Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

Mehmood, Hasnain; Musa, Mustapha; Woodward, Simon; Hossan, Shahadat; Bradshaw, Tracey D.; Haroon, Muhammad; Nortcliffe, Andrew; Akhtar, Tashfeen

doi:10.1039/d2ra03226k

Cited by 8 publications

(3 citation statements)

References 38 publications

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“…FLU (for E. coli ) and mexB (for K. pneumoniae ) genes have been chosen to evaluate our thiazoles compounds activity, as these two genes are counted as virulence factors which are required to form biofilm. The library of compounds ( 3 a–m ) (Table 2) was prepared using 3‐bromo‐1,1,1‐trifluoroacetone from a range of readily available thiosemicarbazones ( 1 a–m ) used in our previous studies [8c,11b–d] . Refluxing of reaction components in ethanol for 3–4 hours resulted in good to high yields (73–85 %) of 3 a – m .…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression

Abed,

Abid,

Turki

et al. 2024

ChemistrySelect

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Cyclization of substituted thiosemicarbazones with 3‐bromo‐1,1,1‐trifluoroacetone affords new 2‐(arylidenehydrazinyl)‐4‐trifluoromethylthiazoles (3 a–m, 13 examples, 71–89 %). These compounds were synthesized in two steps and characterized using 1H‐, 13C‐NMR, FTIR spectroscopy, and HRMS. All of these compounds show potent activity against both Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia) bacterial strains. The compounds 2‐(2‐(1‐(4‐fluorophenyl)ethylidene)hydrazinyl)‐4(trifluoromethyl)thiazole (3 b), 2‐(2‐(2‐hydroxy‐3‐methylbenzylidene)hydrazinyl)‐4‐(trifluoromethyl)thiazole (3 c), and 2‐(2‐(3‐fluorobenzylidene)hydrazinyl)‐4‐(trifluoromethyl)thiazole (3 k) show optimal minimum inhibitory concentration (MIC) values of 16 μg/mL against E. coli and (32, 32, and 8 μg/ml) against K. pneumonia, respectively. Using a qRT‐PCR technique the gene expression of two different genes (FLU and mexB) was determined. Most of these compounds (3 a, d–j, l, m) exhibited downregulation of these genes for both types of bacteria, whereas the gene expressions were unaffected after treating 3 b, 3 c and 3 k. This means that although these compounds were able to inhibit bacterial growth, they did not target the FLU and mexB genes in both types of bacteria. These findings suggest further investigations for lead optimization could provide viable antibiotics due to their structural similarity with some commercially available antibiotics.

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Section: Resultsmentioning

confidence: 99%

“…Substituted thiosemicarbazones (0.001 mol) used in our previous studies, [8c,11b–d] were refluxed with equimolar 3‐bromo‐1,1,1‐trifluoroacetone in ethanol (20 mL) for three to four hours. The reaction progress was monitored by TLC ( n ‐hexane:acetone, 3 : 1).…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression

Abed,

Abid,

Turki

et al. 2024

ChemistrySelect

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“…In this context, cell cycle arrest is one of the main mechanisms that are involved in the development of anticancer compounds. The literature data highlighted that antiproliferative TSCs could affect cell cycle progression: some of them can induce G1/S [ 37 , 38 ] or G2/M [ 39 , 40 ] cell cycle block, while other compounds do not cause cell cycle arrest.…”

