Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines

Živković, Marijana; Matić, Ivana Z.; Rodić, Marko V.; Novaković, Irena; Sladić, Dušan; Krstić, Natalija M.

doi:10.1039/c6ra01516f

Cited by 17 publications

(30 citation statements)

References 69 publications

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“…Additionally, these compounds showed a strong anti-angiogenic acitivity. The results from our research also, suggest that α,β-unsaturated thiosemicarbazone moiety at C-3 as well as the spiro heterocyclic substituent at C-17 position enhanced the activity of investigated compounds [3].…”

Section: Introductionsupporting

confidence: 70%

“…3-Thiosemicarbazones and 3,17-bis(thiadiazolines) exhibited the best activity against all cancer cell lines used in this work [3]. The study of the mechanisms of anticancer activity revealed that these compounds induced apoptosis in HeLa cells, through extrinsic and intrinsic signalling pathways [3]. Additionally, these compounds showed a strong anti-angiogenic acitivity.…”

Section: Introductionmentioning

confidence: 90%

“…Recently we reported synthesis of new steroidal mono-and bis(thiosemicarbazones) and mono-and bis(1,3,4-thiadiazolines) obtained from several androstene derivatives 1a-f ( Fig. 1) and their cytotoxic activity in vitro [3]. Mono-and bis(thiosemicarbazones) were found to be a mixtures of (E)-and (Z)-isomers differing in configuration on the C(3)=N1 double bond.…”

Section: Introductionmentioning

confidence: 99%

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Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro

Živković

Matić

Rodić

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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The synthesis and cytotoxic activities determination of new steroidal mono- and bis(thiazolidin-4-ones) 4a-f and 5a-f have been performed. Their anticancer action was also evaluated in comparison to previously synthesized and reported corresponding steroidal thiosemicarbazones. All compounds were obtained as stereoisomeric mixtures with different configuration (E or Z) in the hydrazone moiety at the C-3 position. After several consecutive crystallizations diastereomerically pure major (E)-isomers of mono-thiazolidin-4-ones were isolated. The structure and stereochemistry of 2,4-thiazolidinedione,2-[(17-oxoandrost-4-en-3-ylidene)hydrazone] were confirmed by X-ray analysis. A pathway for the formation of thiazolidin-4-one ring was proposed. The steroid thiazolidinone derivatives examined in this study exerted selective concentration-dependent cytotoxic activities on six tested malignant cell lines. Ten out of twelve examined compounds exhibited strong cytotoxic effects on K562 cells (IC values from 8.5μM to 14.9μM), eight on HeLa cells (IC values ranging from 8.9μM to 15.1μM) while against MDA-MB-361 cells six compouds exerted similar or even higher cytotoxic action (IC values from 12.7μM to 25.6μM) than cisplatin (21.5μM) which served as a positive control. Eight of these ten compounds showed high selectivity in the cytotoxic action against HeLa and K562 cancer cell lines when compared with normal human fibroblasts MRC-5 and normal human PBMC. The study of mechanisms of the anticancer activity of the two selected compounds, mono- and bis(thiazolidin-4-one) derivatives of 19-norandrost-4-ene-3,17-dione 4a and 5a, revealed that both of these compounds induced apoptosis in HeLa cells through extrinsic and intrinsic signalling pathways. Treatment of EA.hy926 cells with sub-toxic concentrations of these compounds led to the inhibition of cell connecting and sprouting, and tube formation. The synthesized compounds exhibited poor antioxidant activity.

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Section: Introductionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

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Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro

Živković

Matić

Rodić

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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“…The next day, the extracts and cisplatin, as a positive control, were added to cells at 2IC50 concentrations. After 24 hours of incubation, the cells were stained with a mixture of acridine orange and ethidium bromide dyes (3 μg/mL acridine orange and 10 μg/mL ethidium bromide in phosphate buffered saline (PBS), and visualized under a fluorescence microscope -Carl Zeiss PALM MicroBeam with Axio Observer.Z1 using AxioCam MRm (filters Alexa 488 and 568), as already described (Matić et al, 2013a;Živković et al, 2016).…”

