New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation
| Autor: | DIMA A. SABBAH, BARA’A A. AL-AZAIDEH, WAMIDH H. TALIB, RIMA HAJJO, KAMAL SWEIDAN, AYA M. AL-ZUHEIRI, GHASSAN ABU SHEIKHA, SAWSAN SHRAIM |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Acta Pharmaceutica Volume 71 Issue 4 |
| ISSN: | 1846-9558 1330-0075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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