Small molecule inhibitors targeting DNA repair pathways in cancer cells is a novel and promising approach in cancer therapy, which can improve current therapeutic regimen. Although various attempts have been made for designing inhibitors against DNA damage response and repair proteins, reports on Nonhomologous End Joining (NHEJ) inhibitors are limited. Of the several chemical moieties identified, SCR7 and its oxidized form are novel and potent DNA Ligase IV inhibitors involved in the abrogation of DNA end joining thereby leading to cell death. In the present study, we have synthesized sodium salt of SCR7 to generate a water-soluble version of the molecule, referred to as water-soluble SCR7 (WS-SCR7). WS-SCR7 inhibits NHEJ in Ligase IV dependent manner, with a subtle effect on Ligase III at higher concentration. No effect on Ligase I mediated joining was observed. WS-SCR7 shows cytotoxicity in cancer cell lines, leading to induction of apoptosis in a dose-dependent manner.

C(3)-Aminoisoindolinones have attracted the attention of medicinal chemists due to their unique and stable NÀ CÀ N substructure and possibilities for facile and scalable synthesis of combinatorial libraries. We discovered that para-toluenesulfonic acid (PTSA), an organic protic acid, efficiently catalyzes condensation of isoindolinone-3-ols with primary and secondary amines to furnish C(3) N-substituted isoindolinones in high yields. The NÀ C bond formation reaction is highly efficient and experimentally simple. The method replaces known transition metal catalysts involving Cu, Pt, Pd or Au. It works efficiently for both intra-and inter-molecular variants. Furthermore, it is amenable for synthesis of C(3)-aminoisoindolinones with free N(2) via photolytic deprotection of the 2-nitrobenzyl group. We have demonstrated application of the method for synthesis of a variety of medicinally relevant bicyclic and tricyclic C(3)-aminoisoindolinones.