The new esters derivatives of betulin and betulinic acid in epidermoid squamous carcinoma treatment – In vitro studies

Drąg-Zalesińska, Małgorzata; Wysocka, Teresa; Borska, Sylwia; Drąg, Marcin; Poręba, Marcin; Choromańska, Anna; Kulbacka, Julita; Saczko, Jolanta

doi:10.1016/j.biopha.2015.04.003

Cited by 29 publications

(30 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After incubation with betulin, the lowest number of apoptotic nuclei were noted (Table 3). In other studies, we examined the cytotoxicity and ability of these derivatives to induce apoptosis in skin cancer cells (A431) and normal keratinocytes (HaCaT) [10]. Our investigation suggested that selected derivatives of betulin can be also useful in the treatment of melanoma cells.…”

Section: Resultsmentioning

confidence: 99%

“…1. Synthesis of these compounds was described in our previous study by Drag-Zalesińska et al [10]. The experimental conditions were based on our previous reports.…”

Section: Methodsmentioning

confidence: 99%

“…The experimental conditions were based on our previous reports. For our studies, we used five selected betulin ester derivatives: four basic amino acids—natural lysine ( l- Lys-OH) and three of its derivatives ( l- Dap-OH, l- Dab-OH, and l- Orn-OH)—and alanine ( l- Ala-OH) as a negative control (amino acid without amine group in side chain) [10], as well as betulin and betulinic acid. The derivatives had increased solubility in water compared to their precursors, which was described in our earlier studies [9].…”

Section: Methodsmentioning

confidence: 99%

“…This result was expected because Ala is hydrophobic and does not have an amino group in the side chain, which influences the biological properties of tested derivatives. Based on our previous studies [10], 6 and 12.5 µM were selected as the concentrations of all compounds for further investigation.

Fig. 1Structures of betulin derivatives: a structure of amino acids used for the synthesis of betulin derivatives used for the treatment of melanoma cells (Me-45); b the general structure of the 5-element collection containing l -amino acids …”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45)

Drąg-Zalesińska¹,

Drąg²,

Poręba³

et al. 2017

Cancer Cell Int

Self Cite

View full text Add to dashboard Cite

BackgroundBetulinic acid and betulin are triterpenes that have anticancer properties in various types of cancer. Unfortunately, the bioavailability and the bio-distribution of betulinic acid and its metabolic precursor, betulin are very low because of poor solubility in aqueous buffers.MethodsIn this study, we examined the anticancer properties of the ester derivatives of betulin compared to their precursors in a malignant melanoma cell line. We assessed five amino acid esters of betulin. The compounds contained four basic amino acids—natural lysine (l-Lys-OH) and three of its derivatives (l-Dap-OH, l-Dab-OH, and l-Orn-OH)—and alanine (l-Ala-OH) as a negative control (amino acid without an amine group in the side chain). The derivatives were more soluble than their precursors (betulin and betulinic acid) in water. The betulin esters were tested in the malignant melanoma cell line Me-45. To evaluate the cytotoxicity, MTT test was performed after 24, 48 and 72 h of incubation with the test compounds at a concentration range of 0.75–100 μM. For analysis of the apoptotic activity, TUNEL assay was performed. Additionally, expression of caspase-3 and PARP-1 was investigated immunocytochemically.ResultsThe highest biological activity was observed with the lysine ester. The results showed that the highest cytotoxicity and the highest number of positively stained nuclei in metastatic melanoma Me-45 cells were obtained after 72 h of incubation with betulin derivatives containing lysine and ornithine.ConclusionsThe betulin ester derivatives showed enhanced antitumor activity compared to their non-modified precursors. Esters of betulin can be more potent anticancer agents than their precursor as a consequence of the rapid bioavailability and increased concentration in cancer cells.

show abstract

Section: Resultsmentioning

confidence: 99%

“…1. Synthesis of these compounds was described in our previous study by Drag-Zalesińska et al [10]. The experimental conditions were based on our previous reports.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45)

Drąg-Zalesińska¹,

Drąg²,

Poręba³

et al. 2017

Cancer Cell Int

Self Cite

View full text Add to dashboard Cite

show abstract

“…antibacterial, antiviral, anti-parasite BE: [5,6]; BA: [7][8][9]; BE/BA: [10,11]; BE/BA/OA: [12]; LU/BA: [13]; OA/BA: [14] hepatoprotective BE: [15]; BE/BA: [16]; OA: [17][18][19][20]; LU: [21]; BA: [22] antitumor BE: [23,24]; BA: [25,26] BE/BA: [27,28]; LU: [29]; OA: [18,19,30] wound healing extract: [31][32][33]; BA: [34]; OA: [35,36] anti-inflammatory BE: [5,37]; LU: [38,39]; OA: [18,40] Apart from these pharmacological effects, birch bark extract is able to act as a gelling agent and Pickering emulsifier [41][42][43]. Together with its anti-inflammatory and wound healing effects, this makes birch bark dry extract interesting for the stabilisation of semisolid systems, such as gels and creams, acting as an active ingredient and an excipient in parallel.…”

Section: Pharmacological Effects Of Triterpenoids Contained In Birch mentioning

confidence: 99%

Birch Bark Dry Extract by Supercritical Fluid Technology: Extract Characterisation and Use for Stabilisation of Semisolid Systems

Armbruster

Mönckedieck²,

Scherließ³

et al. 2017

Applied Sciences

View full text Add to dashboard Cite

Abstract:Triterpene compounds like betulin, betulinic acid, erythrodiol, oleanolic acid and lupeol are known for many pharmacological effects. All these substances are found in the outer bark of birch. Apart from its pharmacological effects, birch bark extract can be used to stabilise semisolid systems. Normally, birch bark extract is produced for this purpose by extraction with organic solvents. Employing supercritical fluid technology, our aim was to develop a birch bark dry extract suitable for stabilisation of lipophilic gels with improved properties while avoiding the use of toxic solvents. With supercritical carbon dioxide, three different particle formation methods from supercritical solutions have been tested. First, particle deposition was performed from a supercritical solution in an expansion chamber. Second, the Rapid Expansion of Supercritical Solutions (RESS) method was used for particle generation. Third, a modified RESS-procedure, forming the particles directly into the thereby gelated liquid, was developed. All three methods gave yields from 1% to 5.8%, depending on the techniques employed. The triterpene composition of the three extracts was comparable: all three gave more stable oleogels compared to the use of an extract obtained by organic solvent extraction. Characterizing the rheological behaviour of these gels, a faster gelling effect was seen together with a lower concentration of the extract required for the gel formation with the supercritical fluid (SCF)-extracts. This confirms the superiority of the supercritical fluid produced extracts with regard to the oleogel forming properties.

show abstract

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

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

The new esters derivatives of betulin and betulinic acid in epidermoid squamous carcinoma treatment – In vitro studies

Cited by 29 publications

References 29 publications

Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45)

Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45)

Birch Bark Dry Extract by Supercritical Fluid Technology: Extract Characterisation and Use for Stabilisation of Semisolid Systems

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

Contact Info

Product

Resources

About