Potent antiproliferative active agents: novel bis Schiff bases and bis spiro β-lactams bearing isatin tethered with butylene and phenylene as spacer and DNA/BSA binding behavior as well as studying molecular docking

AbstractA [2+2]-cycloaddition of bis-isatin Schiff bases5a –b and7 with activated aryloxyacetic acid derivatives8a –d afforded bis-spiroisatino β-lactams with aliphatic and aromatic spacers. The structures of the synthesized 2-oxindoles and spirooxindoles were determined based on Fourier-transform infrared spectroscopy, proton-1 and carbon-13 nuclear magnetic resonance spectroscopies and CHN analysis. Our interest in these bis-Schiff bases and bis-spiroisatino β-lactams is for their potential anticancer capabilities. In vitro bioactivity testing against the cervical adenocarcinoma (HeLa) and breast cancer (MCF-7) cell lines as well as noncancerous NIH/3T3 fibroblast cell was investigated applying the MTT assay. Bis-isatin derivative s5a,5b,9h,10a, and10b showed promising antiproliferative activity toward these two cancer cell lines. Two of the bis-isatin Schiff bases,5a and5b, displayed IC50 values less than that of the clinically-used anticancer agent cisplatin towards both the MCF-7 and HeLa cells, while several of the bis-isatin β-lactams showed similar bioactivity to that of cisplatin. All of the oxindoles and spirooxindoles displayed a selective anticancer effect except10b. To study the possible mechanism for this bioactivity, DNA and BSA binding analyses were performed using fluorescence and UV –visible spectroscopic techniques. The isatin adducts displayed excellent interaction propensity to CT-DNA as well as BSA. Molecular docking investigation carried out on...
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research