Identification of CYP3A4 inhibitors as potential anti-cancer agents using pharmacoinformatics approach.

Biguanide derivatives exhibit a wide variety of therapeutic applications, including anti-cancer effects. Metformin is an effective anti-cancer agent against breast cancer, lung cancer, and prostate cancer. In the crystal structure (PDB ID: 5G5J), it was found that metformin is found in the active site of CYP3A4, and the associated anti-cancer effect was explored. Taking clues from this work, pharmacoinformatics research has been carried out on a series of known and virtual biguanide, guanylthiourea (GTU), and nitreone derivatives. This exercise led to the identification of more than 100 species that exhibit greater binding affinity toward CYP3A4 in comparison to that of metformin. Selected six molecules were subjected to molecular dynamics simulations, and the results are presented in this work.

Quantum chemical study in exploring the role of donor→acceptor interactions in 1,3-bis carbene-stabilized guanidinium cations.

Guanidinium species are highly basic and hence mostly exist in cationic state. Because these cations carry electron-deficient centers, they can be stabilized with the help of electron-donating ligands like N-heterocyclic carbenes. A few novel guanidinium cationic species stabilized by electron-donating ligands were designed and quantum chemically evaluated. It was shown that strong hydrogen bonds and tautomerism are the important characteristics of these species. Further, the possibility of donor→acceptor coordination interactions in these species have been explored between the electron-donating carbenes and the central guanidinium unit. The results suggest that the title compounds can be considered as ligand-stabilized guanidinium cations similar to the ligand-stabilized N+ and N3+ centers.