Synthesis, structure, biochemical, and docking studies of a new dinitrosyl iron complex [Fe2(μ-SC4H3SCH2)2(NO)4]

• Two new binuclear DNICs were structurally characterized.
• Complexes can inhibit the action of active site cysteine proteins.
• Biological activity of DNICs is the function of μ-SR bridging ligand structure.

A new dinitrosyl iron complex of binuclear structure [Fe2(μ-S-2-methylthiophene)2(NO)4] was first synthesized and structurally characterized by XRD and theoretical methods. Using caspase-3 as an example it was shown that [Fe2(μ-S-2-methylthiophene)2(NO)4] and its analog [Fe2(μ-S-2-methylfurane)2(NO)4] can inhibit the action of active site cysteine proteins; the difference in inhibitory activity was explained by molecular docking studies. Biochemical and in silico studies give grounds that the biological activity of dinitrosyl iron complexes is a μ-SR bridging ligand structure function.Thus the rational design strategy of [Fe2(μ-SR)2(NO)4] complexes can be applied to make NO prodrugs with high affinity to therapeutically significant targets involved in cancer and inflammation.

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