Synthesis and characterization of a spiroindolone pyrothiazole analog via X-ray, biological, and computational studies

Synthetic and natural spiroxindoles are important anti-inflammatory, antibacterial, antileishmanial, and anticancer agents. In this study, we prepared a spiroxindole derivative and evaluated the preliminary results of its biological activity including anti-inflammatory, antileishmanial, and cytotoxic activity against 3T3 and Hela cell lines. By adopting the 1,3-dipolar cycloaddition reaction, we were able to successfully combine olefin, isatin, and an amino acid to form the desired spiroxindole analog 4 (yield, up to 94%). To elucidate the chemical structure of 4, the X-ray single crystal diffraction technique was employed, and the electronic and NMR spectra of 4 were calculated using the B3LYP/6-311G(d,p) method. The calculated H-1 and C-13 NMR chemical shifts aligned well with the experimental data. Compound 4 was then evaluated for its anti-inflammatory, antileishmanial, and cytotoxic activity against 3T3 and Hela cell lines. This spiroxindole pyrothiazole (IC50 = 65.9 +/- 6.6 mu M) showed weak anti-inflammatory activity compared to the test standard, ibuprofen (IC50 = 11.2 +/- 1.9 mu M), and moderate anticancer activity against Hela cell lines compared to doxorubicin (IC50 = 1.2 0.4 mu M vs IC50 = 11.2 +/- 0.3 mu M for 4). Compound 4 also appeared as an effective antileishmanial agent (IC50 = 39.8 0.43 mu M) when tested in vitro. (C) 2019 Elsevier B.V. All rights reserved.