Affiliation: Martin Luther University
- Sommerwerk S, Heller L, Siewert B, Csuk R. Chemoenzymatic synthesis and cytotoxicity of oenanthotoxin and analogues. Bioorg Med Chem. 2015;23:5595-602 pubmed publisher..Oenanthotoxin and many derivatives thereof were cytotoxic to tumor cell lines as well as to non-malignant mouse fibroblasts. The highest activity was determined for human ovarian cancer cells A2780 with EC50 = 3.8 Î¼M. ..
- Serbian I, Csuk R. An Improved Scalable Synthesis of α- and β-Amyrin. Molecules. 2018;23: pubmed publisher..For α-amyrin, a different synthetic approach had to be chosen providing access to α-amyrin in medium-to-large scale. ..
- Wiemann J, Heller L, Csuk R. An access to a library of novel triterpene derivatives with a promising pharmacological potential by Ugi and Passerini multicomponent reactions. Eur J Med Chem. 2018;150:176-194 pubmed publisher..Especially, the MA-Ugi products 6a, 6b and 7b showed a remarkable cytotoxicity for A2780 ovarian carcinoma cells in a low Î¼M range. Compounds 6a and 7b induced programmed cell death in part through the apoptosis pathway. ..
- Heller L, Obernauer A, Csuk R. Simple structural modifications confer cytotoxicity to allobetulin. Bioorg Med Chem. 2015;23:3002-12 pubmed publisher..Their selectivity to distinguish between cancer cell and non-malignant cell depends on the configuration at position C-3. ..
- Schwarz S, Loesche A, Lucas S, Sommerwerk S, Serbian I, Siewert B, et al. Converting maslinic acid into an effective inhibitor of acylcholinesterases. Eur J Med Chem. 2015;103:438-45 pubmed publisher..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. ..
- Heller L, Schwarz S, Obernauer A, Csuk R. Allobetulin derived seco-oleananedicarboxylates act as inhibitors of acetylcholinesterase. Bioorg Med Chem Lett. 2015;25:2654-6 pubmed publisher..A dibutenylester of low cytotoxicity (NIH 3T3 murine embryonic fibroblasts) was shown to be a good mixed-type inhibitor (Ki=3.39, Ki'=2.26Î¼M) for acetylcholinesterase. ..
- Wolfram R, Heller L, Csuk R. Targeting mitochondria: Esters of rhodamine B with triterpenoids are mitocanic triggers of apoptosis. Eur J Med Chem. 2018;152:21-30 pubmed publisher..Staining experiments combined with fluorescence microscopy showed that this compound triggered apoptosis in A2780 ovarian carcinoma cells and acted as a mitocan. ..
- Csuk R, Barthel Niesen A, Barthel A, SchÃ¤fer R, Al Harrasi A. 11-Keto-boswellic acid derived amides and monodesmosidic saponins induce apoptosis in breast and cervical cancers cells. Eur J Med Chem. 2015;100:98-105 pubmed publisher..The most active compound of this series gave IC50 values as low as 4.5Â Î¼M. Cell death proceeded mainly via apoptosis. ..
- Csuk R, Niesen Barthel A, SchÃ¤fer R, Barthel A, Al Harrasi A. Synthesis and antitumor activity of ring A modified 11-keto-Î²-boswellic acid derivatives. Eur J Med Chem. 2015;92:700-11 pubmed publisher..Thus, the introduction of an amino group at position C-2 led to a significantly improved cytotoxic activity of amine 18. An apoptotic effect of compound 18 was determined using DNA laddering and trypan blue staining experiments. ..
- Sommerwerk S, Heller L, Kerzig C, Kramell A, Csuk R. Rhodamine B conjugates of triterpenoic acids are cytotoxic mitocans even at nanomolar concentrations. Eur J Med Chem. 2017;127:1-9 pubmed publisher..Compound 24 (a diacetylated maslinic acid derivative) was most toxic for several human tumor cell lines but less toxic for mouse fibroblasts NIH 3T3. Staining and double-staining experiments revealed 24 to act as a mitocan. ..
- Loesche A, Wiese J, Sommerwerk S, Simon V, Brandt W, Csuk R. Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected class of potent inhibitors of cholinesterases. Eur J Med Chem. 2017;125:430-434 pubmed publisher..Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide. ..
- Heller L, Kahnt M, Loesche A, Grabandt P, Schwarz S, Brandt W, et al. Amino derivatives of platanic acid act as selective and potent inhibitors of butyrylcholinesterase. Eur J Med Chem. 2017;126:652-668 pubmed publisher..01 ± 0.003 ?M for BChE. This compound proved to be a selective (FB = 851), mixed-type inhibitor for BChE. ..
- Sommerwerk S, Heller L, Kuhfs J, Csuk R. Selective killing of cancer cells with triterpenoic acid amides - The substantial role of an aromatic moiety alignment. Eur J Med Chem. 2016;122:452-464 pubmed publisher..As shown by additional experiments (acridine orange/propidium iodide staining, fluorescence spectroscopy and cell cycle investigations) these compounds act mainly by apoptosis. ..
