Triazole-imidazo[1,2-]pyrazoles Able to Counteract Melanoma Cell Survival Without Compromising the Viability of Healthy Keratinocytes.

To further extend the structure-activity relationships on previously identified anti-proliferative imidazo-pyrazoles, a novel series of compounds was designed and synthesized. In the obtained derivatives (), the imidazo-pyrazole scaffold was formally condensed with a substituted triazole moiety, known for its biological properties. All derivatives were tested for anti-proliferative activity on a panel of 60 different cancer cell lines and compound was identified as the most promising derivative, being highly effective against melanoma cells. Additional investigations demonstrated a cytotoxic and pro-oxidant action of the compound on human metastatic melanoma cell lines (MeOV and MeTA) but not on healthy keratinocytes (HaCAT), confirming the selective activity of the compound. In silico calculations predicted favorable drug-like and pharmacokinetic properties and pre-formulation studies evaluated the effect of Tween 80 on solubility. Overall, the collected data confirmed the pharmacological potential of the imidazo-pyrazole scaffold and indicated as an interesting lead structure for the development of novel anti-melanoma agents.