Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study
Hydrazone is a bioactive pharmacophore that can be used to design antitumor agents. We synthesised a series of hydrazones (compounds 4–24) incorporating a 4-methylsulfonylbenzene scaffold and analysed their potential antitumor activity. Compounds 6, 9, 16, and 20 had the most antitumor activity with...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1924698 |
| _version_ | 1818954338308980736 |
|---|---|
| author | Alaa A.-M. Abdel-Aziz Adel S. El-Azab Nawaf A. AlSaif Ahmad J. Obaidullah Abdulrahman M. Al-Obaid Ibrahim A. Al-Suwaidan |
| author_facet | Alaa A.-M. Abdel-Aziz Adel S. El-Azab Nawaf A. AlSaif Ahmad J. Obaidullah Abdulrahman M. Al-Obaid Ibrahim A. Al-Suwaidan |
| author_sort | Alaa A.-M. Abdel-Aziz |
| collection | DOAJ |
| description | Hydrazone is a bioactive pharmacophore that can be used to design antitumor agents. We synthesised a series of hydrazones (compounds 4–24) incorporating a 4-methylsulfonylbenzene scaffold and analysed their potential antitumor activity. Compounds 6, 9, 16, and 20 had the most antitumor activity with a positive cytotoxic effect (PCE) of 52/59, 27/59, 59/59, and 59/59, respectively, while compounds 5, 10, 14, 15, 18, and 19 had a moderate antitumor activity with a PCE of 11/59–14/59. Compound 20 was the most active and had a mean 50% cell growth inhibition (GI50) of 0.26 µM. Compounds 9 and 20 showed the highest inhibitory activity against COX-2, with a half-maximal inhibitory concentration (IC50) of 2.97 and 6.94 μM, respectively. Compounds 16 and 20 significantly inhibited EGFR (IC50 = 0.2 and 0.19 μM, respectively) and HER2 (IC50 = 0.13 and 0.07 μM, respectively). Molecular docking studies of derivatives 9, 16, and 20 into the binding sites of COX-2, EGFR, and HER2 were carried out to explore the interaction mode and the structural requirements for antitumor activity. |
| first_indexed | 2024-12-20T10:20:35Z |
| format | Article |
| id | doaj.art-f2cef13a3c0140699e1966145b1894a6 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-20T10:20:35Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-f2cef13a3c0140699e1966145b1894a62022-12-21T19:43:56ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-013611520153810.1080/14756366.2021.19246981924698Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking studyAlaa A.-M. Abdel-Aziz0Adel S. El-Azab1Nawaf A. AlSaif2Ahmad J. Obaidullah3Abdulrahman M. Al-Obaid4Ibrahim A. Al-Suwaidan5Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud UniversityHydrazone is a bioactive pharmacophore that can be used to design antitumor agents. We synthesised a series of hydrazones (compounds 4–24) incorporating a 4-methylsulfonylbenzene scaffold and analysed their potential antitumor activity. Compounds 6, 9, 16, and 20 had the most antitumor activity with a positive cytotoxic effect (PCE) of 52/59, 27/59, 59/59, and 59/59, respectively, while compounds 5, 10, 14, 15, 18, and 19 had a moderate antitumor activity with a PCE of 11/59–14/59. Compound 20 was the most active and had a mean 50% cell growth inhibition (GI50) of 0.26 µM. Compounds 9 and 20 showed the highest inhibitory activity against COX-2, with a half-maximal inhibitory concentration (IC50) of 2.97 and 6.94 μM, respectively. Compounds 16 and 20 significantly inhibited EGFR (IC50 = 0.2 and 0.19 μM, respectively) and HER2 (IC50 = 0.13 and 0.07 μM, respectively). Molecular docking studies of derivatives 9, 16, and 20 into the binding sites of COX-2, EGFR, and HER2 were carried out to explore the interaction mode and the structural requirements for antitumor activity.http://dx.doi.org/10.1080/14756366.2021.1924698hydrazones synthesisantitumor activitycell cycle analysisenzymatic assaycox-2 inhibitionegfr inhibitionher2 inhibitionmolecular docking |
| spellingShingle | Alaa A.-M. Abdel-Aziz Adel S. El-Azab Nawaf A. AlSaif Ahmad J. Obaidullah Abdulrahman M. Al-Obaid Ibrahim A. Al-Suwaidan Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study Journal of Enzyme Inhibition and Medicinal Chemistry hydrazones synthesis antitumor activity cell cycle analysis enzymatic assay cox-2 inhibition egfr inhibition her2 inhibition molecular docking |
| title | Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study |
| title_full | Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study |
| title_fullStr | Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study |
| title_full_unstemmed | Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study |
| title_short | Synthesis, potential antitumor activity, cell cycle analysis, and multitarget mechanisms of novel hydrazones incorporating a 4-methylsulfonylbenzene scaffold: a molecular docking study |
| title_sort | synthesis potential antitumor activity cell cycle analysis and multitarget mechanisms of novel hydrazones incorporating a 4 methylsulfonylbenzene scaffold a molecular docking study |
| topic | hydrazones synthesis antitumor activity cell cycle analysis enzymatic assay cox-2 inhibition egfr inhibition her2 inhibition molecular docking |
| url | http://dx.doi.org/10.1080/14756366.2021.1924698 |
| work_keys_str_mv | AT alaaamabdelaziz synthesispotentialantitumoractivitycellcycleanalysisandmultitargetmechanismsofnovelhydrazonesincorporatinga4methylsulfonylbenzenescaffoldamoleculardockingstudy AT adelselazab synthesispotentialantitumoractivitycellcycleanalysisandmultitargetmechanismsofnovelhydrazonesincorporatinga4methylsulfonylbenzenescaffoldamoleculardockingstudy AT nawafaalsaif synthesispotentialantitumoractivitycellcycleanalysisandmultitargetmechanismsofnovelhydrazonesincorporatinga4methylsulfonylbenzenescaffoldamoleculardockingstudy AT ahmadjobaidullah synthesispotentialantitumoractivitycellcycleanalysisandmultitargetmechanismsofnovelhydrazonesincorporatinga4methylsulfonylbenzenescaffoldamoleculardockingstudy AT abdulrahmanmalobaid synthesispotentialantitumoractivitycellcycleanalysisandmultitargetmechanismsofnovelhydrazonesincorporatinga4methylsulfonylbenzenescaffoldamoleculardockingstudy AT ibrahimaalsuwaidan synthesispotentialantitumoractivitycellcycleanalysisandmultitargetmechanismsofnovelhydrazonesincorporatinga4methylsulfonylbenzenescaffoldamoleculardockingstudy |