Synthesis, antiproliferative activity, and molecular docking of some <i>N</i>‐heterocycles bearing a pyrazole scaffold against liver and breast tumors

Ramadan, Sayed K.; El‐Ziaty, Ahmed K.; Ali, Rania S.

doi:10.1002/jhet.4168

Cited by 32 publications

(7 citation statements)

References 40 publications

(49 reference statements)

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“…Pyrazoles and their derivatives have attracted particular attention because they have a wide variety of biological activities [2,3], and several drugs currently on the market, have the pyrazole ring as the key structural motif [4]. Some pyrazole derivatives have been demonstrated to be cytotoxic on several human cell lines [5][6][7][8], and, at this time, several drugs that have pyrazoles in their structure have been approved for the treatment of different types of cancer (see Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities

et al. 2021

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Background Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer. Results 4,4ʹ-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4ʹ-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a–q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard. Conclusion Several derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 ± 0.6 µM and exhibited an IC50 of 9.9 ± 1.1 μM against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.

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Section: Introductionmentioning

confidence: 99%

Synthesis of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities

et al. 2021

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“…[ 141 ] Compounds 56 , 57 , and 58 (Figure 12) showed strong cytotoxicity, with IC 50 values in the range of 3.87–10.15 µM against HepG2 and MCF‐7 cell lines. [ 142 ]…”

Section: Biological Activities Of Acrylonitrilesmentioning

confidence: 99%

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Tan

Zengin

2021

Archiv der Pharmazie

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Acrylonitrile is a fascinating scaffold widely found in many natural products, drugs, and drug candidates with various biological activities. Several drug molecules such as entacapone, rilpivirine, teriflunomide, and so forth, bearing an acrylonitrile moiety have been marketed. In this review, diverse synthetic strategies for constructing desired acrylonitriles are discussed, and the different biological activities and medicinal significance of various acrylonitrile derivatives are critically evaluated. The information gathered is expected to provide rational guidance for the development of clinically useful agents from acrylonitriles.

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“…1,4-Benzoxazinone “G” inhibits the coagulation serine proteases factor Xa, thrombin and factor VIIa, and compound “H” possesses a dual antithrombotic action, exhibiting both thrombin inhibitory and fibrinogen receptor antagonistic activities. Apart from benzoxazine derivatives, some other skeletons showed anti-breast cancer activity in the MCF-7 cell line (pyrimidinethione derivatives, pyrrolone derivatives, quinazolinone derivatives, 1,3-diphenylpyrazole derivatives, 1,3-diphenylpyrazolyltetrahydropyrimidine derivatives, Chromone–Pyrazole)…”

Section: Introductionmentioning

confidence: 99%

Tyrosine-Derived Novel Benzoxazine Active in a Rat Syngenic Mammary Tumor Model of Breast Cancer

et al. 2021

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In continuing efforts of improving benzoxazepine derivatives as an anti-breast cancer agent, a new chemical entity, benzoxazine, was designed from scaffold morphing. Structure–activity relationship studies revealed that H, −OMe, −CF3, and −F were well tolerated on R1 and R2 positions of ring A, and R2 as −CH2CH2N(CH2)4 (N-ethyl pyrrolidine) and −CH2CH2N(CH2)5 (N-ethyl piperidine) chains on ring D increased activities (Series B, Figure 3). 13d selected as a lead compound (IC50: 0.20 to 0.65 μM) induces apoptosis, cell cycle arrest, and loss of mitochondrial membrane potential in breast cancer cells. Compound 13d was formulated into 13d–f using cyclodextrin to improve its solubility for a pharmacokinetic, in vivo efficacy study. Both 13d and 13d–f regressed tumor growth at concentrations of 5 and 20 mg/kg better than tamoxifen without any mortality in a rat syngenic mammary tumor model. Collectively, our data suggest that tyrosine-derived novel benzoxazine 13d could be a potential lead for the treatment of breast cancer and hence deserve further in-depth studies.

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Synthesis, antiproliferative activity, and molecular docking of some N‐heterocycles bearing a pyrazole scaffold against liver and breast tumors

Cited by 32 publications

References 40 publications

Synthesis of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities

Synthesis of 4,4′-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Tyrosine-Derived Novel Benzoxazine Active in a Rat Syngenic Mammary Tumor Model of Breast Cancer

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