Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells

Piven, Yu. A.; Yastrebova, Margarita A.; Khamidullina, Alvina I.; Scherbakov, Alexander M.; Tatarskiy, Victor V.; Rusanova, Julia A.; Baranovsky, A. V.; Zinovich, V. G.; Khlebnicova, Tatyana S.; Лахвич, Ф. А.

doi:10.1016/j.bmc.2021.116521

Cited by 6 publications

(3 citation statements)

References 67 publications

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“…A large number of studies had shown that drugs to promote the apoptosis of cancer cells were one of the main strategies for the treatment of cancer [27,28] . Thus, we further analyzed whether compound 4a 7 could achieve antiproliferation effect by inducing HeLa cells apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…A large number of studies had shown that drugs to promote the apoptosis of cancer cells were one of the main strategies for the treatment of cancer. [27,28] Thus, we further analyzed whether compound 4a 7 could achieve antiproliferation effect by inducing HeLa cells apoptosis. Firstly, to determine the effect of compound 4a 7 on cell apoptosis, the morphological changes of HeLa cells treated with different concentrations of compound 4a 7 were observed using Hoechst 33258 staining assay.…”

Section: Cell Apoptosis Analysismentioning

confidence: 99%

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Design, Synthesis and Anti‐Tumor Activity Evaluation of Novel 3,4‐(Methylenedioxy)cinnamic Acid Amide‐Dithiocarbamate Derivatives

Guo

Cheng

Liu

et al. 2022

Chemistry & Biodiversity

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The fragments, 3,4‐(methylenedioxy)cinnamic acid amide and dithiocarbamates, have received increasing attention because of their multiple pharmacological activities in recent years, especially in anti‐tumor. We synthesized 17 novel 3,4‐(methylenedioxy)cinnamic acid amide‐dithiocarbamate derivatives based on the principle of pharmacophore assembly and discovered that compound 4a7 displayed the most potent antiproliferative activity against HeLa cells with IC50 value of 1.01 μM. Further mechanistic studies revealed that 4a7 triggered apoptosis in HeLa cells via activating mitochondria‐mediated intrinsic pathways and effectively inhibited colony formation. Also, 4a7 had the ability to arrest cell cycle in the G2/M phase as well as to inhibit the migration in HeLa cells. More importantly, acute toxicity experiments showed that 4a7 had good safety in vivo. All the results suggested that compound 4a7 might serve as a promising lead compound that merited further attention in future anti‐tumor drug discovery.

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Section: Resultsmentioning

confidence: 99%

Section: Cell Apoptosis Analysismentioning

confidence: 99%

Design, Synthesis and Anti‐Tumor Activity Evaluation of Novel 3,4‐(Methylenedioxy)cinnamic Acid Amide‐Dithiocarbamate Derivatives

Guo

Cheng

Liu

et al. 2022

Chemistry & Biodiversity

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“…Cell cycle distribution and apoptosis were analyzed as described previously [ 48 ]. MCF7 cells were seeded in 6-well plates in DMEM containing 10% FBS and treated with compounds 3d , 2d , and 1d for 24 h. Сell sediments were lysed in a buffer containing 50 µg/mL propidium iodide (Sigma-Aldrich), 100 µg/mL RNase A (Qiagen), 0.1% sodium citrate, and 0.3% NP-40 (Helicon) for 30 min in the dark at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Novel pentacyclic derivatives and benzylidenes of the progesterone series cause anti-estrogenic and antiproliferative effects and induce apoptosis in breast cancer cells

Scherbakov¹,

Vorontsova

Khamidullina

et al. 2023

Invest New Drugs

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The promising antitumor effects of progesterone derivatives have been identified in many studies. However, the specific mechanism of action of this class of compounds has not been fully described. Therefore, in this study, we investigated the antiproliferative and (anti)estrogenic activities of novel pentacyclic derivatives and benzylidenes of the progesterone series. The antiproliferative effects of the compounds were evaluated on hormone-dependent MCF7 breast cancer cells using the MTT test. Estrogen receptor α (ERα) activity was assessed by a luciferase-based reporter assay. Immunoblotting was used to evaluate the expression of signaling proteins. All benzylidenes demonstrated inhibitory effects with IC 50 values below 10 µM, whereas pentacyclic derivatives were less active. These patterns may be associated with the lability of the geometry of benzylidene molecules, which contributes to an increase in the affinity of interaction with the receptor. The selected compounds showed significant anti-estrogenic potency. Benzylidene 1d ((8 S,9 S,10R,13 S,14 S,17 S)-17-[(2E)-3-(4-fluorophenyl)prop-2-enoyl]-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthren-3-one) was the most active in antiproliferative and anti-estrogenic assays. Apoptosis induced by compound 1d was accompanied by decreases in CDK4, ERα, and Cyclin D1 expression. Compounds 1d and 3d were characterized by high inhibitory potency against resistant breast cancer cells. Apoptosis induced by the leader compounds was confirmed by PARP cleavage and flow cytometry analysis. Compound 3d caused cell arrest in the G2/M phase. Further analysis of novel derivatives of the progesterone series is of great importance for medicinal chemistry, drug design, and oncology. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s10637-023-01332-z.

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Computer-aided design, synthesis and evaluation of new SARS-CoV-2 Mpro inhibitors based on 1,5,6,7-tetrahydro-4H-indazol-4-one scaffold

Piven,

Zinovich,

Shcherbakov

et al. 2023

Med Chem Res

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Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells

Cited by 6 publications

References 67 publications

Design, Synthesis and Anti‐Tumor Activity Evaluation of Novel 3,4‐(Methylenedioxy)cinnamic Acid Amide‐Dithiocarbamate Derivatives

Design, Synthesis and Anti‐Tumor Activity Evaluation of Novel 3,4‐(Methylenedioxy)cinnamic Acid Amide‐Dithiocarbamate Derivatives

Novel pentacyclic derivatives and benzylidenes of the progesterone series cause anti-estrogenic and antiproliferative effects and induce apoptosis in breast cancer cells

Computer-aided design, synthesis and evaluation of new SARS-CoV-2 Mpro inhibitors based on 1,5,6,7-tetrahydro-4H-indazol-4-one scaffold

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