Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents
The development of new approaches for the synthesis of new bioactive heterocyclic derivatives is of the utmost importance for pharmaceutical industry. In this regard, the present study reports the green synthesis of new benzaldazine and ketazine derivatives via the condensation of various carbonyl c...
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MDPI AG
2023-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/9/3869 |
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| author | Mohamed S. Ibrahim Basant Farag Jehan Y. Al-Humaidi Magdi E. A. Zaki Maher Fathalla Sobhi M. Gomha |
| author_facet | Mohamed S. Ibrahim Basant Farag Jehan Y. Al-Humaidi Magdi E. A. Zaki Maher Fathalla Sobhi M. Gomha |
| author_sort | Mohamed S. Ibrahim |
| collection | DOAJ |
| description | The development of new approaches for the synthesis of new bioactive heterocyclic derivatives is of the utmost importance for pharmaceutical industry. In this regard, the present study reports the green synthesis of new benzaldazine and ketazine derivatives via the condensation of various carbonyl compounds (aldehydes and ketones with the 3-(1-hydrazineylideneethyl)-1<i>H</i>-indole using the grinding method with one drop of acetic acid). Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. Furthermore, the anticancer activities of the reported azine derivatives were evaluated against colon, hepatocellular, and breast carcinoma cell lines using the MTT technique with doxorubicin as a reference medication. The findings suggested that the synthesized derivatives exhibited potential anti-tumor activities toward different cell lines. For example, <b>3c</b>, <b>3d</b>, <b>3h</b>, <b>9</b>, and <b>13</b> exhibited interesting activity with an IC<sub>50</sub> value of 4.27–8.15 µM towards the HCT-116 cell line as compared to doxorubicin (IC<sub>50</sub> = 5.23 ± 0.29 µM). In addition, 3c, 3d, 3h, 9, 11, and 13 showed excellent cytotoxic activities (IC<sub>50</sub> = 4.09–9.05 µM) towards the HePG-2 cell line compared to doxorubicin (IC<sub>50</sub> = 4.50 ± 0.20 µM), and 3d, 3h, 9, and 13 demonstrated high potency (IC<sub>50</sub> = 6.19–8.39 µM) towards the breast cell line (MCF-7) as compared to the reference drug (IC<sub>50</sub> = 4.17 ± 0.20 µM). The molecular interactions between derivatives <b>3a-h</b>, <b>7</b>, <b>9</b>, <b>11</b>, <b>13</b>, and the CDK-5 enzyme (PDB ID: 3IG7) were studied further using molecular docking indicating a high level of support for the experimental results. Furthermore, the drug-likeness analysis of the reported derivatives indicated that derivative <b>9</b> (binding affinity = −8.34 kcal/mol) would have a better pharmacokinetics, drug-likeness, and oral bioavailability as compared to doxorubicin (−7.04 kcal/mol). These results along with the structure–activity relationship (SAR) of the reported derivatives will pave the way for the design of additional azines bearing indole with potential anticancer activities. |
| first_indexed | 2024-03-07T23:29:19Z |
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| language | English |
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| spelling | doaj.art-14ac13f6ff7a4ece9e2946e0a97b4b252024-02-20T16:27:18ZengMDPI AGMolecules1420-30492023-05-01289386910.3390/molecules28093869Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer AgentsMohamed S. Ibrahim0Basant Farag1Jehan Y. Al-Humaidi2Magdi E. A. Zaki3Maher Fathalla4Sobhi M. Gomha5Department of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Zagazig University, Zagazig 44519, EgyptDepartment of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaDepartment of Chemistry, Faculty of Science, Islamic University of Madinah, Madinah 42351, Saudi ArabiaThe development of new approaches for the synthesis of new bioactive heterocyclic derivatives is of the utmost importance for pharmaceutical industry. In this regard, the present study reports the green synthesis of new benzaldazine and ketazine derivatives via the condensation of various carbonyl compounds (aldehydes and ketones with the 3-(1-hydrazineylideneethyl)-1<i>H</i>-indole using the grinding method with one drop of acetic acid). Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. Furthermore, the anticancer activities of the reported azine derivatives were evaluated against colon, hepatocellular, and breast carcinoma cell lines using the MTT technique with doxorubicin as a reference medication. The findings suggested that the synthesized derivatives exhibited potential anti-tumor activities toward different cell lines. For example, <b>3c</b>, <b>3d</b>, <b>3h</b>, <b>9</b>, and <b>13</b> exhibited interesting activity with an IC<sub>50</sub> value of 4.27–8.15 µM towards the HCT-116 cell line as compared to doxorubicin (IC<sub>50</sub> = 5.23 ± 0.29 µM). In addition, 3c, 3d, 3h, 9, 11, and 13 showed excellent cytotoxic activities (IC<sub>50</sub> = 4.09–9.05 µM) towards the HePG-2 cell line compared to doxorubicin (IC<sub>50</sub> = 4.50 ± 0.20 µM), and 3d, 3h, 9, and 13 demonstrated high potency (IC<sub>50</sub> = 6.19–8.39 µM) towards the breast cell line (MCF-7) as compared to the reference drug (IC<sub>50</sub> = 4.17 ± 0.20 µM). The molecular interactions between derivatives <b>3a-h</b>, <b>7</b>, <b>9</b>, <b>11</b>, <b>13</b>, and the CDK-5 enzyme (PDB ID: 3IG7) were studied further using molecular docking indicating a high level of support for the experimental results. Furthermore, the drug-likeness analysis of the reported derivatives indicated that derivative <b>9</b> (binding affinity = −8.34 kcal/mol) would have a better pharmacokinetics, drug-likeness, and oral bioavailability as compared to doxorubicin (−7.04 kcal/mol). These results along with the structure–activity relationship (SAR) of the reported derivatives will pave the way for the design of additional azines bearing indole with potential anticancer activities.https://www.mdpi.com/1420-3049/28/9/3869indoleazinescondensationgrindingmolecular dockingCDK-5 and SAR |
| spellingShingle | Mohamed S. Ibrahim Basant Farag Jehan Y. Al-Humaidi Magdi E. A. Zaki Maher Fathalla Sobhi M. Gomha Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents Molecules indole azines condensation grinding molecular docking CDK-5 and SAR |
| title | Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents |
| title_full | Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents |
| title_fullStr | Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents |
| title_full_unstemmed | Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents |
| title_short | Mechanochemical Synthesis and Molecular Docking Studies of New Azines Bearing Indole as Anticancer Agents |
| title_sort | mechanochemical synthesis and molecular docking studies of new azines bearing indole as anticancer agents |
| topic | indole azines condensation grinding molecular docking CDK-5 and SAR |
| url | https://www.mdpi.com/1420-3049/28/9/3869 |
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