Clotrimazole

The anti‑leishmanial activity of the ruthenium‑clotrimazole complex AM162 was evaluated in a murine model of cutaneous leishmaniasis, along with its mechanism of action against Leishmania major promastigotes. AM162 significantly reduced lesion size in infected mice. Mechanistically, the complex induced a mitochondrial‑dependent apoptotic‑like death in parasites, characterized by DNA fragmentation, mitochondrial depolarization, cell cycle alteration, and plasma membrane phospholipid externalization. The authors conclude that AM162 shows promise for treating cutaneous leishmaniasis by inducing parasite apoptosis, warranting further preclinical evaluation and therapeutic development.

Fig. 1 Ru-CTZ complexes induced phospholipids externalization in L. major promastigotes after 24 h of treatment at 2 μM. (Iniguez E, et al., 2016)

This study identified the antifungal drug clotrimazole as an enhancer of dendritic cell (DC)-mediated antigen presentation through screening of FDA-approved drugs. Clotrimazole acted on hexokinase 2 to regulate lactate metabolic production, which enhanced lysosome pathway function and CHOP expression, subsequently inducing DC maturation and T cell activation. In vivo, clotrimazole administration induced intratumor immune infiltration, inhibited tumor growth in a DC- and CD8+ T cell-dependent manner, and potentiated anti-PD1 antibody efficacy. The authors conclude that clotrimazole triggers DC activation via the lactate-lysosome axis and represents a potential combination partner for cancer immunotherapy.

Fig. 2 Clotrimazole enhanced DC-induced T cell activation. (Wang Z, et al., 2021)