Section: Introductionmentioning

confidence: 99%

Modulation of Transcription Profile Induced by Antiproliferative Thiosemicarbazone Metal Complexes in U937 Cancer Cells

et al. 2023

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Since the discovery of cisplatin, the search for metal-based compounds with therapeutic potential has been a challenge for the scientific community. In this landscape, thiosemicarbazones and their metal derivatives represent a good starting point for the development of anticancer agents with high selectivity and low toxicity. Here, we focused on the action mechanism of three metal thiosemicarbazones [Ni(tcitr)2], [Pt(tcitr)2], and [Cu(tcitr)2], derived from citronellal. The complexes were already synthesized, characterized, and screened for their antiproliferative activity against different cancer cells and for genotoxic/mutagenic potential. In this work, we deepened the understanding of their molecular action mechanism using an in vitro model of a leukemia cell line (U937) and an approach of transcriptional expression profile analysis. U937 cells showed a significant sensitivity to the tested molecules. To better understand DNA damage induced by our complexes, the modulation of a panel of genes involved in the DNA damage response pathway was evaluated. We analyzed whether our compounds affected cell cycle progression to determine a possible correlation between proliferation inhibition and cell cycle arrest. Our results demonstrate that metal complexes target different cellular processes and could be promising candidates in the design of antiproliferative thiosemicarbazones, although their overall molecular mechanism is still to be understood.

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Synthesis, Molecular Docking, and Anticancer Screening of Ester‐Based Thiazole Derivatives

Musa,

Bello,

Agwamba

2024

Chemistry & Biodiversity

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This study investigates the potential of five compounds as novel anticancer agents. We examined their efficacy, mechanisms of action, and impact on various cancer cell lines, through a comprehensive set of experiments. Notably, compound 3e demonstrated superior activity compared to the positive control cisplatin, with a GI50 value of 6.3±0.7 μM against the breast cancer cell line (MCF‐7). Compound 3b also displayed remarkable growth inhibition, yielding GI50 values of 8.7±0.2 μM (MCF‐7) and 8.9±0.5 μM against the colon cancer cell line (HCT‐116). Cell count experiments further confirmed the potent inhibitory effects of compounds 3e, 3b, and 3c on MCF‐7 and HCT‐116 cell growth. Compound 3e demonstrated a reduction of 55–60 % at GI50 and complete inhibition (100 %) at 2x GI50. Compound 3b exhibited 50–55 % reduction (GI50) and 90–95 % inhibition (2x GI50) in HCT‐116 cells. Compound 3c displayed 75–80 % inhibition (2x GI50) and 35–40 % inhibition (GI50) in HCT‐116 cells. In‐depth mechanistic investigations unveiled valuable insights into the mode of action of compound 3e. The cell‐cycle assay demonstrated G2/M phase arrest, DNA damage, and caspase‐mediated apoptosis in both MCF‐7 and HCT‐116 cells. Caspase activation indicated a significant increase in apoptosis following exposure to compound 3e. Furthermore, compound 3e induced reactive oxygen species (ROS) production, influencing HCT‐116 and MCF‐7 cells differently. Elevated ROS production in HCT‐116 cells and distinct effects in MCF‐7 cells contribute to a deeper understanding of the cytotoxic mechanisms of compound 3e. Overall, these findings highlight the potential of the investigated compounds, particularly compound 3e, as effective inducers of apoptosis in cancer cells. Mechanistic insights into cell cycle arrest, caspase‐mediated apoptosis, and ROS modulation provide a comprehensive understanding of their cytotoxic effects. This study offers significant contribution to the development of promising anticancer agents and their therapeutic applications.

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Design, and synthesis of selectively anticancer 4-cyanophenyl substituted thiazol-2-ylhydrazones

Abstract: Cyclization of substituted thiosemicarbazones with α-bromo-4-cyanoacetophenone allows rapid single-step sustainable syntheses of 4-cyanophenyl-2-hydrazinylthiazoles libraries (30 examples, 66–79%).

Cited by 8 publications

References 38 publications

Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression

Synthesis of Substituted Arylidene Hydrazinyl Trifluoromethyl Thiazole Derivatives and their Antibacterial Studies using different Genes Expression

Modulation of Transcription Profile Induced by Antiproliferative Thiosemicarbazone Metal Complexes in U937 Cancer Cells

Synthesis, Molecular Docking, and Anticancer Screening of Ester‐Based Thiazole Derivatives

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