Am Synthesis, Docking Study and  In vitro Anticancer Evaluation of Some New Flurbiprofen  Derivatives Against MCF-7  and WRL-68 Cell Lines

Hmood, Kasim S.; Kubba, Ammar A. Razzak Mahmood; Al-Bayati, Redha I.; Saleh, Abdulrahman M.

doi:10.22146/ijp.730

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…Molecular docking was performed as described previously (El‐Adl et al, 2021; Hmood & Kubba, 2021b; Hussein et al, 2023; Schüttelkopf & Van Aalten, 2004).…”

Section: Methodsmentioning

confidence: 99%

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Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3‐phenoxybenzoic acid as VEGFR‐2 inhibitors

Heriz,

Mahmood,

Yasin

et al. 2024

Drug Development Research

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Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3‐phenoxybenzoic acid derivatives, including 1,3,4‐oxadiazole derivatives (4a–d) and benzamides derivatives (5a–e) were synthesized; their chemical structures were confirmed by Fourier‐transform infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectra; and various physicochemical properties were determined. The antiproliferative activities of the new derivatives were evaluated by means of the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Three compounds (4b, 4c, and 4d) exhibited cytotoxicity against two of the three cell lines tested, five compounds (3, 4a, 5a, 5b, and 5e) were toxic to one cell line, while two compounds (5c and 5d) were not cytotoxic to any of the three cell lines tested in the current study. Based on docking scores, MTT assay findings, and vascular endothelial growth factor receptor 2 (VEGFR‐2) kinase activity data, Compound 4d was selected for further biological investigation. Flow cytometry was used to determine the mode of cell death (apoptosis vs. necrosis) and the effect on cell cycle progression. Compound 4d arrested HepG2 hepatocellular carcinoma cells in the G2/M phase and activated both the intrinsic and extrinsic apoptosis pathways. In conclusion, Compound 4d has shown promising results for future research as a potent VEGFR‐2 tyrosine kinase inhibitor.

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“…Molecular docking was performed as described previously (El‐Adl et al, 2021; Hmood & Kubba, 2021b; Hussein et al, 2023; Schüttelkopf & Van Aalten, 2004).…”

Section: Methodsmentioning

confidence: 99%

“…2.1.2 | Synthesis of methyl 3-phenoxybenzoate (Compound 1) (Abbas et al, 2021;Hmood et al, 2021a;Tawfeeq & Qassir, 2020) In 30 mL of abs. MeOH, 3-phenyl benzoic acid (10 mmol, 2.14 g) was dissolved, concentrated H 2 SO 4 was introduced gradually, and a 12 h reflux period was followed by TLC monitoring of the resultant mixture.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3‐phenoxybenzoic acid as VEGFR‐2 inhibitors

Heriz,

Mahmood,

Yasin

et al. 2024

Drug Development Research

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“…Using the web application pre-ADMET (https://preadmet.qsarhub.com/adme/), the pharmacokinetic characteristics of the synthesised fused coumarin compounds SA0-SA7 were analysed in silico. This analysis involved their absorption, distribution, metabolism, and excretion [29,30].…”

Section: Theoretical Pharmacokinetic Factorsmentioning

confidence: 99%

Untitled

2022

J. Med. Chem. Sci.

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This work involves the synthesis of eight novel fused coumarin compounds, which were confirmed by various spectrophotometers and then, assessed for their apoptotic-inducing and free radical-quenching activities. The pharmacokinetic parameters were evaluated in silico using pre-ADMET, a free online program. The apoptotic-inducing activity was tested against six tumorigenic cell lines. Also, their safety against normal cells was examined. The free radical-quenching activity was assessed by checking these compounds' ability to eliminate DDPT and hydroxyl moieties. Pharmacokinetic investigations showed that the synthesized fused coumarin compounds have excellent penetration across the GIT mucosa and most of them have poor penetration across the blood-brain barrier. These findings suggest good oral bioavailability along with low neurological toxicity profiles. The evaluation of the apoptotic-inducing activity revealed that all of the compounds have weaker activity as compared to the reference. Among these compounds, SA4 was the most potent one. Nevertheless, all of these new compounds had an excellent safety profile against normal cells. On the other hand, the assessment of the free radical-quenching activity of these synthesized compounds also indicated that all of them were less active than the reference. In this field, SA0 was the strongest free radical-quenching compound. From these realizations, along with the apparent safety and good pharmacokinetic characteristics in accordance with the in silico study, compounds SA4 and SA0 are considered the most promising agents. The authors hope that these new fused coumarin compounds can be utilized in the coming years for the production of new powerful drugs with apoptoticinducing and free radical-quenching potentials which can help in the battle against many diseases.

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“…= 0.9, AT-IR (v = cm -1 ): 3313 str of sec. (NH 2 ); 3000-3100 (Ar-CH) str, 2981 str of methyl (CH), 2930 str of methelyne (CH), 1685 Synthesis of 2- ((3-(trifluoromethyl)phenyl)amino) benzohydrazide, (hydrazide) (Abbas et al 2015;Hmood et al 2021) Flufenamic ethyl ester, (0.037 mol, 5.6 g) and hydrazine hydrate 99.5% (an excess amount of 0.185 mol, 9.0 mL) were added to 40 mL of EtOH into 250 mL round bottom flask and the mixture was first refluxed at 80 °C for 12 h after which, it was set to be stirred overnight at room temperature (RT). It was noticed that the colorless solution changed into pale pink with the time.…”

Section: Chemical Synthesismentioning

confidence: 99%

Synthesis, docking study, and in vitro anticancer evaluation of new flufenamic acid derivatives

Al-Bayati¹,

Mahmood²,

Al-Mazaydeh³

et al. 2021

PHAR

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Novel compounds (6–10) were synthesized and confirmed by spectroscopic analysis, including AT-IR, 1HNMR and CHNS. Their cytotoxic effect was evaluated by MTT assay against two cancer cell lines and two normal cell types. Compound 7 exhibited anticancer activity against MCF-7 breast cancer cell line (GI50 = 63.9 µg/ml, 148 µM), without any effect against A549 lung cancer cells, or the normal cells. Compound 7 caused cytotoxicity in MCF-7 breast cancer cells by apoptotic cell death, as suggested by fragmented nuclei after DAPI staining and agarose gel electrophoresis. In addition, treating MCF-7 cells with compound 7 resulted in an increase in the level of caspase 9 mRNA level, and its activation. Moreover, compound 7-treated MCF-7 cells showed enhanced cytochrome c release from the mitochondria to the cytosol, signifying an induction of the intrinsic apoptotic pathway. Finally, compound 7 exhibited epidermal growth factor receptor (EGFR) kinase inhibitory activity at (EC50 = 0.13 µM), which was matched by molecular docking studies that showed compound 7 might be an important EGFR kinase inhibitor.

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Am Synthesis, Docking Study and In vitro Anticancer Evaluation of Some New Flurbiprofen Derivatives Against MCF-7 and WRL-68 Cell Lines

Cited by 6 publications

References 27 publications

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3‐phenoxybenzoic acid as VEGFR‐2 inhibitors

Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3‐phenoxybenzoic acid as VEGFR‐2 inhibitors

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Synthesis, docking study, and in vitro anticancer evaluation of new flufenamic acid derivatives

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