Novel thiazolidine derivatives as potent selective pro-apoptotic agents

Hafez, Donia E.; Hafez, E.N.; Eddiasty, Islam; Shih, Shou-Ping; Chien, Leng-Chiang; Hong, Yi-Jia; Lin, Hung‐Yu; Keeton, Adam B.; Piazza, Gary A.; Abdel‐Halim, Mohammad; Abadi, Ashraf H.

doi:10.1016/j.bioorg.2021.105143

Cited by 8 publications

(2 citation statements)

References 40 publications

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“…The markers were then assessed using a FACS-Caliburflow cytometer (Beckman Coulter, Taipei, Taiwan) and analyzed using WinMDI software. Markers were assessed using a FACS-Caliburflow cytometer (Beckman Coulter, Taipei, Taiwan) and analyzed using WinMDI 2.8 software [ 49 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

Novel 9-Benzylaminoacridine Derivatives as Dual Inhibitors of Phosphodiesterase 5 and Topoisomerase II for the Treatment of Colon Cancer

et al. 2023

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It has been shown that phosphodiesterase 5 (PDE5) inhibitors have anticancer effects in a variety of malignancies in both in vivo and in vitro experiments. The role of cGMP elevation in colorectal carcinoma (CRC) has been extensively studied. Additionally, DNA topoisomerase II (Topo II) inhibition is a well-established mechanism of action that mediates the effects of several approved anticancer drugs such as doxorubicin and mitoxantrone. Herein, we present 9-benzylaminoacridine derivatives as dual inhibitors of the PDE5 and Topo II enzymes. We synthesized 31 derivatives and evaluated them against PDE5, whereby 22 compounds showed micromolar or sub-micromolar inhibition. The anticancer activity of the compounds was evaluated with the NCI 60-cell line testing. Moreover, the effects of the compounds on HCT-116 colorectal carcinoma (CRC) were extensively studied, and potent compounds against HCT-116 cells were studied for their effects on Topo II, cell cycle progression, and apoptosis. In addition to exhibiting significant growth inhibition against HCT116 cells, compounds 11, 12, and 28 also exhibited the most superior Topo II inhibitory activity and low micromolar PDE5 inhibition and affected cell cycle progression. Knowing that compounds that combat cancer through multiple mechanisms are among the best candidates for effective therapy, we believe that the current class of compounds merits further optimization and investigation to unleash their full therapeutic potential.

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Section: Methodsmentioning

confidence: 99%

Novel 9-Benzylaminoacridine Derivatives as Dual Inhibitors of Phosphodiesterase 5 and Topoisomerase II for the Treatment of Colon Cancer

et al. 2023

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“…Anticancer activity is one of the pharmacological features shown by isatin-thiazole/thiazolidinone derivatives and several anticancer drugs such as tiazofurin and bleomycin have this moiety [25]. This class of compounds have therefore been explored as potential anticancer leads [23,26].…”

Section: Isatin-thiazole/thiazolidinone Derivativesmentioning

confidence: 99%

Effect of Substituents on the Biological Activity of Isatin Hybrids – A SAR Study

Soam¹,

Dasgupta²

2023

ijcsrr

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Isatin (2,3-dioxindole) is a benzopyrrole derivative that belongs to a large class of heterocyclic chemicals. Isatin derivatives are essential synthetic substrates that can be utilized as starting materials to build a wide range of heterocycles with diverse applications in pharmaceutical sciences. Isatin derivatives therefore have recently gained a lot of attention. This review emphasizes on the Schiff base derivatives from isatin, isatin quinoline/flouroquinone, isatin -thiazole, isatin–azole hybrids, all possessing potential biological activity. The structure–activity relationships of these potential leads are also discussed.

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Synthesis, Characterization, Bioactivity Evaluation, and POM/DFT/Docking Analysis of Novel Thiazolidine Derivatives as Potent Anticancer and Antifungal Agents

Majed,

Abdalzahra,

Al‐Hujaj

et al. 2024

ChemistrySelect

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A series of 2,2′‐(1,4‐phenylene)bis(N‐substituted phenylthiazolidine‐4‐amide) derivatives, denoted as (A3–9), were synthesized, and characterized for their potential applications against prostate cancer cells (PC3), and Candida albicans fungi. These compounds incorporate various substituents on the phenyl ring such as 4‐NO2, 3‐NO2, 4‐COCH3, 4‐H, 4‐OCH3, 4‐OCH2CH3, and 4‐Cl. The chemical structures of these derivatives were confirmed by NMR, FTIR, and mass spectroscopy. Biological assays, utilizing the MTT assay for prostate cancer cells (PC3) and the disk diffusion assay for Candida albicans fungi, were conducted to evaluate the bioactivity of these compounds. The results revealed promising cytotoxic and antifungal activities. Specifically, compounds A3 (IC50=69.74±0.96), A4 (IC50=63.64±0.950), and A9 (IC50=57.14±0.88 μg/mL) exhibited notable potency against PC3 cells, while A7 and A8 exhibited considerable antifungal efficacy against Candida albicans with MIC of 312 μg/mL. Moreover, density functional theory (DFT) simulations were used to study electronic properties and reactivity descriptors such as energy gap (Eg), ionization potential (IP), electron affinity (EA), chemical potential (μ), chemical hardness (η), global softness (σ), electronegativity (χ), and electrophilicity (ω) to gain a better understanding of the Structure‐Activity Relationship (SAR). Molecular docking analysis against DNA Gyrase and EGFR tyrosine kinase enzymes revealed strong binding interactions of the investigated molecules within their active sites, making them valuable candidates for further development as therapeutic agents against prostate cancer and fungal infections. POM analysis indicates the presence of two antifungal pharmacophore sites (O1δ−, O2δ−) and (O3δ−, O4δ−), as well as two antitumor pharmacophore sites (O1δ−, NH1δ+) and (O4δ−, NH2δ+).

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Novel thiazolidine derivatives as potent selective pro-apoptotic agents

Cited by 8 publications

References 40 publications

Novel 9-Benzylaminoacridine Derivatives as Dual Inhibitors of Phosphodiesterase 5 and Topoisomerase II for the Treatment of Colon Cancer

Novel 9-Benzylaminoacridine Derivatives as Dual Inhibitors of Phosphodiesterase 5 and Topoisomerase II for the Treatment of Colon Cancer

Effect of Substituents on the Biological Activity of Isatin Hybrids – A SAR Study

Synthesis, Characterization, Bioactivity Evaluation, and POM/DFT/Docking Analysis of Novel Thiazolidine Derivatives as Potent Anticancer and Antifungal Agents

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