Thalidomide dithiocarbamate and dithioate derivatives induce apoptosis through inhibition of histone deacetylases and induction of caspases

Zahran, M. A.; Gamal‐Eldeen, Amira M.; El‐Hussieny, Enas A.; Agwa, Hussein S.

doi:10.1016/j.jgeb.2014.03.003

Cited by 7 publications

(15 citation statements)

References 40 publications

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“…The outcome results of phthalimide derivatives 8f, 9e and 9i revealed the superior relative activity of cyclohexylamine and piperidine side chains which supports our previously reported data using the same dithiocarbamate and dithioate moieties with thalidomide [8,11]. Moreover, the introduction of alkyl linker in between phthalimide and dithiocarbamate moieties in derivatives 9e and 9i added a value in improving their biological activities.…”

Section: Assessment Of Phthalimide Derivatives On Vegfr Concentrationsupporting

confidence: 86%

“…Based on these results and assumption, new series of phthalimide derivatives were synthesized and evaluated as potential antitumor drug candidates [6,7]. Recently, our group reported the potency of the thalidomide dithiocarbamate analogs as novel antitumor derivatives [8][9][10][11][12][13][14]. On the other hand, dithiocarbamic acid esters have drawn a great attention due to their cancer chemopreventive and antitumor activities [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, dithiocarbamic acid esters have drawn a great attention due to their cancer chemopreventive and antitumor activities [15,16]. Some molecules that incorporated dithiocarbamic acid ester functionality, as a linker between different pharmacophores, showed significant anticancer activities, such as TH derivatives [8][9][10][11][12][13][14], chromones [17], quinazolinones [18] and naphthalimide derivatives [19].…”

Section: Introductionmentioning

confidence: 99%

“…Our research interest is still existing in development of TH analogs and potential antitumor compounds [8][9][10][11][12][13][14][20][21][22]. So, we herein describe the design, synthesis and biological evaluation of novel dithiocarbamate analogs connected either through methylene or ethylene bridges to phthalimide pharmacophoric core.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and biological evaluation of phthalimide dithiocarbamate and dithioate derivatives as anti-proliferative and anti-angiogenic agents-I

et al. 2017

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A facile synthesis of new phthalimide dithiocarbamate and dithioate analogs 8a-j, 9a-e and 9g-j were achieved by the reaction of N-chloromethyl and N-bromoethylphthalimide with carbon disulfide (CS2) and various amines. The structures of the synthesized analogs were elucidated by spectroscopic methods, including IR, 1 H NMR and 13 C NMR, and ESI-HRMS techniques. The antiproliferative activity of the newly synthesized compounds was also evaluated against various human cancer cell lines. The compound 9e and 9i exhibited the highest activity against human breast adenocarcinoma MCF-7 and hepatocellular carcinoma HepG2 cells. Compound 8f showed better antiproliferative effect against colon carcinoma HCT-116 and cervical carcinoma HeLa compared to thalidomide. The binding affinity to vascular endothelial growth factor receptor (VEGFR) of some compounds was assessed in addition to molecular docking study. Compounds 9e and 9i showed high docking score values and they significantly declined the concentration of VEGFR. KEYWORDS

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Section: Assessment Of Phthalimide Derivatives On Vegfr Concentrationsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and biological evaluation of phthalimide dithiocarbamate and dithioate derivatives as anti-proliferative and anti-angiogenic agents-I

et al. 2017

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“…In this regard, a previous study showed that thalidomide and its analogs induced apoptosis and exerted cytotoxic effects on the Hep-G2 and MCF-7 cell lines (17). Another study reported the anti-tumor activities of thalidomide analogs against the HCT-116 and Hep-G2 cell lines (18).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Anti-proliferative Effects of Lenalidomide and Dexamethasone on the HT-29 Cell Line Through Apoptotic Genes

et al. 2021

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Background: Colorectal cancer (CRC) is the third most common cancer among men and the second most common type of cancer among women worldwide. The resistance of tumor cells to apoptosis is caused by changes in the expression of anti-apoptotic or pro-apoptotic proteins. Histone deacetylase inhibitors (HDACi) are known to cause changes in gene expression. Objectives: The present study aimed at investigating the anti-proliferative effects of lenalidomide (LEN) as HDACi and dexamethasone (DEX) on the human colon cancer HT-29 cell line. Methods: The HT-29 cell line was treated with various concentrations of LEN and DEX individually and in combination for 24, 48, and 72 hours. Cytotoxicity was evaluated by MTT assay. The half-maximal inhibitory concentration (IC50) was measured, and quantitative real-time polymerase chain reaction (qRT-PCR) was also performed to examine the expression of Bcl-2, Bax, Fas, and FasL genes. Results: The combination of LEN (1000 µM) with DEX (100 µM) showed potent synergistic anti-proliferative activities in a time- and dose-dependent manner. The combination of these drugs induced cell death by affecting the extrinsic and intrinsic apoptotic gene expression profiles. Conclusions: The combination of LEN with DEX can be proposed as a new therapeutic approach for CRC.

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Synthesis and Evaluation of Thalidomide and Phthalimide Esters as Antitumor Agents

Zahran

Abdin

Osman

et al. 2014

Archiv der Pharmazie

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A series of thalidomide and phthalimide ester analogs were efficiently synthesized from N-chloromethylthalidomide, N-chloromethylphthalimide, and N-(2-bromoethyl)phthalimide derivatives with various biologically important carboxylic acids. The synthesized compounds were purified and characterized by various chromatographic and spectroscopic techniques. The antitumor activity of all the synthesized compounds was screened against human liver and breast cancer cells, which showed that phthalimide ester 6a was the best cytotoxic compound against MCF7 cells, while all of the tested compounds showed a non-cytotoxic effect against HepG2 cells. Compounds 5a, 6a, and 7a possess immunosuppressant effect, while compounds 5c, 5d, 6c, 6d, 7c, and 7d showed an immunostimmulatory effect. Meanwhile, estimation of the binding affinity for all the synthesized compounds toward the vascular endothelial growth factor receptor (VEGFR) showed that compounds 5a, 5b, and 7d were the most potent inhibitors.

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Thalidomide dithiocarbamate and dithioate derivatives induce apoptosis through inhibition of histone deacetylases and induction of caspases

Cited by 7 publications

References 40 publications

Synthesis and biological evaluation of phthalimide dithiocarbamate and dithioate derivatives as anti-proliferative and anti-angiogenic agents-I

Synthesis and biological evaluation of phthalimide dithiocarbamate and dithioate derivatives as anti-proliferative and anti-angiogenic agents-I

Synergistic Anti-proliferative Effects of Lenalidomide and Dexamethasone on the HT-29 Cell Line Through Apoptotic Genes

Synthesis and Evaluation of Thalidomide and Phthalimide Esters as Antitumor Agents

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