Design and synthesis of novel (S)-Naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models

Han, M. İhsan; Atalay, Pinar Buket; Tunc, Cansu Umran; Ünal, Gökhan; Dayan, Serkan; Aydın, Ömer; Küçükgüzel, Ş. Güniz

doi:10.1016/j.bmc.2021.116097

Cited by 37 publications

(21 citation statements)

References 29 publications

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“…In addition to theiranti-inflammatory activity, naproxen derivatives have been explored for anticancer activity [11][12][13][14][15]. For example, Naproxen-based urea and propanamide derivatives have shown promising inhibition in colon cancer cells [16], protection in bladder cancer proliferation [17] and inhibitors of VEGFR-2 and histone deacetylase enzymes [18,19]. Heterocycles form the basic skeleton for a number of molecules of biological interests [20].…”

Section: Generalmentioning

confidence: 99%

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

et al. 2021

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A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15)was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.

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Section: Generalmentioning

confidence: 99%

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

et al. 2021

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“…Several studies were reported for the biological activities of hydrazide-hydrazone structures [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. The hydrazone group has an advantage of blocking the free amine for metabolic stability.…”

Section: Biological Activitymentioning

confidence: 99%

Synthesis, Structure Elucidation and Biological Activity of New Hybrid Hydrazone-Amide Compounds

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AKLAMUZ

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et al. 2022

Cumhuriyet Science Journal

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Bacterial infection today occupies a tremendous place in world health. The infection diseases were kept under control after the development of penicillin and further studies were performed on the development of new antibacterial agents. However, to date, bacterial resistance caused a big failure in the treatment of infectious disease and therefore, development of new antibacterial agents became important for human health. In the present study, we have designed, synthesized and elucidated the structures of new hydrazide-hydrazone compounds and their hybrid amide derivatives. The structures of the compounds were elucidated with spectroscopic methods and their purity were proven by TLC, HPLC-MS analysis. The antibacterial and antifungal activity studies of the novel molecules were investigated on different strains. Among the synthesized compounds, AA3a and AA4a appeared to show promising antibacterial activity. None of the compounds showed significant antifungal activity on Candida albicans. The drug likeness properties and boiled-egg plot analysis were performed for all of the compounds. The novel molecules showed no violation on Lipinski’s rule of five and all the molecules showed good gastrointestinal absorption properties in the in silico studies.

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“…Moreover, tolmetin hydrazide-hydrazones having 2,6-dichlorophenyl moiety exhibited signi cant cytotoxicity and induction of apoptosis in the HT-29 cancer line [4]. A very recent report deals with, the apoptosis-inducing effect and VEGFR-2 inhibition of (S)-2-(6methoxynaphthalen-2-yl)-N'-{(E)-[2-(tri uoromethoxy)phenyl]methylidene} propanehydrazide [5].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

et al. 2022

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In the present study, the various 28 hybrid molecules containing hydrazone and sulfonate moiety were synthesized and characterized by FTIR, 1 H-NMR, 13 C-NMR spectroscopy and LC-MS spectrometry, besides elemental analysis. The compounds were evaluated for their antiproliferative effects against six cancer cell lines, namely A549 (non-small cell lung cancer), MCF-7 (breast cancer), HT-29 (colorectal adenocarcinoma cancer), PC-3 (androgen-independent prostate adenocarcinoma), Hep3B (hepatocellular carcinoma cancer), and HeLa (epitheloid cervix carcinoma cancer). Among all the target compounds, compounds 4g and 4h exhibited more promising effects on MCF-7 cell lines (IC 50 =17.8 mM and 21.2 mM, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by nally activating caspase-9 and caspase-3. The results have been encouraging enough to merit further investigation.

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Design and synthesis of novel (S)-Naproxen hydrazide-hydrazones as potent VEGFR-2 inhibitors and their evaluation in vitro/in vivo breast cancer models

Cited by 37 publications

References 29 publications

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

Synthesis, Structure Elucidation and Biological Activity of New Hybrid Hydrazone-Amide Compounds

Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

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