic anhydride (2u) K = 8.23 ± 0.93 µM and K' = 13.07 ± 0.46 µM were measured. While being not cytotoxic to many human cell lines, these compounds showed an unprecedented and noteworthy inhibitory effect for AChE but not for butyrylcholinesterase (BChE).
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http://dx.doi.org/10.1016/j.bioorg.2019.103058DOI Listing
September 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

Caffeic acid phenethyl ester (CAPE)-derivatives act as selective inhibitors of acetylcholinesterase.

Eur J Med Chem 2019 Sep 26;177:259-268. Epub 2019 May 26.

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

Unexpected inhibitory effects against eeAChE could be found for a newly synthesized class of caffeic acid phenethyl ester (CAPE) derivatives. Thus, phenethyl-(E)-3-(3,5-dimethoxy-4-phenethoxyphenyl)-acrylate (K = 1.97 ± 0.38 μM, K = 2.44 ± 0.07 μM) and 4-(2-(((E)-3-(3,4-bis(benzyloxy)phenyl)acryloyl)oxy)ethyl)-1,2-phenylene (2E,2'E)-bis(3-(3,4-bis(benzyloxy)phenyl)acrylate) (K = 0.72 ± 0.31 μM, K = 1.80 ± 0.21 μM) showed very good inhibition of eeAChE, while being non cytotoxic for malignant human cancer cells and non-malignant mouse fibroblasts. Also, they are weak inhibitors for BChE (from equine serum).
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http://dx.doi.org/10.1016/j.ejmech.2019.05.059DOI Listing
September 2019

Triterpene-Based Carboxamides Act as Good Inhibitors of Butyrylcholinesterase.

Molecules 2019 Mar 7;24(5). Epub 2019 Mar 7.

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

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)--(2-pyrrolidin-1-ylethyl)-3-acetyloxy-20-oxo-30-norlupan-28-amide () showed a remarkably low K of 0.07 ± 0.01 µM (K' = 2.38 ± 0.48 µM) for the inhibition of BChE.
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http://dx.doi.org/10.3390/molecules24050948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429507PMC
March 2019

An Improved Scalable Synthesis of α- and β-Amyrin.

Molecules 2018 06 27;23(7). Epub 2018 Jun 27.

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

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.
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http://dx.doi.org/10.3390/molecules23071552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100426PMC
June 2018

Converting maslinic acid into an effective inhibitor of acylcholinesterases.

Eur J Med Chem 2015 Oct 9;103:438-45. Epub 2015 Sep 9.

Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany. Electronic address:

During the last decade, maslinic acid has been evaluated for many biological properties, e.g. as an anti-tumor or an anti-viral agent but also as a nutraceutical. The potential of maslinic acid and related derivatives to act as inhibitors of acetyl- or butyryl-cholinesterase was examined in this communication in more detail. Cholinesterases do still represent an interesting group of target enzymes with respect to the investigation and treatment of the Alzheimer's disease and other dementia illnesses as well. Although other triterpenoic acids have successfully been tested for their ability to act as inhibitors of cholinesterases, up to now maslinic acid has not been part of such studies. For this reason, three series of maslinic acid derivatives possessing modifications at different centers were synthesized and subjected to Ellman's assay to determine their inhibitory strength and type of inhibitory action. While parent compound maslinic acid was no inhibitor in these assays, some of the compounds exhibited an inhibition of acetylcholinesterase in the single-digit micro-molar range. Two compounds were identified as inhibitors of butyrylcholinesterase showing inhibition constants comparable to those of galantamine, a drug often used in the treatment of Alzheimer's disease. Furthermore, additional selectivity as well as cytotoxicity studies were performed underlining the potential of several derivatives and qualifying them for further investigations. Docking studies revealed that the different kinetic behavior within the same compound series may be explained by the ability of the compounds to enter the active site gorge of AChE.
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http://dx.doi.org/10.1016/j.ejmech.2015.09.007DOI Listing
October 2015