Design and Synthesis of Chalcone Derivatives as Inhibitors of the Ferredoxin — Ferredoxin-NADP+ Reductase Interaction of Plasmodium falciparum: Pursuing New Antimalarial Agents

Pyrazoline‐linked carboxamide derivatives were designed, synthesized, and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer activity, and apoptotic and cardiomyopathy toxicity. Compounds 6m and 6n inhibit EGFR kinase at a concentration of 6.5 ± 2.91 and 3.65 ± 0.54 µM, respectively. Some of these compounds showed effects on proliferation, which were also then evaluated against four different human cancer cell lines, that is, MCF‐7 (breast cancer), A549 (non‐small‐cell lung tumor), HCT‐116 (colon cancer), and SiHa cells (cancerous tissues of the cervix uteri). The results showed that certain synthetic compounds showed significant inhibitor activity; compounds 6m and 6n were more cytotoxic than doxorubicin against A549 cancer cells, with IC50 values of 10.3 ± 1.07 and 4.6 ± 0.57 µM, respectively. Additionally, compounds 6m and 6n induced apoptosis in A549 cancer cells, as evidenced by 4′,6‐diamidino‐2‐phenylindole (DAPI) staining and phase‐contrast microscopy. Potency to induce apoptosis by compound 6n was further confirmed by fluorescence‐activated cell sorting using Annexin V‐FITC and propidium iodide labeling. Compound 6n showed normal cardiomyocytes with no marked sign of pyknotic nuclei in cardiomyopathy and also normal histological appearance of the renal cortex when compared with that of control. Results of molecular docking studies suggested that compounds 6m and 6n can bind to the hinge region of the adenosine triphosphate‐binding site of EGFR kinase, like the standard drug erlotinib. Therefore, the present study suggests that compounds 6m and 6n have potent in vitro antitumor activities against the human non‐small‐cell lung tumor cell line A549, which can be further explored in other cancer cell lines and in animal studies.

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“…Filtered, washed with water, dried and recyrstallized from aqueous ethanol to obtain a yellow solid product. [ 35 ]…”

Section: Methodsmentioning

confidence: 99%

3′‐(4‐(Benzyloxy)phenyl)‐1′‐phenyl‐5‐(heteroaryl/aryl)‐3,4‐dihydro‐1′H,2H‐[3,4′‐bipyrazole]‐2‐carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies

Nawaz

Alam

Perwez

et al. 2020

Archiv der Pharmazie

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“…TLC (40:60) (ethyl acetate/n-hexane). Compounds (I) a and (I) b Preparation by workers Suwito et al [27] and Gan et al [28] respectively . General method for synthesis of cyclohexenone derivatives (II) a-d .…”

Section: Ghali and Tommamentioning

confidence: 99%

Synthesis and Characterization of Indazol-3-one and Thioxo Pyrimidines Derivatives from Mono and Twin Chalcones

Ghali

Tomma

2017

ijs

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This work involved synthesis and characterization of new mono and twin fused pyrazolone(indazol-3-one) (IV) a-d and thioxo pyrimidine (III) a-d derivatives from Chalcones (mono(I) a,b and twin(I) c,d ) The synthesis of mono chalcones (I) a,b includes the reaction of (p-methoxy or p-methyl) benzaldehyde with 4-amino acetophenone while the twin acetophenone with p-methoxy benzaldehyde to produce twin chalcones (I) c,d , then converted it by Robinson annulations reaction to form the corresponding derivatives (II) a-d afterward reflux the cyclohexenones with hydrazine and some drops of GAA lead to form indazole derivatives (IV) a-d . Pyrimidines were synthesized via the reaction of chalcones with thiourea in NaOH and 80% ethanol. All these compounds are characterized by FT-IR spectroscopy and some of them by 1 HNMR spectroscopy.

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“…Due to their wide spectrum of pharmacological properties, such as antioxidant [2], antihepatotoxic [3], neuroprotective [4], antibacterial [5][6][7][8], inhibitor of topoisomerase I [9], antimalarial [10,11], and anticancer [12], chalcones attract many researchers to develop efficient synthetic methods and to gain various structural variations of chalcones unavailable in nature. In general, chalcones are synthesized by Claisen-Schmidt condensation.…”

Section: Introductionmentioning

confidence: 99%

4-({4-[(2E)-3-(2,5-Dimethoxyphenyl)prop-2-enoyl]phenyl}amino)-4-oxobutanoic Acid

Suwito¹,

Haq²,

Rahmah³

et al. 2017

Molbank

Self Cite

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Abstract:A dimethoxy amide chalcone has been synthesized in a two-step reaction. First, an amine chalcone was synthesized by the reaction of 4 -aminoacetophenone and 2,5-dimethoxybenzaldehyde using 40% NaOH solution as a catalyst in ethanol, and then followed by amidation through the reaction of the formed chalcone and succinic anhydride. The structure of the target compound was established by FTIR, HR-MS, 1 H-and 13 C-NMR, and 2D-NMR spectral analysis.

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Design and Synthesis of Chalcone Derivatives as Inhibitors of the Ferredoxin — Ferredoxin-NADP+ Reductase Interaction of Plasmodium falciparum: Pursuing New Antimalarial Agents

Cited by 51 publications

References 19 publications

3′‐(4‐(Benzyloxy)phenyl)‐1′‐phenyl‐5‐(heteroaryl/aryl)‐3,4‐dihydro‐1′H,2H‐[3,4′‐bipyrazole]‐2‐carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies

3′‐(4‐(Benzyloxy)phenyl)‐1′‐phenyl‐5‐(heteroaryl/aryl)‐3,4‐dihydro‐1′H,2H‐[3,4′‐bipyrazole]‐2‐carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies

Synthesis and Characterization of Indazol-3-one and Thioxo Pyrimidines Derivatives from Mono and Twin Chalcones

4-({4-[(2E)-3-(2,5-Dimethoxyphenyl)prop-2-enoyl]phenyl}amino)-4-oxobutanoic Acid

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