Synthesis, characterisation and cytotoxicity of platinum(II) complexes containing natural ligands with biological activity

Cancer always is among the major causes of death worldwide and only limited progresses were carried onto in order to reduce its morbidity and mortality. Starting from its approval in 1979, cisplatin became probably the most important component of chemotherapy for treating the ovarian, testicular, lung and bladder carcinomas, as well as lymphomas, myelomas and melanoma. Although, cisplatin is a widely used anticancer drug, its clinical exploitation leads to several side effects (decline of kidney, tubular and marrow cells, auditory system). Moreover, several cancer cells are not or poorly sensitive to the cis-Pt action. As a consequence, the recognition of suitable alternatives able to reduce of side effects during the anticancer therapy, some researches were carried out for providing other cis-Pt type complexes free from these contraindications. Therefore, several hundreds of cisplatin analogues were tested during the last 20 years, and many of these species were rejected in preclinical or early clinical stages of testing. Then, the development of more selective and less toxic Pt-based drugs than cisplatin is still highly desirable. Recently, the anticancer activity of naturally occurring substances obtained from plants, such as flavonoids, curcumin and caffeine, has been tested and about 20 new drugs derived from natural products were introduced from 2001 to 2005. So, a lack of knowledge also occurs about the possibility to combine the anticancer capability of cis-Pt related complexes with the limited contraindications for the human health given by the exposure to substances obtained from plants. This study is focused on the scope to fill this gap providing information about the cytotoxic activity of cis-Pt type complexes synthetized using ligands extracted from natural substances obtained from plants. The research was carried out according two different paths. Firstly, these new complexes were synthetized, characterized according spectroscopic investigations and then their cytotoxic activity assessed towards several cancer cell lines in terms of IC50 values. As follows, further investigations were carried out in order to provide information about the extent of interactions between DNA and the new synthetized Pt-complexes with curcumin and caffeine, that were obtaining through different characterization techniques. Our results suggest that the exploited metal complexes act as efficient DNA binders. Suitable crystals for XRD analyses were also obtained for some of the synthesized complexes.