Applying molecular hybridization to design a new class of pyrazolo[3,4-d]pyrimidines as Src inhibitors active in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver solid tumor and the second leading cause of cancer-related deaths worldwide. Although new treatment options have been recently approved, the development of tumor resistance and the poor prognosis for advanced HCC make the current standard of care unsatisfying. In this scenario, the non-receptor tyrosine kinase (TK) c-Src emerged as a promising target for developing new anti-HCC agents.

Cooperative chemoenzymatic and biocatalytic cascades to access chiral sulfur compounds bearing C(sp)-S stereocentres.

Biocatalysis has been widely employed for the generation of carbon-carbon/heteroatom stereocentres, yet its application in chiral C(sp)-S bond construction is rare and limited to enzymatic kinetic resolutions. Herein, we describe the enantioselective construction of chiral C(sp)-S bonds through ene-reductase biocatalyzed conjugate reduction of prochiral vinyl sulfides. A series of cooperative sequential/concurrent chemoenzymatic and biocatalytic cascades have been developed to access a broad range of chiral sulfides, including valuable β-hydroxysulfides bearing two adjacent C(sp)-S and C(sp)-O stereocentres, in a stereoconvergent manner with good to excellent yields (up to 96%) and enantioselectivities (up to >99% ee).

Benzenesulfonamide decorated dihydropyrimidin(thi)ones: carbonic anhydrase profiling and antiproliferative activity.

In the last decades, carbonic anhydrases (CAs) have become the top investigated innovative pharmacological targets and, in particular, isoforms IX and XII have been widely studied due to the evidence of their overexpression in hypoxic tumors. The frantic race to find new anticancer agents places the quick preparation of large libraries of putative bioactive compounds as the basis of a successful drug discovery and development programme. In this context, multi-component and, in general, one-step reactions are becoming very popular and, among them, Biginelli's reaction gave clean and easy-to-isolate products.

A tripartite organelle platform links growth factor receptor signaling to mitochondrial metabolism.

One open question in the biology of growth factor receptors is how a quantitative input (i.e., ligand concentration) is decoded by the cell to produce specific response(s).