Design, synthesis and cytotoxicity screening of new synthesized pyrimidine-5-carbonitrile derivatives showing marked apoptotic effect

Zaki, Islam; Masoud, Reham E; Hamoud, Mohamed M.S.; Ali, Ola A. Abu; Abualnaja, Matokah; Fayad, Eman; Almaaty, Ali H. Abu; Elnaghia, Lamis K.

doi:10.1016/j.molstruc.2022.132749

Cited by 13 publications

(8 citation statements)

References 36 publications

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“…MTT assay method was applied to assess cell viability assay. All experimental steps were conducted as reported earlier 14 .…”

Section: Methodsmentioning

confidence: 99%

“…Apoptosis in MDA-MB-231 cells was investigated using a fluorescent Annexin V-FITC/PI detection kit (BioVision Annexin V-FITC Apoptosis Detection Kit, Catalog #: K101) by flow cytometry assay. All experimental steps were conducted as reported earlier 14 .…”

Section: Methodsmentioning

confidence: 99%

“…The levels of the tumour suppressor gene p53, apoptotic markers Bax as well as the anti-apoptotic marker Bcl-2 were assessed using the p53 ELISA kit, Human Bax ELISA kit, and Bcl-2 Elisa kit. The procedure of the used kits was done according to the manufacturer's instructions and was conducted as reported earlier 14 .…”

Section: Methodsmentioning

confidence: 99%

“…Caspase 3/7 activity in the MDA-MB-231 cell line was detected in the presence of compounds 6 and 12 at their IC50 concentration (µM) using CellEvent ® caspase 3/7 green detection flow cytometry assay kit according to the manufacturer’s directions. All experimental steps were conducted as reported earlier 14 .…”

Section: Methodsmentioning

confidence: 99%

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Design and synthesis of new trimethoxylphenyl-linked combretastatin analogues loaded on diamond nanoparticles as a panel for ameliorated solubility and antiproliferative activity

Zaki

Moustafa

Beshay

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new series of vinyl amide-, imidazolone-, and triazinone-linked combretastatin A-4 analogues have been designed and synthesised. These compounds have been evaluated for their cytotoxic activity against MDA-MB-231 breast cancer cells. The triazinone-linked combretastatin analogues (6 and 12) exhibited the most potent cytotoxic activity, in sub-micromolar concentration compared with combretastatin A-4 as a reference standard. The results of β-tubulin polymerisation inhibition assay appear to correlate well with the ability to inhibit β-tubulin polymerisation. Additionally, these compounds were subjected to biological assays relating to cell cycle aspects and apoptosis induction. In addition, the most potent compound 6 was loaded on PEG-PCL modified diamond nanoparticles (PEG-PCL-NDs) and F4 was picked as the optimum formula. F4 exhibited enhanced solubility and release over the drug suspension. In the comparative cytotoxic activity, PEG-PCL modified F4 was capable of diminishing the IC50 by around 2.89 times for nude F4, while by 3.48 times relative to non-formulated compound 6 .

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“…MTT assay method was applied to assess cell viability assay. All experimental steps were conducted as reported earlier 14 .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Design and synthesis of new trimethoxylphenyl-linked combretastatin analogues loaded on diamond nanoparticles as a panel for ameliorated solubility and antiproliferative activity

Zaki

Moustafa

Beshay

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…On the basis of the aforementioned structural analysis, as well as in keeping with our general enthusiasm for the design and development of novel anticancer agents, [29][30][31][32], as potential anticancer medicines, the current work focused on the design and synthesis of novel Schiff bases-based TMP moieties. The basic structural skeleton of the lead compound is formed from two TMP rings connected through amideacrylic acid hydrazide groups.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties

et al. 2022

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A series of novel Schiff bases-based TMP moieties have been designed and synthesized as potential anticancer agents. The target Schiff bases were screened for their cytotoxic activity against the MDA-MB-231 breast cancer cell line. Most of the tested molecules revealed good cytotoxic activity, especially compounds 4h, 4j and 5d. Being the most potent, compound 4h showed good tubulin polymerization inhibition activity as revealed by immunofluorescence analysis and ELISA assay. Additionally, compound 4h was screened for cell cycle disturbance and apoptosis induction. Pre-G1 apoptosis and cell growth halt at the G2/M phase were discovered to be caused by it. Moreover, compound 4h induced apoptosis via p53 and Bax activation, as well as reduced the level of Bcl-2. Additionally, the most potent compound 4h was lodged on nanostructured lipid carriers (NLCs). 23 full factorial design was involved to govern the influence of the fabrication variables on the in vitro characters of the casted NLCs. F3 was picked as the optimum formula exhibiting dominant desirability value 0.805, EE% 95.6 ± 2.4, PS 222.4 ±18.7, PDI 0.23 ± 0.05 and ZP −39.2 ± 3.9 Mv. Furthermore, F3 affirmed improved solubility and release over the drug suspension. In the comparative cytotoxic activity, F3 was capable of diminishing the IC50 by around 2.15 times for pure 4h, while nearly close to the IC50 of the reference drug. Thus, NLCs could be a potential platform for boosted antitumor activity.

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Molecular overlay-guided design of new CDK2 inhibitor thiazepinopurines: Synthesis, anticancer, and mechanistic investigations

Husseiny,

Abulkhair,

Saleh

et al. 2023

Bioorganic Chemistry

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Design, synthesis and cytotoxicity screening of new synthesized pyrimidine-5-carbonitrile derivatives showing marked apoptotic effect

Cited by 13 publications

References 36 publications

Design and synthesis of new trimethoxylphenyl-linked combretastatin analogues loaded on diamond nanoparticles as a panel for ameliorated solubility and antiproliferative activity

Design and synthesis of new trimethoxylphenyl-linked combretastatin analogues loaded on diamond nanoparticles as a panel for ameliorated solubility and antiproliferative activity

Design, Synthesis, In Vitro Biological Activity Evaluation and Stabilized Nanostructured Lipid Carrier Formulation of Newly Synthesized Schiff Bases-Based TMP Moieties

Molecular overlay-guided design of new CDK2 inhibitor thiazepinopurines: Synthesis, anticancer, and mechanistic investigations

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