Lupane and 18α-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

Borkova, Lucie; Gurská, Soňa; Džubák, Petr; Buriánová, Renata; Hajdúch, Marián; Šarek, Jan; Popa, Igor; Urban, Milan

doi:10.1016/j.ejmech.2016.05.029

Cited by 20 publications

(29 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2α/β‐bromoallobetulone (2 b) : Epimeric mixture of 2‐bromoallobetulones 2 b was prepared according to the general procedure from allobetulone 2 a (10 g, 22.7 mmol) and CuBr 2 (11.2 g, 50 mmol) in mixture of chloroform (50 mL), ethyl acetate (150 mL) and methanol (20 mL). After standard work up without further purification compound 2 b was obtained as white crystals (11.3 g, 96 %): R f =0.50 (toluene/diethyl ether 20:1); mp: 222–224 °C (hexane/MeOH);

{[α]}_{D}^{20}

=+68 ( c =0.55 in CHCl 3 ); (lit . mp: 216–225 °C;

{[α]}_{D}^{20}

=+74).…”

Section: Methodsmentioning

confidence: 99%

“…Cell lines : Cell lines were chosen and used the same way as in our previous work . All cells (if not indicated otherwise) were purchased from the American Tissue Culture Collection (ATCC).…”

Section: Methodsmentioning

confidence: 99%

“…BrU incorporation analysis (RNA synthesis) : For this analysis, the same procedure of cultivation as previously was used. Cells were cultured and treated as above.…”

Section: Methodsmentioning

confidence: 99%

“…50, 15.42, 16.51, 19.51, 21.45, 21.98, 24.55, 26.22, 26.44, 28.79, 30.28, 32.69, 33.03, 34.25, 36.26, 36.71, 37.19, 38.59, 39.28, 40.60, 40.71, 41.48, 46.12, 46.75, 48.07, 49.66, 52.87, 54.27, 71.25, 87.88, 114.97, 147.97, 153.28, 168 49, 15.42, 16.50, 19.44, 21.45, 21.94, 24.54, 24.64, 25.52, 26.21, 26.44, 26.46, 28.80, 30.20, 32. Cell lines:C ell lines were chosen and used the same way as in our previous work. [49,51,54] All cells (if not indicated otherwise) were purchased from the American Tissue Culture Collection (ATCC). The CCRF-CEM line is derived from Tl ymphoblastic leukemia, evincing high chemosensitivity,K 562 represent cells from an acute myeloid leukemia patient sample with Bcr-Abl translocation, U2OS line is derived from osteosarcoma, HCT116 is colorectal tumor cell line and its p53 gene knock-down counterpart (HCT116p53 À/À ,H orizon Discovery Ltd, UK) is am odel of human cancers with p53 mutation frequently associated with poor prognosis, A549 line is lung adenocarcinoma.…”

Section: Methodsmentioning

confidence: 99%

“…These concentrations were used in concordancew ith our previous publications. [49][50][51] Interestingly,h ighly active compound 5c led to the accumulationo fc ells in G 2 phase of the cell cycle and had no toxicity in non-cancerf ibroblasts. Nucleic acid synthesis monitored by BrU/BrDU incorporation was almostc ompletely inhibited by 5c at both tested concentrations, pointing to ap ossible mechanism of action ( Figure 1) somewhere within the regulatory mechanisms of cell-cycle proliferation.…”

Section: Analysis Of Apoptosis Cell Cycle and Dna/rna Synthesismentioning

confidence: 99%

See 4 more Smart Citations

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

et al. 2017

Self Cite

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

{[α]}_{D}^{20}

=+68 ( c =0.55 in CHCl 3 ); (lit . mp: 216–225 °C;

{[α]}_{D}^{20}

=+74).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…BrU incorporation analysis (RNA synthesis) : For this analysis, the same procedure of cultivation as previously was used. Cells were cultured and treated as above.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Analysis Of Apoptosis Cell Cycle and Dna/rna Synthesismentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

Synthesis of Betulinic Acid Derivatives with Modified A‐Rings and their Application as Potential Drug Candidates

2018

View full text Add to dashboard Cite

This Focus Review summarizes recent advances in the synthesis of betulinic acid derivatives with modified A‐rings. It also focuses on their application as potential therapeutic agents for the treatment of cancer and other diseases. Betulinic acid (BA) exhibits therapeutically interesting biological properties, including antitumor, anti‐HIV, antiprotozoal, and hepato‐ or nephroprotective activity; however, its clinical use has been severely limited by its higher IC50 value and worse pharmacological parameters than the currently used drugs. On the other hand, semisynthetic analogues of BA are much better suited for potential clinical use. Among these analogues, compounds that contain a modified A‐ring are the most promising. We hope that this Focus Review will serve as a guide for the synthesis of new BA derivatives with applications as drug candidates. A general audience may also find this Focus Review interesting, because it describes the structural motifs that are responsible for the observed bioactivities.

show abstract

Anticancer 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones as tubulin inhibitors

Řehulka

Subtel’na

Kryshchyshyn‐Dylevych

et al. 2022

Archiv der Pharmazie

Self Cite

View full text Add to dashboard Cite

Studying the anticancer activity of 5-arylidene-2-(4-hydroxyphenyl)aminothiazol-4(5H)-ones towards cell lines of different cancer types allowed the identification of hit-compounds inhibiting the growth of daunorubicin-(CEM-DNR, IC 50 = 0.32-1.28 µM) and paclitaxel-resistant (K562-TAX, IC 50 = 0.21-1.23 µM) cell lines, with favorable therapeutic indexes. The studied compounds induced apoptosis and cellular proliferation in treated CCRF-CEM cells. The hit compounds were shown to induce mitotic arrest by interacting with tubulin, inhibiting its polymerization by binding to the colchicine binding site.

show abstract

Lupane and 18α-oleanane derivatives substituted in the position 2, their cytotoxicity and influence on cancer cells

Cited by 20 publications

References 43 publications

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

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

Synthesis of Betulinic Acid Derivatives with Modified A‐Rings and their Application as Potential Drug Candidates

Anticancer 5‐arylidene‐2‐(4‐hydroxyphenyl)aminothiazol‐4(5H)‐ones as tubulin inhibitors

Contact Info

Product

Resources

About