Towards Identifying Potent New Hits for Glioblastoma

Glioblastoma is a devastating disease of the brain and is the most common malignant primary brain tumour in adults. The prognosis for patients is very poor with median time of survival after diagnosis measured in months, due in part to the tumours being highly aggressive and often resistant to chemotherapies. Alongside the ongoing research to identify key factors involved in tumour progression in glioblastoma, medicinal chemistry approaches must also be used in order to rapidly establish new and better treatments for brain tumour patients. Using a computational similarity search of the ZINC database, alongside traditional analogue design by medicinal chemistry intuition to improve the breadth of chemical space under consideration, six new hit compounds (14, 16, 18, 19, 20 and 22) were identified possessing low micromolar activity against both established cell lines (U87MG and U251MG) and patient-derived cell cultures (IN1472, IN1528 and IN1760). Each of these scaffolds provides a new platform for future Page 1 of 29 MedChemComm development of a new therapy in this area, with particular promise shown against glioblastoma subtypes that are resistant to conventional chemotherapeutic agents

Novel Trolox derivatives as antioxidant: A DFT investigation

In this paper the antioxidant activity of Trolox derivatives were investigated by density function theory and polarization continuum model as solvent model in order to propose the novel derivatives with higher antioxidant activity from a theoretical viewpoint. The effects of various ortho and meta substituents on the reaction enthalpies of antioxidant mechanisms of Trolox were investigated. Also the effect of reducing the number of atoms in the heterocyclic ring and effect of replacing the oxygen heteroatom of Trolox with other heteroatoms on the antioxidant activity of Trolox were evaluated. Results show that the NH2, OH and NHMe substituents in meta and ortho positions decrease the BDE and IP values and also increase the antioxidant activity of Trolox from the theoretical viewpoint. The derivatives e, c and d with NH, S and Se instead of O have higher antioxidant activity from the theoretical viewpoint. Obtained results show that reducing the number of atom in the heterocyclic ring (derivatives a and b) decrease the BDE and IP values and also increase the antioxidant activity of Trolox from the theoretical viewpoint. The linear dependencies between BDE of OH bond and IP values of studied Trolox derivatives and corresponding EHOMO and R(O-H) values can be useful to propose novel derivatives with higher antioxidant activity from the theoretical viewpoint

Effect of oxygen termination on the interaction of first row transition metals with M2C MXenes and the feasibility of single-atom catalysts

A density functional theory-based study was performed to investigate the stability of single-atom catalysts (SACs) over a series of O-terminated MXenes with the stoichiometry of M2CO2. Accordingly, we selected the first-row transition metals as adatoms and nine MXene surfaces as supports. From a thermodynamic viewpoint, the stability of the resulting SACs is favorable for all combinations between adatoms and MXenes. However, the adatoms tend to cluster together to a rather low energy barrier, promoting diffusion, which significantly affects their stability. The present systematic study showed that Sc@ and Ti@M2CO2 are the most feasible SACs because of their high metal-support interaction, low tendency to form metal clusters and high diffusion barriers. The present results can be useful to experimentalists aimed at synthesizing SACs based on MXenes