Carboxymethyl Chitosan/Sodium Alginate/Chitosan Quaternary Ammonium Salt Composite Hydrogel Supported 3J for the Treatment of Oral Ulcer.

Oral ulcer is a common inflammatory disease of oral mucosa, causing severe burning pain and great inconvenience to daily life. In this study, compound 3J with anti-inflammatory activity was synthesized beforehand. Following that, an intelligent composite hydrogel supported 3J was designed with sodium alginate, carboxymethyl chitosan, and chitosan quaternary ammonium salt as the skeleton, and its therapeutic effect on the rat oral ulcer model was investigated. The results show that the composite hydrogel has a dense honeycomb structure, which is conducive to drug loading and wound ventilation, and has biodegradability. It has certain antibacterial effects and good anti-inflammatory activity. When loaded with 3J, it reduced levels of TNF-α and IL-6 in inflammatory cells by up to 50.0%. It has excellent swelling and water retention properties, with a swelling rate of up to 765.0% in a pH 8.5 environment. The existence of a large number of quaternary ammonium groups, carboxyl groups, and hydroxyl groups makes it show obvious differences in swelling in different pH environments, which proves that it has double pH sensitivity. It is beneficial to adapt to the highly dynamic changes of the oral environment. Compared with single hydrogel or drug treatment, the drug-loaded hydrogel has a better effect on the treatment of oral ulcers.

Design, synthesis, and biological evaluation of diaryl heterocyclic derivatives targeting tubulin polymerization with potent anticancer activities.

A series of diaryl heterocyclic analogues were designed and synthesized as tubulin polymerization inhibitors. Among them, compound 6y showed the highest antiproliferative activity against HCT-116 colon cancer cell line with an IC50 values of 2.65 µM. Compound 6y also effectively inhibited tubulin polymerization in vitro (IC50 of 10.9 µM), and induced HCT-116 cell cycle arrest in G2/M phase. In addition, compound 6y exhibited high metabolic stability on human liver microsomes (T1/2 = 106.2 min). Finally, 6y was also effective in suppressing tumor growth in a HCT-116 mouse colon model without apparent toxicity. Collectively, these results suggest that 6y represents a new class of tubulin inhibitors deserving further investigation.