Reactions of Fe3(CO)12 with cyclic diselenides or diselenocyanatoalkanes produced two different products, namely the dinuclear [Fe2(CO)6{μ‐(SeCH2)2(CH2)n}] (n= 5 (1 a), 6 (1 b), 7 (1 c), 8 (1 d)) and the tetranuclear models [Fe2(CO)6{μ‐(SeCH2)2(CH2)n}]2 (n=5 (2 a), 6 (2 b), 7 (2 c), 8 (2 d)). The resulting complexes were fully characterized by a variety of analytical techniques (NMR spectroscopy, elemental analysis, mass spectrometry) and by X‐ray structure determination of complexes 1 c, 1 d, 2 c and 2 d. Furthermore, we investigated the redox properties and the catalytic behaviour of complexes 1 a‐d in the presence of acetic acid (AcOH) as a source of protons.
The emergence of phosphatidylinositol 3-kinase (PI3Kα) in cancer development has accentuated its significance as a potential target for anticancer drug design. Twenty one derivatives of N-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using NMR (1H and 13C) and HRMS. The derivatives displayed inhibitory activity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines: compounds 8 (IC50 Caco-2 = 98 µM, IC50 HCT-116 = 337 µM) and 16 (IC50 Caco-2 = 13 µM, IC50 HCT-116 = 240.2 µM). Results showed that compound 16 significantly affected the gene encoding AKT, BAD, and PI3K. The induced-fit docking (IFD) studies against PI3Kα demonstrated that the scaffold accommodates the kinase domains and forms H-bonds with significant binding residues.
Cancer is one of the leading causes of death worldwide, and it has a major impact on public health. Phosphatidylinositol 3‐kinase (PI3Kα) has been recognized as a promising drug target for developing anticancer agents. Herein, a series of N‐phenyl‐6‐fluoro‐4‐hydroxy‐2‐quinolone‐3‐carboxamides was developed to target PI3Kα. All synthesized compounds were characterized using FT‐IR, NMR (1H and 13C) and elemental analysis. All synthesized chemical analogues exerted distinctive anticancer activity. They inhibited the growth of human epithelial colorectal adenocarcinoma (Caco‐2) with IC50 values between 48.63–378 μM, and human colon cancer (HCT‐116) cell lines with IC50 values between 44–664 μM. Computational modelling studies provided important biological insight. Induced‐fit docking (IFD) studies showed that the synthesized chemical analogues fit the kinase catalytic domains and form a significant H‐bond interaction network with key amino acids at the biding site. Furthermore, cheminformatics analyses indicated that all synthesized compounds were drug‐like permitting further animal testing or clinical development.
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.
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