Preclinical Study of Immunological Isoxazole Derivatives as a Potential Support for Melanoma Chemotherapy

Abstract

(1) Background: Melanoma is an aggressive neoplasm derived from melanocyte precursors with a high metastatic potential. Responses to chemotherapy and immunotherapy for melanoma remain weak, underlining the urgent need to develop new therapeutic strategies for the treatment of melanoma. (2) Methods: The viability of NHDF and A375 cell cultures after the administration of the tested isoxazole derivatives was assessed after 24-h and 48-h incubation periods with the test compounds in the MTT test. ROS and NO scavenging analyses, a glycoprotein-P activity analysis, a migration assay, a test of apoptosis, and a multiple-criteria decision analysis were also performed. (3) Results: All compounds that were tested resulted in a slower migration of melanoma neoplastic cells. The mechanism of the antitumor activity of the tested compounds was confirmed—i.e., the pro-apoptotic activity of the compounds in A375 cell cultures. Compound O7K qualified for further research. (4) Conclusions: All the tested compounds inhibited the formation of melanoma metastases and demonstrated the ability to reduce the risk of developing drug resistance in the tumor. The MCDA results showed that O7K showed the strongest antitumor activity.

Isoxazole Derivatives against Carbonic Anhydrase: Synthesis, Molecular Docking, MD Simulations, and Free Energy Calculations Coupled with In Vitro Studies

“…Isoxazole, a heterocycle with an oxygen atom adjacent to a nitrogen atom in a five-membered ring, has garnered considerable attention in recent years due to its versatility and importance in medicinal chemistry. Anticancer, anti-inflammatory, and immunoregulatory actions, as well as AMPA receptor ligand, are only a few of the pharmacological features of derivatives having an isoxazole moiety. − Isoxazole can help compounds interact better with their biological targets in several cases. Isoxazole fragments are also widely used to alter lead compounds for increased efficacy in the realm of anti-tumor drugs.…”