Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives
To identify new candidate anticancer compounds, we here report the synthesis of benzimidazole derivatives: diethyl 2,2′-(2-oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) diacetate and its arylideneacetohydrazide derivatives, using ultrasonic irradiati...
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2022-03-01
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| author | Manel Dhahri Firdos Alam Khan Abdul-Hamid Emwas Rua B. Alnoman Mariusz Jaremko Nadjet Rezki Mohamed Reda Aouad Mohamed Hagar |
| author_facet | Manel Dhahri Firdos Alam Khan Abdul-Hamid Emwas Rua B. Alnoman Mariusz Jaremko Nadjet Rezki Mohamed Reda Aouad Mohamed Hagar |
| author_sort | Manel Dhahri |
| collection | DOAJ |
| description | To identify new candidate anticancer compounds, we here report the synthesis of benzimidazole derivatives: diethyl 2,2′-(2-oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) diacetate and its arylideneacetohydrazide derivatives, using ultrasonic irradiation and conventional heating. The compounds were confirmed by Nuclear magnetic resonance (NMR) (JEOL, Tokyo, Japan) and Fourier transform infrared spectroscopy (FTIR) spectroscopy (Thermoscientific, Waltham, MA, USA). The molecular structure and electronic properties of the studied compounds were predicted for the acetohydrazide hydrazones. These compounds exist as a mixture of configurational and conformational isomerism as well as amido-amidic acid tautomerism. The NMR spectral data proved the predominance of <i>syn-E</i> amido isomers. In addition, density functional theory (DFT) predicted stability in the gas phase and showed that <i>syn-E</i> amido isomers are the most stable in the presence of an electron donating group, while the anti-isomer is the most stable in the presence of electron-attracting substituents. The anticancer activity of these synthetic compounds <b>6a</b>, <b>6b</b> and <b>6c</b> towards both colon cancer (HCT-116) and cervical cancer (HeLa) cells was examined by MTT assay and DAPI staining. The MTT assay revealed a strong antiproliferative effect against the cancer cells at low concentrations, and interestingly, no significant inhibitory action against the non-cancerous cell line, HEK-293. The IC50 values for HCT-116 were 29.5 + 4.53 µM, 57.9 + 7.01 µM and 40.6 + 5.42 µM for <b>6a</b>, <b>6b</b>, and <b>6c</b>, respectively. The IC50 values for HeLa cells were 57.1 + 6.7 µM, 65.6 + 6.63 µM and 33.8 + 3.54 µM for <b>6a</b>, <b>6b</b>, and <b>6c</b>, respectively. DAPI staining revealed that these synthesized benzimidazole derivatives caused apoptotic cell death in both the colon and cervical cancer cells. Thus, these synthetic compounds demonstrate encouraging anticancer activity as well as being safe for normal human cells, making them attractive candidates as anticancer agents. |
| first_indexed | 2024-03-09T11:40:40Z |
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| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-09T11:40:40Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-d6a68fcadda440baae87c98f591f5ec22023-11-30T23:33:37ZengMDPI AGMaterials1996-19442022-03-01157254410.3390/ma15072544Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide DerivativesManel Dhahri0Firdos Alam Khan1Abdul-Hamid Emwas2Rua B. Alnoman3Mariusz Jaremko4Nadjet Rezki5Mohamed Reda Aouad6Mohamed Hagar7Biology Department, Faculty of Science Yanbu, Taibah University, Yanbu El-Bahr 46423, Saudi ArabiaDepartment of Stem Cell Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaCore Labs, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi ArabiaChemistry Department, Faculty of Science, Taibah University, Yanbu Branch, Yanbu 46423, Saudi ArabiaSmart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaDepartment of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi ArabiaChemistry Department, Faculty of Science, Taibah University, Yanbu Branch, Yanbu 46423, Saudi ArabiaTo identify new candidate anticancer compounds, we here report the synthesis of benzimidazole derivatives: diethyl 2,2′-(2-oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) diacetate and its arylideneacetohydrazide derivatives, using ultrasonic irradiation and conventional heating. The compounds were confirmed by Nuclear magnetic resonance (NMR) (JEOL, Tokyo, Japan) and Fourier transform infrared spectroscopy (FTIR) spectroscopy (Thermoscientific, Waltham, MA, USA). The molecular structure and electronic properties of the studied compounds were predicted for the acetohydrazide hydrazones. These compounds exist as a mixture of configurational and conformational isomerism as well as amido-amidic acid tautomerism. The NMR spectral data proved the predominance of <i>syn-E</i> amido isomers. In addition, density functional theory (DFT) predicted stability in the gas phase and showed that <i>syn-E</i> amido isomers are the most stable in the presence of an electron donating group, while the anti-isomer is the most stable in the presence of electron-attracting substituents. The anticancer activity of these synthetic compounds <b>6a</b>, <b>6b</b> and <b>6c</b> towards both colon cancer (HCT-116) and cervical cancer (HeLa) cells was examined by MTT assay and DAPI staining. The MTT assay revealed a strong antiproliferative effect against the cancer cells at low concentrations, and interestingly, no significant inhibitory action against the non-cancerous cell line, HEK-293. The IC50 values for HCT-116 were 29.5 + 4.53 µM, 57.9 + 7.01 µM and 40.6 + 5.42 µM for <b>6a</b>, <b>6b</b>, and <b>6c</b>, respectively. The IC50 values for HeLa cells were 57.1 + 6.7 µM, 65.6 + 6.63 µM and 33.8 + 3.54 µM for <b>6a</b>, <b>6b</b>, and <b>6c</b>, respectively. DAPI staining revealed that these synthesized benzimidazole derivatives caused apoptotic cell death in both the colon and cervical cancer cells. Thus, these synthetic compounds demonstrate encouraging anticancer activity as well as being safe for normal human cells, making them attractive candidates as anticancer agents.https://www.mdpi.com/1996-1944/15/7/2544ultrasonic synthesisbenzimidazole-acetohydrazideconfigurational-conformational-DFT studyanticancer agentcolon cancercervical cancer |
| spellingShingle | Manel Dhahri Firdos Alam Khan Abdul-Hamid Emwas Rua B. Alnoman Mariusz Jaremko Nadjet Rezki Mohamed Reda Aouad Mohamed Hagar Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives Materials ultrasonic synthesis benzimidazole-acetohydrazide configurational-conformational-DFT study anticancer agent colon cancer cervical cancer |
| title | Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives |
| title_full | Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives |
| title_fullStr | Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives |
| title_full_unstemmed | Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives |
| title_short | Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1<i>H</i>-benzo[<i>d</i>]imidazole-1,3(2<i>H</i>)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives |
| title_sort | synthesis dft molecular geometry and anticancer activity of symmetrical 2 2 2 oxo 1 i h i benzo i d i imidazole 1 3 2 i h i diyl diacetate and its arylideneacetohydrazide derivatives |
| topic | ultrasonic synthesis benzimidazole-acetohydrazide configurational-conformational-DFT study anticancer agent colon cancer cervical cancer |
| url | https://www.mdpi.com/1996-1944/15/7/2544 |
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