Diarylation of thiazolopyrimidines by laccase and their in vitro evaluation as antitumor agents

Abstract

A mild and efficient method was developed for the synthesis of new derivatives of thiazolo[3,2-a] pyrimidin-3(2H)-ones from available starting materials based on the oxidation of catechols to ortho-quinone by Myceliophthora thermophila laccase (Novozym 51,003) and 1,4-addition of active methylene carbon to these in situ generated intermediates in moderate to good yields (35–93%). The structure of the products was confirmed through 1H NMR, 13C NMR, HMBC, HSQC, DEPT-135, and mass spectroscopy techniques. These novel compounds were evaluated as active antitumor agents against human colorectal adenocarcinoma and liver adenocarcinoma cell lines. All compounds displayed potent inhibition activities against the HT-29 cell line with IC50 values of 9.8–35.9 µM, superior to the positive control doxorubicin, and most showed potent anticancer activities against the HepG2 cell line.

Biocatalytic Synthesis of Nitrile-Bearing All-Carbon Quaternary Stereocenters

“…Syntheses of aminoquinones 68 and morpholine derivatives with M. thermophila laccase as a catalyst are some examples. 69 Following the previous works in our lab with laccase in the synthesis of organic compounds, 70,71 the enzymatic synthesis of all-carbon quaternary stereocenters containing nitrile is presented.…”

“…Following the previous works in our lab with laccase in the synthesis of organic compounds, , the enzymatic synthesis of all-carbon quaternary stereocenters containing nitrile is presented.…”

Biocatalytic stereoselective synthesis of pyrrolidine-2,3-diones containing all-carbon quaternary stereocenters

“…The synthesis of organic compounds using biocatalysts, especially enzymes, has received much attention in recent decades. [36][37][38][39][40] Laccases (E.C.1.10.3.2. ), which belong to the category of oxidoreductase enzymes, catalyze the one-electron oxidation of a substrate (through the T1 copper ions) and transfer the electrons by two T3 copper ions to one T2 copper ion for the reduction of molecular oxygen to water.…”