New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation
Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N’-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effe...
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| Format: | Article |
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2021-12-01
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| Series: | Acta Pharmaceutica |
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| Online Access: | https://doi.org/10.2478/acph-2021-0043 |
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| author | Sabbah Dima A. Al-Azaideh Bara’a A. Talib Wamidh H. Hajjo Rima Sweidan Kamal Al-Zuheiri Aya M. Sheikha Ghassan Abu Shraim Sawsan |
| author_facet | Sabbah Dima A. Al-Azaideh Bara’a A. Talib Wamidh H. Hajjo Rima Sweidan Kamal Al-Zuheiri Aya M. Sheikha Ghassan Abu Shraim Sawsan |
| author_sort | Sabbah Dima A. |
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| description | Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N’-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue. |
| format | Article |
| id | doaj-art-73a2b2a187bf44e68ccc2f1a964cb57c |
| institution | Kabale University |
| issn | 1846-9558 |
| language | English |
| publishDate | 2021-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Acta Pharmaceutica |
| spelling | doaj-art-73a2b2a187bf44e68ccc2f1a964cb57c2025-02-02T09:33:08ZengSciendoActa Pharmaceutica1846-95582021-12-0171454556510.2478/acph-2021-0043New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluationSabbah Dima A.0Al-Azaideh Bara’a A.1Talib Wamidh H.2Hajjo Rima3Sweidan Kamal4Al-Zuheiri Aya M.5Sheikha Ghassan Abu6Shraim Sawsan7Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733JordanDepartment of Clinical Pharmacy and Therapeutics, Applied Science Private University, P.O. Box 166, Amman 11931JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733JordanDepartment of Chemistry, The University of Jordan, Amman 11942, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733JordanPhosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N’-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue.https://doi.org/10.2478/acph-2021-0043sulfonylhydrazonesantitumorhct-116pi3kα-inhibitorscheminformaticsdocking |
| spellingShingle | Sabbah Dima A. Al-Azaideh Bara’a A. Talib Wamidh H. Hajjo Rima Sweidan Kamal Al-Zuheiri Aya M. Sheikha Ghassan Abu Shraim Sawsan New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation Acta Pharmaceutica sulfonylhydrazones antitumor hct-116 pi3kα-inhibitors cheminformatics docking |
| title | New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation |
| title_full | New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation |
| title_fullStr | New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation |
| title_full_unstemmed | New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation |
| title_short | New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation |
| title_sort | new derivatives of sulfonylhydrazone as potential antitumor agents design synthesis and cheminformatics evaluation |
| topic | sulfonylhydrazones antitumor hct-116 pi3kα-inhibitors cheminformatics docking |
| url | https://doi.org/10.2478/acph-2021-0043 |
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