- Sommerwerk S, Heller L, Kuhfs J, Csuk R. Urea derivates of ursolic, oleanolic and maslinic acid induce apoptosis and are selective cytotoxic for several human tumor cell lines. Eur J Med Chem. 2016;119:1-16 pubmed publisher..9 ?M (for A2780 ovarian cancer cells) with EC50 > 120 ?M for fibroblasts (NIH 3T3) and triggered apoptosis while caspase-3 was not activated by this compound. ..
- Rodríguez Hernández D, Demuner A, Barbosa L, Heller L, Csuk R. Novel hederagenin-triazolyl derivatives as potential anti-cancer agents. Eur J Med Chem. 2016;115:257-67 pubmed publisher..Compounds 4, 8 and 15 were the most potent against all human cancer cell lines. Furthermore, compound 11 was the most cytotoxic against cell HT29 showing EC50 = 1.6 ?M and a selectivity index of 5.4. ..
- Wiemann J, Heller L, Perl V, Kluge R, StrÃ¶hl D, Csuk R. Betulinic acid derived hydroxamates and betulin derived carbamates are interesting scaffolds for the synthesis of novel cytotoxic compounds. Eur J Med Chem. 2015;106:194-210 pubmed publisher..Hexyl substituted 39 showed EC50 = 5.6 Î¼M (518A2 cells) while for mouse fibroblasts EC50 > 30 was determined. ..
- RodrÃguez HernÃ¡ndez D, Demuner A, Barbosa L, Csuk R, Heller L. Hederagenin as a triterpene template for the development of new antitumor compounds. Eur J Med Chem. 2015;105:57-62 pubmed publisher..1-6.5Â Î¼M for six human cancer cell lines. Notably, this corresponds to an approximately 30-fold times greater potency than He. ..
- Heller L, Knorrscheidt A, Flemming F, Wiemann J, Sommerwerk S, Pavel I, et al. Synthesis and proapoptotic activity of oleanolic acid derived amides. Bioorg Chem. 2016;68:137-51 pubmed publisher..Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis. ..
- Nain Perez A, Barbosa L, Rodríguez Hernández D, Kramell A, Heller L, Csuk R. Natural abenquines and synthetic analogues: Preliminary exploration of their cytotoxic activity. Bioorg Med Chem Lett. 2017;27:1141-1144 pubmed publisher..6 and 0.8?M respectively. Likewise, the analogues 2i, 3f and 3g showed strong activity against cell HT29 with EC50=0.9?M for these compounds. ..
- Wiemann J, Loesche A, Csuk R. Novel dehydroabietylamine derivatives as potent inhibitors of acetylcholinesterase. Bioorg Chem. 2017;74:145-157 pubmed publisher..Particularly N-benzoyldehydroabietylamines 11, 12 and 13 were excellent inhibitors for AChE, showing inhibition rates comparable to standard galantamine hydrobromide. ..
- Wiemann J, Karasch J, Loesche A, Heller L, Brandt W, Csuk R. Piperlongumine B and analogs are promising and selective inhibitors for acetylcholinesterase. Eur J Med Chem. 2017;139:222-231 pubmed publisher..These compounds may be regarded as promising candidates for the development of efficient inhibitors of acetylcholinesterase being useful for the treatment of Alzheimer's disease. ..
- Rodríguez Hernández D, Barbosa L, Demuner A, Nain Perez A, Ferreira S, Fujiwara R, et al. Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives. Eur J Med Chem. 2017;140:624-635 pubmed publisher..In addition, hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding site of the enzyme CYP51Li...
- Kahnt M, Heller L, Grabandt P, Al Harrasi A, Csuk R. Platanic acid: A new scaffold for the synthesis of cytotoxic agents. Eur J Med Chem. 2018;143:259-265 pubmed publisher..Compound 17, a methyl (3?, 20R) 3-acetyloxy-20-amino-30-norlupan-28-oate, induced apoptosis in A2780 ovarian carcinoma cells. ..
- Csuk R, Schwarz S, Kluge R, Ströhl D. Synthesis and biological activity of some antitumor active derivatives from glycyrrhetinic acid. Eur J Med Chem. 2010;45:5718-23 pubmed publisher..The most compound 7 possesses an aminohexyl side chain, induces apoptosis and shows IC50 values of 0.6-3.0 ?M. ..
- Wiemann J, Heller L, Csuk R. Targeting cancer cells with oleanolic and ursolic acid derived hydroxamates. Bioorg Med Chem Lett. 2016;26:907-909 pubmed publisher..3 Î¼M), A2780 (ovarian carcinoma, EC50=3.4 Î¼M) and HT29 (colon adenocarcinoma, EC50=5.6 Î¼M) while being significantly less cytotoxic for fibroblasts (EC50=20.4 Î¼M). ..
- Csuk R, Stark S, Nitsche C, Barthel A, Siewert B. Alkylidene branched lupane derivatives: synthesis and antitumor activity. Eur J Med Chem. 2012;53:337-45 pubmed publisher..Cytotoxicity can be improved by encapsulation in liposomes. These compounds act by triggering apoptotic cell death as shown by DNA-laddering experiments and acridine orange/ethidium bromide staining. ..