Isoindigo and azaisoindigo: synthesis, characterization, preparation of functionalized analogues and evaluation of their biological activity against SARS-Cov-2
Isoindigos; azaisoindigos; organic synthesis; SARS-CoV-2.
This doctoral thesis for the Graduate Course in Chemistry is an approach of the synthesis of heterocyclic substances such as derivatives of isoindigo and azaisoindigo with potential biological activity against SARS-CoV-2. The work was divided into three main parts: the first consisted in synthesizing new acetylated and disubstituted compounds of 3-hydroxy-bis-oxindoles and isoindigos via coupling methodologies according to the literature. The corresponding isatin derivatives were synthesized by coupling conditions with ZrCl4/EtOH/reflux or with HCl/AcOH/reflux, the use of oxindole and functionalized isatins, obtaining 3-hydroxy-bis-oxindoles as products, which were later dehydrated into isoindigos. The second part, in turn, was the synthesis of azaisoindigos, derived from synthetic methodologies for the coupling between isatin derivatives and 7-azaoxoindole. And finally, the third part encompassed the reduction reactions of isatin and its derivatives with NaBH4. A large part of the substances synthesized in this thesis were submitted to biological tests against SARS-Cov-2 through the assay with Vero E6 cells in a High Content Screening platform, carried out by Professor Dr. Lúcio Freitas Júnior from the Biological Sciences Institute, University of São Paulo (ICB -USP). These compounds were tested with single concentration of 10µM, using chloroquine as control. Preliminary results indicated that 06 compounds (4 isatin derivatives and 2 azaisoindigo derivatives) showed biological activity against this virus, responsible for the transmission and manifestation the symptoms of Covid-19. The results, discussions about these experiments, beyond any characterization of the products obtained from analytical techniques such NMR 1H and 13C, FTIR, HRMS, melting point and biological tests will be taken in the course of this work.