Synthesis and proapoptotic activity of oleanolic acid derived amides

Heller, Lucie; Knorrscheidt, Anja; Flemming, Franziska; Wiemann, Jana; Sommerwerk, Sven; Pavel, Ioana Zinuca; Al‐Harrasi, Ahmed; Csük, René

doi:10.1016/j.bioorg.2016.08.004

Cited by 31 publications

(28 citation statements)

References 31 publications

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“…Jones oxidation 18 of the 3-hydroxyamides 8-12 at 25 °C for 2 hours yielded 3-keto-amides 13-17. These compounds are characterized in their 13 C NMR spectra by the presence of a C = O carbon whose chemical shift was detected between  = 217.2-217.0 ppm, respectively. These amides 13-17 were allowed to react with hydroxylammonium chloride in dry pyridine at 60 °C for 3 hours 7 followed by a precipitation of the crude product by adding 1 M aqueous hydrochloric acid.…”

Section: Resultsmentioning

confidence: 99%

“…(3, 18, 20) 3-Acetoxy-N-benzyl-11-oxoolean-12-en-30-amide (5) As described above, from 2 (2.5 g, 4.88 mmol) and benzylamine (2.0 mL, 18. (3, 18, ) 3-Acetoxy-N-methyl-11-oxoolean-12-en-30-amide (6) As described above, from 2 (4.0 g, 7.81 mmol) and methylamine (12 13  = 3447s, 2942s, 1742s, 1648s, 1627s, 1464m, 1386s, 1124m, 1071w  = 3547m, 3341s, 2974s, 2930s, 2863s, 1659s, 1613m, 1520s, 1455m, 1384m, 1253w, 1205m, 1179m, 1115w, 1081w,  = 3385s, 1954s, 1869s, 1652s, 1541m, 1455s, 1411w, 1384s, 1328w, 1205m, 1091w, 1025w, 13  = 3430s, 2956s, 1660s, 1590s, 1455m, 1383s, 1325s, 1217m, 1130w, 1077w,  = 3306m, 2971s, 1871s, 1695s, 1649s, 1456s, 1387s, 1367w, 1321m, 1261m, 1227m  = 3441s, 2931m, 1727m, 1654s, 1455m, 1386m …”

Section: Methodsmentioning

confidence: 99%

“…The SRB assays were performed as previously reported. 10,13 (18) Glycyrrhetinic acid (1) The starting material for all syntheses was commercially obtained as a bulk chemical from Orgentis GmbH (Gatersleben) and used as received.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and cytotoxicity of 3-amino-glycyrrhetinic acid derivatives

Sahn¹,

Grupe²,

Heller³

et al. 2018

Mediterr.J.Chem.,

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The aim of this study was to prepare 3-hydroximino- and 3-amino derivatives of glycyrrhetinic acid and derivatives to evaluate their in vitro cytotoxicity for a panel of human tumor cell lines. Thus, commercially available glycyrrhetinic acid (1) was acetylated or oxidized at position C-3 and transformed into a variety of different esters and amides followed by their conversion to 3-oximes and amines. While the parent compound was not cytotoxic at all, the 3-amino esters are highly cytotoxic. Interestingly, 3-amino amides were significantly less cytotoxic than 3-amino esters. The (3b, 18b, 20b) Benzyl 3-amino-11-oxoolean-12-en-30-oate was the most cytotoxic compound of this series showing an EC50 = 1.3 mM for 518A2 melanoma cells.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Synthesis and cytotoxicity of 3-amino-glycyrrhetinic acid derivatives

Sahn¹,

Grupe²,

Heller³

et al. 2018

Mediterr.J.Chem.,

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“…To gather more information about the influence of the terpenic part of the molecule on the cytotoxic activity, we prepared four analogous sets of N‐substituted aminothiazoles from four different commercially available triterpenes, allobetulone ( 2 a ), methyl betulonate ( 3 a ), methyl oleanonate ( 4 a ), and oleanonic acid ( 5 a ). Compounds 2 a , 3 a , 4 a , and 5 a are derivatives of triterpenes betulinic acid, oleanolic acid, and 18α‐oleanane; such derivatives are commonly studied for their high cytotoxic activities . Comparing activities in derivatives prepared from methyl oleanonate ( 4 a ) and from free oleanonic acid ( 5 a ) would allow us to estimate, if methyl esters are less active than free acids, as it is usual in triterpenoids …”

