About the seminar:

Thiosemicarbazone complexes have been synthesized and studied for well over 50 years. More recently, thiosemicarbazones have been studied and investigated for their therapeutic potential and have shown to have anti-cancer,1,2 anti-bacterial,3 and anti-microbial effects.4 Several potential therapeutics have been studied both in vitro and in vivo,5 with a recent example being the drug Triapine. This investigational drug has undergone several FDA clinical trials with varying successes.6,7 The greatest advantage thiosemicarbazones demonstrate as potential therapeutic target are an easily modifiable structure at several different positions. This allows for facile and simple modifications to enhance efficacy, selectivity, hydrophilicity, or lipophilicity depending on the drug target. Thiosemicarbazones are typically synthesized as the condensation product between Thiosemicarbazide with an aldehyde or ketone to form an imine complex, most commonly from from a salicylidene or pyridine moiety.3,4,6 However, these structural motifs can limit the scope of derivatization to aromatic Schiff bases, which means new approaches to thiosemicarbazone derivatives with alkyl moieties are of high interest.

The diversity of commercially available sugars, such as glucose, fructose, and ribose, makes them a desirable moiety to create a complex molecular library of thiosemicarbazones, with a synthetic pathway to these complexes shown in Figure 1. Along with the diversity of sugars through stereochemistry and can be readily functionalized (an example being an amino sugar), sugars and other carbohydrates are well-known for their innate therapeutic potential.8 These derivations allow for the synthesis of novel thiosemicarbazone complexes with a sugar moiety in relatively low steps and in appreciable yields with several potential pathways to create an extensive molecular library. By attaching sugar moieties to thiosemicarbazones, an increase in both aqueous solubility and increased biological activity is expected.

While thiosemicarbazones have seen success as potential anticancer therapeutics, there are several concerns with the side effects that were present for clinical trials for Triapine and other thiosemicarbazone derivatives.6,7 Recent studies have proven that chelation of these ligands to metals like copper not only lead to having prolific anticancer properties but help mitigate the adverse side effects of the drug.9 With these results in mind, the synthesis and study of thiosemicarbazone complexes as both organic and metal-based anticancer therapeutics to compare their physical properties and capability as anticancer therapeutics should be investigated. It is expected that sugar-modified thiosemicarbazones will exhibit improved solubility, enhance anticancer activity compared to traditional thiosemicarbazone scaffolds, and coordination to biologically relevant metals (such as copper) will further increase therapeutic efficacy and potentially reduce off-target toxicity seen previously in thiosemicarbazone complexes.