Evaluation of Anticancer Activity of 1,3‐Oxazol‐4‐ylphosphonium Salts in Vitro

A novel series of 1,3‐oxazol‐4‐yltriphenylphosphonium salts has been synthesized and functionalized. Oxazole derivatives were subjected to NCI in vitro assessment. Seven most active derivatives have been selected for five‐dose assay. Among them, compounds 9 ([2‐(4‐methylphenyl)‐5‐[(4‐methylphenyl)sulfanyl]‐1,3‐oxazol‐4‐yl]triphenylphosphonium perchlorate), 1 ([5‐(4‐methylphenyl)amino]‐2‐phenyl‐1,3‐oxazol‐4‐yl]triphenylphosphonium perchlorate) and 4 ([5‐phenyl‐2‐[(4‐methylphenyl)amino]‐1,3‐oxazol‐4‐yl]triphenylphosphonium perchlorate) were the most active against all tested cancer subpanels. Statistical analysis of the total panel data showed average values of parameters of anticancer activity in the range of 0.3–1.1 μM (GI(50)), 1.2–2.5 μM (TGI) and 5–6 μM (LC(50)). It was found that the presence of phenyl or 4‐methylphenyl groups at C(2) and C(5) in the oxazole ring is of critical importance for the manifestation of the anticancer activity. Matrix COMPARE analysis using LC(50) vector showed a high positive correlation of compound 9 with standard anticancer agents that can directly disrupt mitochondrial function, causing programmed death of cancer cells. The obtained results indicate the anticancer activity of 1,3‐oxazol‐4‐ylphosphonium salts, which could be useful for developing new anticancer drugs. The most active of them can be recommended for further in‐depth studies and synthesis of new derivatives with antitumor activity on their basis.