Design, Synthesis, Anticancer Evaluation, Enzymatic Assays, and a Molecular Modeling Study of Novel Pyrazole–Indole Hybrids
| العنوان: | Design, Synthesis, Anticancer Evaluation, Enzymatic Assays, and a Molecular Modeling Study of Novel Pyrazole–Indole Hybrids |
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| المؤلفون: | Hanem M. Awad, Mohamed F. Mady, Gaber O. Moustafa, Eman S. Nossier, Ashraf S. Hassan |
| المصدر: | ACS Omega 12361-12374 ACS Omega, Vol 6, Iss 18, Pp 12361-12374 (2021) |
| بيانات النشر: | American Chemical Society (ACS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Indole test, Molecular model, kreft, Chemistry, General Chemical Engineering, Isatin, Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762 [VDP], General Chemistry, Pyrazole, Article, In vitro, celler, chemistry.chemical_compound, Biochemistry, peptider, proteiner, medicine, Doxorubicin, MTT assay, Cytotoxicity, QD1-999, Matematikk og Naturvitenskap: 400::Kjemi: 440 [VDP], medicine.drug |
| الوصف: | The molecular hybridization concept has recently emerged as a powerful approach in drug discovery. A series of novel indole derivatives linked to the pyrazole moiety were designed and developed via a molecular hybridization protocol as antitumor agents. The target compounds (5a–j and 7a–e) were prepared by the reaction of 5-aminopyrazoles (1a–e) with N-substituted isatin (4a,b) and 1H-indole-3-carbaldehyde (6), respectively. All products were characterized via several analytical and spectroscopic techniques. Compounds (5a–j and 7a–e) were screened for their cytotoxicity activities in vitro against four human cancer types [human colorectal carcinoma (HCT-116), human breast adenocarcinoma (MCF-7), human liver carcinoma (HepG2), and human lung carcinoma (A549)] using the MTT assay. The obtained results showed that the newly synthesized compounds displayed good-to-excellent antitumor activity. For example, 5-((1H-indol-3-yl)methyleneamino)-N-phenyl-3-(phenylamino)-1H-pyrazole-4-carboxamide (7a) and 5-((1H-indol-3-yl)methyleneamino)-3-(phenylamino)-N-(4-methylphenyl)-1H-pyrazole-4-carboxamide (7b) provided excellent anticancer inhibition performance against the HepG2 cancer cell line with IC50 values of 6.1 ± 1.9 and 7.9 ± 1.9 μM, respectively, compared to the standard reference drug, doxorubicin (IC50 = 24.7 ± 3.2 μM). The two powerful anticancer compounds (7a and 7b) were further subjected to cell cycle analysis and apoptosis investigation in HepG2 using flow cytometry. We have also studied the enzymatic assay of these two compounds against some enzymes, namely, caspase-3, Bcl-2, Bax, and CDK-2. Interestingly, the molecular docking study revealed that compounds 7a and 7b could well embed in the active pocket of the CDK-2 enzyme via different interactions. Overall, the prepared pyrazole–indole hybrids (7a and 7b) can be proposed as strong anticancer candidate drugs against various cancer cell lines. |
| وصف الملف: | application/pdf |
| تدمد: | 2470-1343 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b145b80ab49b0f764e9e700f335ae27 https://doi.org/10.1021/acsomega.1c01604 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....2b145b80ab49b0f764e9e700f335ae27 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 24701343 |
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