Synthesis, cytotoxic evaluation, and molecular docking studies of the semi-synthetic “triterpenoid-steroid” hybrids

Толмачева, И. А.; Nazarov, Alexey V.; Ерошенко, Д. В.; Гришко, В. В.

doi:10.1016/j.steroids.2018.10.005

Cited by 20 publications

(12 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other compounds of Stevia pilosa and Stevia eupatoria include β-sitosterol and stigmasterol, which have an antiproliferative effect by activating the extracellular receptor kinase (ERK) 1/2 pathway, and apoptosis induction, decreasing Bcl-2 expression and increasing BAX expression in breast cancer cells MDA-MB-231 [22]. Additionally, some triterpenes demonstrated cytotoxicity in several cells such as colon and stomach cancer cells, inducing apoptosis via extrinsic and intrinsic pathways and activating caspase-8, -9, and -3 [23], and HEp-2, HCT 116, MCF-7, A-549, and PC-3 cancer cells [24]. Fraction compounds, mainly obtained by pinenes, showed a cytotoxic effect in A2058, MCF-7, HL-60, and HeLa cancer cells lines [25].…”

Section: Discussionmentioning

confidence: 99%

Stevia Eupatoria and Stevia Pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells

et al. 2020

View full text Add to dashboard Cite

Background and Objectives: Prostate cancer is the second most harmful disease in men worldwide and the number of cases is increasing. Therefore, new natural agents with anticancer potential should be examined and the response of existing therapeutic drugs must be enhanced. Stevia pilosa and Stevia eupatoria are two species that have been widely used in traditional medicine, but their effectiveness on cancer cells and their interaction with antineoplastic drugs have not been studied. The aim of this study was to evaluate the anticancer activity of Stevia pilosa methanolic root extract (SPME) and Stevia eupatoria methanolic root extract (SEME) and their effect, combined with enzalutamide, on prostate cancer cells. Materials and Methods: The study was conducted on a human fibroblast cell line, and on androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines. The cell viability was evaluated using a Trypan Blue exclusion test for 48 h, and the migration by a wound-healing assay for 24, 48, and 72 h. Results: The results indicate that SPME and SEME were not cytotoxic at concentrations less than 1000 μg/mL in the human fibroblasts. SPME and SEME significantly reduced the viability and migration of prostate cancer cells in all concentrations evaluated. The antiproliferative effect of the Stevia extracts was higher in cancer cells than in normal cells. The enzalutamide decreased the cell viability in all concentrations tested (10–50 µM). The combination of the Stevia extracts and enzalutamide produced a greater effect on the inhibition of the proliferation and migration of cancer cells than the Stevia extracts alone, but not of the enzalutamide alone. Conclusion: The results indicate that SPME and SEME have an inhibitory effect on the viability and migration of prostate cancer cells and do not interfere with the enzalutamide anticancer effect. The data suggest that Stevia extracts may be a potential source of molecules for cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Stevia Eupatoria and Stevia Pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The structures of the previously synthesized derivatives of lupane 3, 5-8 and oleanane 1, 2, 4 types are presented in Figure 1. [18,[20][21][22][23] Advances in the synthesis of triterpenes derivatives with modified A-ring indicated their high potential as therapeutic agents for the treatment of cancer and other diseases. [24] At the same time, despite extensive data on the inhibition of various enzymes by triterpenoids, information on the inhibition of cholinester derivatives with a fragmented ring A is limited.…”

Section: Chemistrymentioning

confidence: 99%

Acetylcholinesterase Inhibitory Activity of Modified Lupane, Oleanane, and Ursane A‐seco‐Triterpenoids

Petrova

Казакова

Назаров

et al. 2023

Chemistry & Biodiversity

View full text Add to dashboard Cite

A series of new lupane, ursane, and oleanane type triterpenic A-seco-derivatives containing bromo-, azido-, alkyne-, 1H-tetrazol-5-yl-, 5-methyloxazol-2-yl-, N-(4-(4-methylpiperazin-1-yl)but-2-yn-1-yl), and a carbonyl group at C2, C24, C28, C30 positions has been synthesized. The bioactivity was evaluated by Ellman's method, and the results showed that most of the compounds displayed moderate acetylcholinesterase inhibitory activities in vitro. Among them, A-seco-derivatives of 28-oxo-allobetuline and betulinic acid with bromo-and azido-groups exhibited the most potent inhibitory activity against AChE. Extra experiments showed methyl 2-cyano-3,4-secodibromo-and 2-cyano-3,4-seco-diazido-derivatives of betulinic acid as mixed-type inhibitors, with Ki values as low as K i = 0.18 μM and K i = 0.21 μM, respectively.

show abstract

“…The molecule of compound 12n could also hydrophobically interact with amino acid residues Ala302, Phe114, Val483, and Val482 (Figure 6b). The pyrizine group played the key role in determining the inhibitory properties of compound 12, because it not only resulted in the formation of the H-bond with Ala302, but also interacted with Ala302 through hydrophobic and van der Waals contacts [34]. The most active compound, 12n, fitted the active sites of CYP17A1 (6CIZ) well.…”

Section: The Molecular Dockingmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Two Series of Novel A-Ring Fused Steroidal Pyrazines as Potential Anticancer Agents

Wang

Yuan

Qian

et al. 2020

IJMS

View full text Add to dashboard Cite

Background: Increasingly, different heterocyclic systems have been introduced into the steroid nucleus to significantly enhance the antitumor activities of steroid molecules. However, in this study, few literature precedents describing the pyrazine heterocyclic-condensed modification to an A-ring of steroid monomers were found, although the pyrazine group is thought to be essential for the potent anticancer activity of clinically relevant drugs and natural steroid dimers. Methods and Results: Two series of novel A-ring fused steroidal pyrazines were designed and efficiently synthesized from commercially available progesterone via key α-ketoenol intermediates. Through a cell counting kit-8 cytotoxic assay of 36 derivatives for three tumor cells, 14 compounds displayed significant antiproliferative activity compared to 5-fluorouracil, especially for human prostatic tumor cells (PC-3) in vitro. Further mechanistic studies indicated that the most active compound, 12n (IC 50 , 0.93 µM; SI, 28.71), could induce the cell apoptosis of PC-3 cells in a dose-dependent manner and cause cell cycle arrest in the G2/M phase. The molecular docking study suggested that compound 12n fitted the active sites of cytochrome P450 17A1 (6CIZ) well. Conclusions: 12n might serve as a promising lead compound for the development of novel anticancer drugs. This facile ring-closing strategy may provide a novel and promising avenue for the cycloaddition reaction of the steroidal skeleton through α-ketoenol intermediates.

show abstract

Synthesis, cytotoxic evaluation, and molecular docking studies of the semi-synthetic “triterpenoid-steroid” hybrids

Cited by 20 publications

References 46 publications

Stevia Eupatoria and Stevia Pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells

Stevia Eupatoria and Stevia Pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells

Acetylcholinesterase Inhibitory Activity of Modified Lupane, Oleanane, and Ursane A‐seco‐Triterpenoids

Design, Synthesis, and Biological Evaluation of Two Series of Novel A-Ring Fused Steroidal Pyrazines as Potential Anticancer Agents

Contact Info

Product

Resources

About