Homopiperazine-rhodamine B adducts of triterpenoic acids are strong mitocans

Wolfram, Ratna Kancana; Fischer, Lucie; Kluge, Ralph; Ströhl, Dieter; Al‐Harrasi, Ahmed; Csuk, René

doi:10.1016/j.ejmech.2018.06.051

Cited by 52 publications

(26 citation statements)

References 42 publications

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“…Extensions in the design of these compounds led to the synthesis of triterpene conjugates with further modifications in the backbone (→ tormentic acid (TA) and euscaphic acid (EA)) as well as to changes in the ring size of the heterocyclic spacer between the backbone of the triterpene and the RhoB moiety (Figure 8). The significantly higher cytotoxicity (Table 5) of TA-derived 32 seems particularly noteworthy when comparing the different spacers: Thereby, the presence of a homopiperazinyl spacer [96] (as in 32) proved to be clearly superior to the piperazinyl moiety (as in 31). A similar trend was also noted for EA-derived compounds 29 and 30.…”

Section: Resultsmentioning

confidence: 96%

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

et al. 2020

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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.

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Section: Resultsmentioning

confidence: 96%

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

et al. 2020

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“…To evaluate their in vitro cytotoxicity, all the triterpene-homopiperazinyl-rhodamine derivatives were subjected to RB assays and most of them were highly toxic against numerous human cancer cell lines (A2780, A375, HT29, NiH3T3, MCF7, and SW1736). The ursolic acid-homopiperazinyl-rhodamine derivative (Compound 25 , Table 4 ) was one of the compounds that showed a strong cytotoxicity against the tumor cell lines, while it was less cytotoxic on SW1736 cells [ 164 ]. Kahnt et al synthesized amine-spaced conjugates of UA and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).…”

Section: Chemistry Of Uamentioning

confidence: 99%

Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update

Khwaza

Oyedeji

Aderibigbe

2020

IJMS

132

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Ursolic acid is a pharmacologically active pentacyclic triterpenoid derived from medicinal plants, fruit, and vegetables. The pharmacological activities of ursolic acid have been extensively studied over the past few years and various reports have revealed that ursolic acid has multiple biological activities, which include anti-inflammatory, antioxidant, anti-cancer, etc. In terms of cancer treatment, ursolic acid interacts with a number of molecular targets that play an essential role in many cell signaling pathways. It suppresses transformation, inhibits proliferation, and induces apoptosis of tumor cells. Although ursolic acid has many benefits, its therapeutic applications in clinical medicine are limited by its poor bioavailability and absorption. To overcome such disadvantages, researchers around the globe have designed and developed synthetic ursolic acid derivatives with enhanced therapeutic effects by structurally modifying the parent skeleton of ursolic acid. These structurally modified compounds display enhanced therapeutic effects when compared to ursolic acid. This present review summarizes various synthesized derivatives of ursolic acid with anti-cancer activity which were reported from 2015 to date.

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“…Superior cytotoxicity, however, was found for those triterpenoids holding one or two O-acetyl groups on ring A, an amide spacer at C-28 (preferentially a piperazinyl residue), and a rhodamine B moiety attached to this spacer (Sommerwerk et al 2017). EC 50 values in the low micromolar (Kahnt et al 2018;Wolfram et al 2018aWolfram et al , 2018b and even nano-molar range (Sommerwerk et al 2017) were reported for these conjugates.…”

Section: Introductionmentioning

confidence: 95%

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

et al. 2020

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

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Homopiperazine-rhodamine B adducts of triterpenoic acids are strong mitocans

Cited by 52 publications

References 42 publications

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

Mitocanic Di- and Triterpenoid Rhodamine B Conjugates

Ursolic Acid-Based Derivatives as Potential Anti-Cancer Agents: An Update

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

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