0000000000527372
AUTHOR
A. M. Almerico
CHA on CDK2: a way to identify the best pharmacophore model for the virtual screening of new inhibitors
Cyclin-dependent kinase-2 (CDK2) is a member of serine/threonine protein kinases family. It plays an important role in the regulation events of the eukaryotic cell division cycle, especially during the G1 to S phase transition. Experimental evidences indicate that excessive expression of CDK2 should cause abnormal cell cycle regulation. Therefore, CDK2 has been considered a potential therapeutic target for cancer therapy. In this work, we used a modelling approach that incorporates flexibility based on extensive MD simulations of protein−ligand complexes into structure-based pharmacophore modeling and virtual screening to identify new CDK2 inhibitors. One-hundred and forty-nine CDK2-inhibit…
Consensus modelling and molecular dynamics studies for the identification of novel telomerase inhibitors as anti-cancer agents
Telomerase plays an important role in early stages of life-maintaing telomere and chromosomal integrity of frequently dividing cells. It turns dormant in most somatic cells during adulthood. However, in cancer cells, telomerase gets reactivated and works tirelessly to maintain the length of telomeres, leading to immortality of cells. Hence, in this study, we have used a combined ligand-based and structure based drug design approach for the identification of novel telomerase inhibitors as anti-cancer agents. We have generated ligand-based QSAR models and structure-based pharmacophores models, according our recent MYSHAPE approach (1), and validated exhaustively. The validated models were use…
Natural bioactive molecules induce a reduction of surface alpha-enolase in breast cancer cells
Cell surface expression of alpha-enolase, a glycolytic enzyme displaying moonlighting activities, has been shown to contribute to cancer cell invasion and metastasis formation. Although the functional role of surface alpha-enolase in cancer spreading has been clearly linked to the protein non-enzymatic function of binding plasminogen and enhancing plasmin formation, the cellular pathways underlying cell surface transport remain largely elusive. We have previously demonstrated that pro-invasive stimuli promote the surface expression of alpha-enolase in breast cancer cells. To further investigate alpha-enolase translocation to the plasma membrane and to identify the signaling involved in this…
Synthesis and antiproliferative activity of [1,2,4] triazino[4,3-a]indoles
A series of [1, 2, 4triazino[4,3-a]indoles was prepared in good yield by reacting 2-diazo-3-ethoxycarbonylindole with methylene active compounds. Derivatives of the title ring system were tested against a panel of 60 human tumor cell lines, and showed inhibitory activity against a wide range of cancer cell lines at micromolar concentration.