Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrile
The target compound 3-amino-1-(2,5-d ichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]-chromene-2-carbonitrile <b>(4)</b> was synthesized via a reaction of 6-methoxynaphthalen-2-ol <b>(1)</b>, 2,5-dichlorobenzaldehyde <b>(2)</b>, and malon...
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MDPI AG
2021-02-01
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| Series: | Crystals |
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| Online Access: | https://www.mdpi.com/2073-4352/11/2/184 |
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| author | Menna El Gaafary Tatiana Syrovets Hany M. Mohamed Ahmed A. Elhenawy Ahmed M. El-Agrody Abd El-Galil E. Amr Hazem A. Ghabbour Abdulrahman A. Almehizia |
| author_facet | Menna El Gaafary Tatiana Syrovets Hany M. Mohamed Ahmed A. Elhenawy Ahmed M. El-Agrody Abd El-Galil E. Amr Hazem A. Ghabbour Abdulrahman A. Almehizia |
| author_sort | Menna El Gaafary |
| collection | DOAJ |
| description | The target compound 3-amino-1-(2,5-d ichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]-chromene-2-carbonitrile <b>(4)</b> was synthesized via a reaction of 6-methoxynaphthalen-2-ol <b>(1)</b>, 2,5-dichlorobenzaldehyde <b>(2)</b>, and malononitrile <b>(3)</b> in ethanolic piperidine solution under microwave irradiation. The newly synthesized <i>β</i>-enaminonitrile was characterized by FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, mass spectroscopy, elemental analysis and X-ray diffraction data. Its cytotoxic activity was evaluated against three different human cancer cell lines MDA-MB-231, A549, and MIA PaCa-2 in comparison to the positive controls etoposide and camptothecin employing the XTT cell viability assay. The analysis of the Hirshfeld surface was utilized to visualize the reliability of the crystal package. The obtained results confirmed that the tested molecule revealed promising cytotoxic activities against the three cancer cell lines. Furthermore, theoretical calculations (DFT) were carried out with the Becke3-Lee-Yang-parr (B3LYP) level using 6-311++G(d,p) basis. The optimization geometry for molecular structures was in agreement with the X-ray structure data. The HOMO-LUMO energy gap of the studied system was discussed. The intermolecular-interactions were studied through analysis of the topological-electron-density(r) using the QTAIM and NCI methods. The novel compound exhibited favorable ADMET properties and its molecular modeling analysis showed strong interaction with DNA methyltransferase 1. |
| first_indexed | 2024-03-09T00:54:51Z |
| format | Article |
| id | doaj.art-c27a2216360549dc90cd801f0d988f33 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-09T00:54:51Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Crystals |
| spelling | doaj.art-c27a2216360549dc90cd801f0d988f332023-12-11T16:57:52ZengMDPI AGCrystals2073-43522021-02-0111218410.3390/cryst11020184Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrileMenna El Gaafary0Tatiana Syrovets1Hany M. Mohamed2Ahmed A. Elhenawy3Ahmed M. El-Agrody4Abd El-Galil E. Amr5Hazem A. Ghabbour6Abdulrahman A. Almehizia7Department of Pharmacognosy, College of Pharmacy, Cairo University, Cairo 11562, EgyptInstitute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, 89081 Ulm, GermanyChemistry Department, Faculty of Science, Jazan University, Jazan 45142, Saudi ArabiaChemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, EgyptChemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo 11884, EgyptPharmaceutical Chemistry Department, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, EgyptPharmaceutical Chemistry Department, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaThe target compound 3-amino-1-(2,5-d ichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]-chromene-2-carbonitrile <b>(4)</b> was synthesized via a reaction of 6-methoxynaphthalen-2-ol <b>(1)</b>, 2,5-dichlorobenzaldehyde <b>(2)</b>, and malononitrile <b>(3)</b> in ethanolic piperidine solution under microwave irradiation. The newly synthesized <i>β</i>-enaminonitrile was characterized by FT-IR, <sup>1</sup>H NMR, <sup>13</sup>C NMR, mass spectroscopy, elemental analysis and X-ray diffraction data. Its cytotoxic activity was evaluated against three different human cancer cell lines MDA-MB-231, A549, and MIA PaCa-2 in comparison to the positive controls etoposide and camptothecin employing the XTT cell viability assay. The analysis of the Hirshfeld surface was utilized to visualize the reliability of the crystal package. The obtained results confirmed that the tested molecule revealed promising cytotoxic activities against the three cancer cell lines. Furthermore, theoretical calculations (DFT) were carried out with the Becke3-Lee-Yang-parr (B3LYP) level using 6-311++G(d,p) basis. The optimization geometry for molecular structures was in agreement with the X-ray structure data. The HOMO-LUMO energy gap of the studied system was discussed. The intermolecular-interactions were studied through analysis of the topological-electron-density(r) using the QTAIM and NCI methods. The novel compound exhibited favorable ADMET properties and its molecular modeling analysis showed strong interaction with DNA methyltransferase 1.https://www.mdpi.com/2073-4352/11/2/184benzochromenemicrowave irradiationX-raycytotoxic activityDFT molecular orbital calculationsoptimization geometry |
| spellingShingle | Menna El Gaafary Tatiana Syrovets Hany M. Mohamed Ahmed A. Elhenawy Ahmed M. El-Agrody Abd El-Galil E. Amr Hazem A. Ghabbour Abdulrahman A. Almehizia Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrile Crystals benzochromene microwave irradiation X-ray cytotoxic activity DFT molecular orbital calculations optimization geometry |
| title | Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrile |
| title_full | Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrile |
| title_fullStr | Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrile |
| title_full_unstemmed | Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrile |
| title_short | Synthesis, Cytotoxic Activity, Crystal Structure, DFT Studies and Molecular Docking of 3-Amino-1-(2,5-dichlorophenyl)-8-methoxy-1<i>H</i>-benzo[<i>f</i>]chromene-2-carbonitrile |
| title_sort | synthesis cytotoxic activity crystal structure dft studies and molecular docking of 3 amino 1 2 5 dichlorophenyl 8 methoxy 1 i h i benzo i f i chromene 2 carbonitrile |
| topic | benzochromene microwave irradiation X-ray cytotoxic activity DFT molecular orbital calculations optimization geometry |
| url | https://www.mdpi.com/2073-4352/11/2/184 |
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