Synthesis, Characterization, and Antioxidant Activities of N-(Diphenylmethyene) hydrazine carbothiohydrazide a new Schiff Bases Derived from Substituted benzophenones and their Complexes

The use of metals for medicinal purposes has been exploited since very ancient times; for instance, silver has been used as a disinfectant agent for water and milk for thousands of years 1 Similarly, the application of gold in medicine can be dated back to 2500 BC and throughout the entire history of humanity it is possible to find traces of several applications of this noble metal to treat various diseases 2 .Indeed, in the 19th century the complex dicyanoaurate(I) (K[Au(CN) 2 ]) was proposed by Koch for its bacteriostatic properties to fight tubercle bacillus, while in the 20th century, gold complexes were introduced to treat rheumatoid arthritis, leading to the approval of Auranofin by FDA in 1985.This latter compound is today the reference compound for gold complexes and, on the ground of the so-called repurposing strategy, has been proposed as promising anticancer agent and entered several clinical trials in US, some of which are still ongoing 3,4 .Beyond silver and gold, several bismuth, antimony and mercury compounds have been employed to combat bacterial and parasitic diseases.In this view, bismuth salts and antimony complexes have been proposed and used for eradication of Helicobacter pylori infection, and against leishmaniasis respectively 5 .Also, arsenic, in the form of trioxide (As 2 O 3 ), is nowadays one of the reference drugs for the treatment of acute promyelocytic leukemia 6 .Several inorganic complexes are also used for diagnostic medicine as in the case of gadolinium-based contrast agents, 99m Tc compounds for myocardial perfusion imaging 7 and 64 Cu for PET imaging 8 .However, the most important impulse to the research of metal-based drugs with medicinal properties came from the serendipitous discovery of the antitumor features of cisplatin by Rosenberg and Loretta Van Camp in 1965 9 .Cisplatin was approved in 1978 by the FDA, and this event triggered enormous efforts by scientists in search of innovative and ameliorated inorganic anticancer drugs, leading to the approval worldwide of carboplatin and oxaliplatin analogs.This makes platinum-based drugs an essential arsenal for first-and second-line anticancer chemotherapy used in about 50% of clinical protocols 10 .Metals complexes offer an extremely versatile and reliable tool for the development of improved medicinal compounds.Indeed, it is possible to finely tune the chemical properties of these complexes by controlling the metal center oxidation state and selecting the most appropriate ligands for each application.Thus, it is not surprising that the challenge in the development of innovative and improved metal-based drugs largely overlaps with the development of innovative and ameliorated ligands for the functional metal element.Among several ligands, thiosemicarbazones (TSCs), are a very attractive class of metal-chelating ligands, able to coordinate many transition metals through the sulfur as well as the azomethinic nitrogen atoms 11 .They can act as N, S-multidentate ligands, and moreover, it is possible to modulate the binding properties/stoichiometries through the insertion of other heteroatoms into the backbone structure (i.e., phenolic or pyridyl moieties).They have a great variety of biological properties, both as free ligands and as metal complexes, and several studies have been published reporting on thiosemicarbazone-based complexes with medicinal applications [12][13][14][15][16][17][18][19][20][21] .Beyond TSCs, in recent years, there has been growing interest in the coordination chemistry of thiocarbohydrazones (TCHs) compounds that share the general formula depicted in Scheme 1a-c and that can be considered the higher homologues of TSCs (Scheme 1d).