5D-QSAR studies of 1H-pyrazole derivatives as EGFR inhibitors.

Epidermal growth factor receptor (EGFR) is highlighted as a target for anticancer treatment. Several EGFR inhibitors were approved in cancer treatment. Comparatively, 5D-QSAR is a new methodology which considers an ensemble of different induced-fit models. Based on 1H-pyrazole derivatives as EGFR inhibitors, a 5D-QSAR was studied in which the method of quasi-atomistic receptor surface modeling was used. The presented QSAR model showed contributions of the hydrogen bond acceptor, and hydrophobic and salt bridge fields to the activity. The QSAR model was statistically validated and also externally validated applying 19 compounds (test set) which were not included in the model generation process. The scramble tests were performed to further verify the robustness. Apart from exploration of the binding of 1H-pyrazole derivatives to the EGFR, the 5D-QSAR model can be helpful to design of new EGFR inhibitors. The five-dimensional quantitative structure-activity relationship (5D-QSAR) of 1H-pyrazole derivatives as EGFR inhibitors with quasi-atomistic receptor surface modeling approach is described.

An injectable and self-healing hydrogel with antibacterial and angiogenic properties for diabetic wound healing.

The treatment of diabetic wounds remains a global challenge. Compared with traditional wound dressings, there are higher requirements of antibacterial, anti-inflammatory and pro-angiogenic effects in diabetic wound dressings. Furthermore, it is desirable for dressings to self-adapt to wounds with different morphologies without extra processes and stably (suitable adhesive and self-healing abilities) provide a conducive environment for wound healing. Herein, we construct an injectable and self-healing hydrogel through the combination of chitosan (CS) and metal ions to efficiently improve infected and diabetic wound healing. Benefiting from the amino and hydroxy groups, the CS molecular chains are cross-linked with silver ions (Ag+) and copper ions (Cu2+) to promote the formation of the CS-Ag-Cu hydrogel, which releases Ag+ (an antibacterial agent) and Cu2+ (an angiogenic agent) over a prolonged period. Moreover, the hydrogel possesses appropriate adhesive ability, good water absorption ability, antibacterial capability and biocompatibility according to in vitro investigations. In vivo experimental results further prove that the CS-Ag-Cu hydrogel can dramatically accelerate tissue repair in a Staphylococcus aureus (S. aureus)-infected skin incision model in normal rats and diabetic wounds.