The Presence of a Cyclohexyldiamine Moiety Confers Cytotoxicity to Pentacyclic Triterpenoids

Hoenke, Sophie; Christoph, Martin A; Friedrich, Sander; Heise, Niels V.; Brandes, Benjamin; Deigner, Hans‐Peter; Al‐Harrasi, Ahmed; Csuk, René

doi:10.3390/molecules26072102

Cited by 14 publications

(14 citation statements)

References 44 publications

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“…Acetylation of GA (Scheme 1) gave 1 in 91% 50 whose activation by oxalylchloride in the presence of a catalytic amount of dimethylformamide (DMF) followed by the addition of either ethylenediamine, piperazine, homopiperazine, morpholine, thiomorpholine, homomorpholine, homothiomorpholine, 1,4-diazabicyclo[3.2.2] nonane 24 , 1,3-diazabicyclo[3.2.2]nonane 24,51 gave amides 2-10; reaction of 9 and 10 with methyl iodide resulted in the formation of the quaternary ammonium iodides 11 and 12, respectively. For comparison, primary amide 13 was prepared, and the Curtius degradation 52,53 of 1 gave amine 14.…”

Section: Resultsmentioning

confidence: 99%

“…in the past to be cytotoxic 11,18,19,[21][22][23][24]26,33,34,[37][38][39] , and of special interest are those holding a heterocyclic ring at the distal amide position. Consequently, we became interested in the synthesis of 3-O-acetylated glycyrrhetinic acid amides holding heterocyclic moieties differing in the kind of heteroatoms (N, O, S), ring size (acyclic, 6, 7), and the steric demand of the heterocyclic system.…”

Section: Amides Of Triterpene Carboxylic Acids Have Been Shownmentioning

confidence: 99%

“…While there have been numerous studies on the cytotoxic activity of triterpene carboxylic acids such as oleanolic [22][23][24][25][26] , ursolic [27][28][29][30][31][32] , maslinic 33-40, or betulinic acid [41][42][43][44][45][46][47][48][49] , the number of publications on glycyrrhetinic acid derivatives is incomparably smaller. This is all the more surprising as this triterpene carboxylic acid is very readily available even in large quantities from a renewable source and hence an ideal starting material for syntheses.…”

Section: Introductionmentioning

confidence: 99%

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Glycyrrhetinic amides and their cytotoxicity

et al. 2021

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3-<em>O</em>-Acetyl-glycyrrhetinic amides were prepared, and sulforhodamine B assays investigated their cytotoxicity. Their cytotoxicity strongly depended on the substitution pattern of the respective compounds. Thereby, an ethylenediamine-derived compound <strong>2</strong> performed the best, acting mainly by apoptosis. As far as heterocyclic amides are concerned, ring enlargement and the replacement of the distal nitrogen invariably led to a more or less complete loss of cytotoxic activity. Thus, the presence of a carbonyl function (C-30) seems necessary for providing significant cytotoxicity.

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Section: Resultsmentioning

confidence: 99%

Section: Amides Of Triterpene Carboxylic Acids Have Been Shownmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glycyrrhetinic amides and their cytotoxicity

et al. 2021

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“…The most active compounds 3a–3c identified in this screening were evaluated for induction of apoptosis in cancer cells. They showed a strong induction of apoptosis in cervical carcinoma and malignant melanoma cells after 24 h. The compounds 3a–4c are novel compounds (as far as the literature data were consulted [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]) in which structural modifications resulted in modification of the biological effects of their parent components (adaptogens). Amides 3a–4c display cytotoxicity and antiproliferative activity, and cause cell apoptosis in human cervical carcinoma (HeLa) and human malignant melanoma (G-361) cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, several review papers have been published in pentacyclic triterpenoids and their structural modifications, including those resulting in the investigation of novel nitrogen-containing compounds [ 28 , 29 , 30 , 31 , 32 ]. However, neither of those review articles [ 28 , 29 , 30 , 31 , 32 ], nor any of the recent research papers [ 33 , 34 , 35 ] have dealt with tryptamine or fluorotryptamine derivatives of oleanolic acid that are the topic of this article as newly designed compounds.…”

Section: Introductionmentioning

confidence: 99%

Novel Oleanolic Acid-Tryptamine and -Fluorotryptamine Amides: From Adaptogens to Agents Targeting In Vitro Cell Apoptosis

Bildziukevich

Kvasnicová

Šaman

et al. 2021

Plants

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Background: Oleanolic acid is a natural plant adaptogen, and tryptamine is a natural psychoactive drug. To compare their effects of with the effect of their derivatives, tryptamine and fluorotryptamine amides of oleanolic acid were designed and synthesized. Methods: The target amides were investigated for their pharmacological effect, and basic supramolecular self-assembly characteristics. Four human cancer cell lines were involved in the screening tests performed by standard methods. Results: The ability to display cytotoxicity and to cause selective cell apoptosis in human cervical carcinoma and in human malignant melanoma was seen with the three most active compounds of the prepared series of compounds. Tryptamine amide of (3β)-3-(acetyloxy)olean-12-en-28-oic acid (3a) exhibited cytotoxicity in HeLa cancer cell lines (IC50 = 8.7 ± 0.4 µM) and in G-361 cancer cell lines (IC50 = 9.0 ± 0.4 µM). Fluorotryptamine amides of (3β)-3-(acetyloxy)olean-12-en-28-oic acid (compounds 3b and 3c) showed cytotoxicity in the HeLa cancer cell line (IC50 = 6.7 ± 0.4 µM and 12.2 ± 4.7 µM, respectively). The fluorotryptamine amide of oleanolic acid (compound 4c) displayed cytotoxicity in the MCF7 cancer cell line (IC50 = 13.5 ± 3.3 µM). Based on the preliminary UV spectra measured in methanol/water mixtures, the compounds 3a–3c were also found to self-assemble into supramolecular systems. Conclusions: An effect of the fluorine atom present in the molecules on self-assembly was observed with 3b. Enhanced cytotoxicity has been achieved in 3a–4c in comparison with the effect of the parent oleanolic acid (1) and tryptamine. The compounds 3a–3c showed a strong induction of apoptosis in HeLa and G-361 cells after 24 h.

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Platanic acid derived amides are more cytotoxic than their corresponding oximes

et al. 2022

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Albeit platanic acid has been known since 1956, its potential to act as a valuable starting material for the synthesis of cytotoxic agents has been neglected for many years. Hereby we describe the synthesis of a small library of amides and oximes derived from 3-O-acetyl-platanic acid, and the results of their screening as cytotoxic agents for several human tumor cell lines. As a result, while the cytotoxicity of the oximes was diminished as compared to the parent amides, the homopiperazinyl amide 5 held the highest cytoxicity (EC50 = 0.9 μM for A375 human melanoma cells). Extra FACS and cell cycle measurements showed compound 5 to act onto A375 cells rather by apoptosis than by necrosis. Clinical trial registration No clinical trials are associated with this study

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The Presence of a Cyclohexyldiamine Moiety Confers Cytotoxicity to Pentacyclic Triterpenoids

Cited by 14 publications

References 44 publications

Glycyrrhetinic amides and their cytotoxicity

Glycyrrhetinic amides and their cytotoxicity

Novel Oleanolic Acid-Tryptamine and -Fluorotryptamine Amides: From Adaptogens to Agents Targeting In Vitro Cell Apoptosis

Platanic acid derived amides are more cytotoxic than their corresponding oximes

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