Synthesis and biological evaluation of inducible nitric oxide synthase inhibitors as anticancer agents

Nitric Oxide (NO) is a free radical signalling molecule, involved in different biological processes and produced by nitric oxide synthases (NOS). There are two constitutive NOS (the endothelial and neuronal ones) and an inducible NOS (iNOS).

In tumour biology, NO has a controversial role, since there is evidence that NO can both inhibit and stimulate tumour cell growth. This response depends on tumour type, genetic background, NO levels and sensibility in the target cells. Correlation between iNOS expression and clinical outcome associated to worse prognosis, was evaluated in different types of tumours. Therefore, inhibition of iNOS has been proposed as a targeted therapy in several cancers, including breast cancer and gliomas.

Our research group is involved in the research of new potent and selective iNOS inhibitors, and we have recently collected evidences of their usefulness as antiglioma agents, compromising in vitro proliferation of cancer cells with selectivity with respect to astrocytes, and ameliorating the effects of the standard therapeutic agent temozolomide. Moreover, a set of azole-based compounds showed interesting activity both as iNOS and aromatase inhibitors, compromising the MCF-7 breast cell line proliferation, and thereby suggesting their potential application in a polypharmacological approach. In this presentation results obtained from these studies will be shared.