A novel series of pyrazole-platinum(II) complexes as potential anti-cancer agents that induce cell cycle arrest and apoptosis in breast cancer cells

Abstract

Six novel compounds of platinum(II) with pyrazole derivatives PtPz1–PtPz6 were synthesised and characterised (PtPz1 - [Pt2N-hydroksymethyl-3,5-dimethylpyrazole4(berenil)2]Cl4; PtPz2 - [Pt23,5-dimethylpyrazole4(berenil)2]Cl4; PtPz3 - [Pt23,4-dimethylpyrazole4(berenil)2]Cl4; PtPz4 - [Pt2pyrazole4(berenil)2]Cl4; PtPz5- [Pt25-methylpyrazole4(berenil)2]Cl4; PtPz6 - [Pt2N-ethylpyrazole4(berenil)2]Cl4). The cytotoxic activity of these complexes against MCF-7 and MDA-MB-231 breast cancer cell lines was determined using the MTT assay. Evaluation of apoptosis induction was done with the Annexin V-fluorescein isothiocyanate/propidium iodide assay. In addition, using a flow cytometer, we determined the influence of test compounds on the cell cycle and caspase-3, -8, and -9 activity. The obtained results of caspase activity were confirmed by cell imaging. Moreover, using the flow cytometer, the effects of the test compounds on mitochondrial potential change were assessed. The test results showed that novel pyrazole-platinum(II) complexes exhibited stronger anti-proliferative activity against two breast cancer cell lines than reference cisplatin. Compounds PtPz1, PtPz2, and PtPz3 with methyl substituents at the pyrazole ring showed stronger activity than pyrazole or ethylpyrazole containing complexes. Studies have shown that inhibition of cell survival occurs by arresting the G1 cell cycle and inducing apoptosis. Our analysis associated with the response of MCF-7 and MDA-MB-231 cells to treatment with PtPz1–PtPz6 showed that it leads the cells through the external and intrinsic (mitochondrial) apoptotic pathway via indirect DNA damage.

Benefits and applications of microwave-assisted synthesis of nitrogen containing heterocycles in medicinal chemistry

“…Microwave irradiation was conducted at 5-10 W and 100 C 64 against MCF-7 and MDA-MB-231 breast cancer cell lines. 73 The cytotoxicity has been evaluated toward colon carcinoma HCT116 and leukemia K562 cultured human tumor cells. 74 Other pyrazole drugs with biological activities are Rimonabant, which functions as a cannabinoid receptor and is utilized to treat obesity, Celecoxib, which inhibits COX-2, Fomepizole, an alcohol dehydrogenase inhibitor and Sildenal, which selectively inhibits phosphodiesterase type 5.…”

Transcriptome-based Stemness Indices Analysis Reveals Platinum-based Chemotheraputic Response Indicators in Advanced-stage Serous Ovarian Cancer

“…Interestingly, the selected key genes were also enriched to the platinum response-associated pathways "cellular senescence" [13][14][15], "p53 signaling pathway" [16,17], and "Platinum drug resistance" ( Figure 3B). Cell cycle arrest was also the main molecular mechanism of the platinum anticancer effect [18,19]. To explore the potential predictor of platinum-based therapeutic response, we selected a total of 13 key genes enriched to the four platinum response-associated pathways to be further analyzed in advanced-stage SOC.…”

The Chemistry of Acetylpyrazoles and Its Utility in Heterocyclic Synthesis

“…Several 1‐(1‐aryl‐4‐benzoyl‐1 H ‐pyrazol‐3‐yl)ethanones 18a–d were prepared in one step by reaction of 1‐phenyl‐3‐( N , N ‐dimethylamino)‐propenone ( 17 ) with each of N ‐aryl 2‐oxo‐propanehydrazonoyl chlorides 4a–d in dioxane and in the presence of triethylamine under reflux in 82–88% yields . In another report , 3‐acetyl‐4‐benzoyl‐1‐arylpyrazoles 18a–d were prepared by reaction of the enaminone 17 with the hydrazonyl chloride 4a–d in ethanolic sodium ethoxide solution at room temperature in 75–79% yields (Scheme ).…”