Section: Morphological Evaluation Of Cell Deathmentioning

confidence: 99%

“…The assay was described elsewhere (Aranda and Owen, 2009;Matić et al, 2013a;Živković et al, 2016). Plates were incubated for 2 hours.…”

Section: Tube Formation Assaymentioning

confidence: 99%

Evaluation of the anti-cancer potential of Mahonia aquifolium extracts via apoptosis and anti-angiogenesis

Damjanović

Zdunić²,

Šavikin³

et al. 2016

Bangladesh J Pharmacol

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The cytotoxicity of Mahonia aquifolium ethanol and water extracts was examined using MTT test. The morphological changes were analyzed by fluorescence microscopy. Cell cycle distribution and possible activation of caspase-dependent pathway of cell death were assessed by flow cytometry. The effects of ethanol and water extracts on migration of endothelial EA.hy926 cells were analyzed by in vitro scratch assay and inhibition of angiogenesis was detected using tube formation assay. Both extracts demonstrated cytotoxic effects on cancer cell lines with very high selectivity. Morphological evaluation indicated apoptosis. These results were confirmed with cell cycle analysis, where there was accumulation of cancer cells in the subG1 phase. Ethanol and water extracts induced a caspase-dependent apoptosis in HeLa cells through activation of caspase-3 and caspase-8. Both extracts showed the ability to inbibit the migration of EA.hy926 cells and initial steps of angiogenesis. In addition, ethanol extract exerted significant anti-angiogenic effect.Video Clip:<a href="https://www.youtube.com/v/_b1LobagxyA">Cell seeding</a>: 2 min 26 sec<a href="https://www.youtube.com/v/LZrwdyvFAyI">4 hours after treatment of MTT-SDS applied</a>: 54 sec<a href="https://www.youtube.com/v/a6Dshdsg8TY">72 hours after treatment MTT applied</a>: 1 min 8 sec<a href="https://www.youtube.com/v/RE_SH-CauRU">Day 2 treatment</a>: 1 min 32 sec<a href="https://www.youtube.com/v/l4E1y0lgrAE">Measuring absorbance</a>: 9 sec

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Microwave‐assisted synthesis and antimicrobial activity of novel spiro 1,3,4‐thiadiazolines from isatin derivatives

Costa

Castro

Silva

et al. 2020

Journal of Heterocyclic Chem

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This work describes the synthesis of spiro 1,3,4‐thiadiazolines from isatin‐β‐thiosemicarbazone acetylation, using microwave irradiation as a source of heating the reaction medium. N‐substituted isatin derivatives were used as substrates to obtain thiosemicarbazones by adding thiosemicarbazide to the isatin ketone carbonyl. The final synthetic step was the reaction of thiosemicarbazones with acetic anhydride under microwave irradiation to get the spiro compounds. Reaction times ranged from 6 to 18 minutes resulting in yields of up to 90%. Biological assays have shown promising antibacterial and antifungal activity, especially spiro thiadiazolines derived from allylated isatins. All the proposed molecules proved to be potential drug candidates based on the results of the in silico investigation, with satisfactory drug‐likeness and drug‐score, respecting Lipinski's rule. The use of the microwave reactor was efficient for the synthesis of thiosemicarbazones and spiro compounds, resulting in a significant reduction in reaction times with conventional heating. Taking into account the threat of antimicrobial resistance, this work presents a series of bioactive molecules that are easily obtained via microwave reaction.

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Synthesis, characterization and in vitro cytotoxic activities of new steroidal thiosemicarbazones and thiadiazolines

Abstract: New steroidal thiosemicarbazones and 1,3,4-thiadiazolines as potential anticancer agents are described.

Cited by 17 publications

References 69 publications

Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro

Anticancer potential of new steroidal thiazolidin-4-one derivatives. Mechanisms of cytotoxic action and effects on angiogenesis in vitro

Evaluation of the anti-cancer potential of <i>Mahonia aquifolium</i> extracts via apoptosis and anti-angiogenesis

Microwave‐assisted synthesis and antimicrobial activity of novel spiro 1,3,4‐thiadiazolines from isatin derivatives

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