Izvorni znanstveni članak

https://doi.org/10.2478/acph-2021-0043

New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation

DIMA A. SABBAH orcid.org/0000-0003-1428-5097 ; Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733 Jordan
BARA’A A. AL-AZAIDEH ; Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733 Jordan
WAMIDH H. TALIB ; Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, P.O. Box 166, Amman 11931 Jordan
RIMA HAJJO ; Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733 Jordan
KAMAL SWEIDAN ; Department of Chemistry, The University of Jordan, Amman 11942, Jordan
AYA M. AL-ZUHEIRI ; Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733 Jordan
GHASSAN ABU SHEIKHA
SAWSAN SHRAIM ; Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733 Jordan

Sažetak

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.

Ključne riječi

sulfonylhydrazones; antitumor; HCT-116; PI3Kα-inhibitors; cheminformatics; docking

Hrčak ID:

253953

URI

https://hrcak.srce.hr/253953

Datum izdavanja:

31.12.2021.

Posjeta: 1.677 *