Synthesis and evaluation of Carbohydrate containing Bioconjugates of Carborane for cancer therapy

Abstract

It is well known that successful treatment of cancer is still a worldwide challenge for the researchers. There are many cancer treating methods such as surgery, chemotherapy, radiation, palliative care, immunotherapy, alternative medicines, laser therapy, etc are developed till today, but none of the method is fully efficient in treating cancer because of their limitations to use. The chemotherapeutic method that used mostly also limits its effectiveness due to its toxicity to other healthy cells in the body. This dissertation work is based on the hydrophobic ortho-carborane cluster, which is enriched with ten boron atoms, two carbon atoms and a number of hydrogens. The boron atoms and the carbons are connected to each other in such a way that they form a cage-like structure, each connected to at least one hydrogen atom, if not functionalized. Here also carbohydrates such as glucose and/or galactose were linked to the hydrophobic ortho-carborane moiety to make them water soluble for biocompatibility and as a carrier for selective incorporation of the boron atoms to the tumor tissue as they have strong affinity towards different receptor proteins found on the surface of the tumor cell. The focus of the thesis was to develop a multi-step organic synthetic methodology to synthesize tumor targeted water soluble new boron drug delivery agent by attaching ortho-carborane with carbohydrate (Galactose and/or Glucose) derivatives. The carborane-carbohydrate glycoconjugates could act as anticancer therapeutics or selectively deliver a sufficient amount of boron drug within tumor cells with least toxicity and treat different types of cancer via cytotoxic BNCT (boron neutron capture therapy) without hampering the normal healthy cells in the body. The 1st chapter of the thesis introduces the symptoms, causes and management of cancer. Herein, it summarizes the general characteristics, structure, synthetic methods and characterization techniques used for the icosahedral carborane clusters.