Section: Introductionmentioning

confidence: 99%

“…Compounds 2a, 3a, 4a,a nd 5a are derivatives of triterpenes betulinic acid, oleanolic acid, and 18a-oleanane;s uch derivatives are commonly studied for their high cytotoxic activities. [34][35][36][37] Comparing activities in derivatives prepared from methyl oleanonate (4a)a nd from free oleanonic acid (5a) would allow us to estimate, if methyl esters are lessa ctive than free acids, as it is usual in triterpenoids. [20,27,38] The classical Hantzsch synthesis of aminothiazoles does not give good yields in the case of triterpenoids and steroids because of harsh reactionc onditions [39,40] and the reaction does not allow to simply obtain N-substituted compounds.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Cytotoxic Activity of Triterpenoid Thiazoles Derived from Allobetulin, Methyl Betulonate, Methyl Oleanonate, and Oleanonic Acid

et al. 2017

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A total of 41 new triterpenoids were prepared from allobetulone, methyl betulonate, methyl oleanonate, and oleanonic acid to study their influence on cancer cells. Each 3-oxotriterpene was brominated at C2 and substituted with thiocyanate; subsequent cyclization with the appropriate ammonium salts gave N-substituted thiazoles. All compounds were tested for their in vitro cytotoxic activity on eight cancer cell lines and two non-cancer fibroblasts. 2-Bromoallobetulone (2 b) methyl 2-bromobetulonate (3 b), 2-bromooleanonic acid (5 b), and 2-thiocyanooleanonic acid (5 c) were best, with IC values less than 10 μm against CCRF-CEM cells (e.g., 3 b: IC =2.9 μm) as well as 2'-(diethylamino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5 f, IC =9.7 μm) and 2'-(N-methylpiperazino)olean-12(13)-eno[2,3-d]thiazole-28-oic acid (5 k, IC =11.4 μm). Compound 5 c leads to the accumulation of cells in the G phase of the cell cycle and inhibits RNA and DNA synthesis significantly at 1×IC . The G /M cell-cycle arrest probably corresponds to the inhibition of DNA/RNA synthesis, similar to the mechanism of action of actinomycin D. Compound 5 c is new, active, and nontoxic; it is therefore the most promising compound in this series for future drug development. Methyl 2-bromobetulonate (3 b) and methyl 2-thiocyanometulonate (3 c) were found to inhibit nucleic acid synthesis only at 5×IC . We assume that in 3 b and 3 c (unlike in 5 c), DNA/RNA inhibition is a nonspecific event, and an unknown primary cytotoxic target is activated at 1×IC or lower concentration.

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Design, Synthesis and Biological Evaluation of Novel Gypsogenin Derivatives as Potential Anticancer and Antimicrobial Agents

Emirdağ,

Ulusoy,

Aksel

2024

Chemistry & Biodiversity

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Natural compounds are important sources for the treatment of chronic disorders such as cancer and microbial infectious disorders. In this research, Gypsogenin and its derivatives (2a‐2f) have been tested against different cancer cell lines (MCF‐7, HeLa, Jurkat and K562 cell lines) and further analyzed for cell proliferation, cell death type, and for act of the mechanism. Cell proliferation was determined by the MTT method and cell death types were analyzed with HO/PI staining. Fibroblast Growth Factor 1 (FGF‐1), Interleukin 1 (IL‐1), Interleukin 6 (IL‐6), and Tumor Necrosis Factor Alpha (TNF‐α), key players in breast cancer development and progression, were determined by Elisa kits. Results showed that compound 2e inhibited the MCF‐7 cell line proliferation with an IC50 value of 0.66±0.17 µM with 93.38% apoptosis rate. Compound 2e also decreased FGF‐1, IL‐1, IL‐6, and TNF‐α levels. Molecular docking studies performed in the binding site of FGFR‐1 indicated that compound 2e formed key hydrogen bonding with Arg627 and Asn568. Besides, compounds 2a‐2f were evaluated for their antimicrobial activities against gram‐negative and gram‐positive bacteria and C. albicans via the microdilution method. Overall, compound 2e stands out as a potential anticancer agent for future studies.

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Synthesis and proapoptotic activity of oleanolic acid derived amides

Cited by 31 publications

References 31 publications

Synthesis and cytotoxicity of 3-amino-glycyrrhetinic acid derivatives

Synthesis and cytotoxicity of 3-amino-glycyrrhetinic acid derivatives

Synthesis and Cytotoxic Activity of Triterpenoid Thiazoles Derived from Allobetulin, Methyl Betulonate, Methyl Oleanonate, and Oleanonic Acid

Design, Synthesis and Biological Evaluation of Novel Gypsogenin Derivatives as Potential Anticancer and Antimicrobial Agents

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