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Thirteen novel isatin‐ampyrone Schiff bases derivatives were synthesized in only two steps of 70%–90% overall yields. In vitro cytotoxic activity of these new Schiff bases against three human tumor cell lines (MCF‐7, A549, and SCOV3) as well as normal breast cell line (MCF‐10A) were evaluated by MTT assay. Structure–activity relationship of the tested compounds revealed that chlorine group at C‐5 position of the isatin ring significantly increased the cytotoxic activity. This study generally led to introduce a highly active molecule (M12) with IC50 values of 5.12, 25.5, and 12.9 μΜ, on MCF‐7, A549, and SCOV3, respectively. Furthermore, molecular docking studies of the synthesized compounds were also done to investigate their binding modes towards VEGFR‐2 and JNK3‐MAP kinase as the main targets for isatin‐containing anticancer agents. Binding free energy values of the compounds showed positive correlation with their cytotoxic activities. To confirm the docking results, molecular docking simulations of potent compound (M12) against VEGFR‐2 and JNK3 MAP kinase were also performed. According to the cytotoxic results and in silico ADMET predictions together, M12 can be considered as a potent candidate for the future anticancer studies. [ABSTRACT FROM AUTHOR]

Herein, new Pt(ii) complexes [R′2Pt(CNR)2] (1a–c; R′ = Me and 2a–c; R′ = p-tolyl) were synthesized by the reaction of the precursor complexes cis,cis-[Me2Pt(μ-SMe2)2PtMe2], A, and cis-[(p-tolyl)2Pt(SMe2)2], B, with four and two equivalents of different types of isocyanide ligands (CNR; R = a; t-butyl, b; benzyl, and c; cyclohexyl isocyanide), respectively. All complexes were characterized by FTIR and NMR spectroscopies, and the structure of 2b was confirmed by single-crystal X-ray determination. The evaluation of the cytotoxicity of 1a–c and 2a–c against three human cancer cell lines, namely A549 (non-small cell lung cancer cell line), SKOV3 (human ovarian cancer cell line), and MCF-7 (human breast cancer cell line), revealed promising antitumor activities for 1b and 2a in comparison with that of the standard cisplatin. Moreover, 1b effectively rendered apoptosis-inducing activities to the MCF-7 cancer cell line. The electrophoresis mobility shift assays on plasmids as well as molecular docking studies on DNA structures effectively revealed the specific binding site, binding mode, and the best orientation of the complexes to DNA. [ABSTRACT FROM AUTHOR]

In this study, the cytotoxic activities of structurally related cycloplatinated(ii) complexes containing chelating and bridging 1,1′-bis(diphenylphosphino)ferrocene (dppf) ligand derived from a wide range of C^N cyclometalating ligands (vpy = deprotonated 2-vinylpyridine, bzq = deprotonated benzo[h]quinoline, bpy = deprotonated 2,2′-bipyridine, bpyO = deprotonated 2,2′-bipyridine N-oxide, and ppy = deprotonated 2-phenylpyridine), were evaluated against human lung (A549), ovarian (SKOV3) and breast (MCF-7) cancer cell lines. The most cytotoxic compounds, 2a, 2c and 2d, effectively produced cell death by inducing apoptosis in the A549, SKOV3 and MCF-7 cancer cell lines. In addition, the molecular docking simulation was performed to determine the specific binding mode and the orientation of binding to DNA. According to the results of biological evaluation, the dppf-containing cycloplatinated(ii) complexes exhibited strong interactions with DNA as well as high cytotoxicity and apoptosis-inducing activities to human cancer cell line. The present study suggests that precise rational design of new platinum-based complexes would result in the preparation of potential anticancer drugs, which can induce facile apoptosis. [ABSTRACT FROM AUTHOR]

Dichloroacetate (DCA) as a mitochondria-targeting small molecule, through inhibition of pyruvate dehydrogenase kinases (PDK 1-4), promotes mitochondria-regulated apoptosis and hence, inhibits tumour growth and reduces its proliferation. In this study, a series of novel N-aryl-2,2-dichloroacetamide and aryl-2,2-dichloroacetate derivatives were designed and synthesized. Their cytotoxic activities against various human cancer cell lines including A549, HCA-7, MCF-7, MDA-MB-231, KB and SKOV3 were evaluated. These compounds showed satisfactory potencies with much higher anticancer activity than the parent compound DCA, against the studied cancer cell lines. Molecular docking studies were also done to find their binding site and types of their interactions with PDKs isoenzymes. Among the synthesized compounds, 2,2-dichloro-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)acetamide (f1) can also induce A549 cells apoptosis. Therefore, compound f1 might have a potential value for further study in drug development. QSAR studies of this class of compounds were also explored using a collection of chemometrics methods. A series of novel N-aryl-2,2-dichloroacetamide and aryl-2,2-dichloroacetate derivatives were designed and synthesized. Their cytotoxic activities against various human cancer cell lines including A549, HCA-7, MCF-7, MDA-MB-231, KB and SKOV3 were evaluated.Apoptosis, Molecular docking and QSAR studies of them were also explored. Image 1 • Design and synthesis of novel N-aryl-2,2-dichloroacetamide and aryl-2,2-dichloroacetate derivatives. • Compounds showed good cytotoxic activities against various human cancer cell lines. • Finding compound f1 for further study in drug development. • Well accommodation of the synthesized compounds in docking studies on pyruvate dehydrogenase kinases (PDKs) isoenzymes. • 2D-QSAR studies to make relations between structural characteristics and cytotoxic activities of the synthesized compounds. [ABSTRACT FROM AUTHOR]