Chlorambucil-Asparagine, a Novel Chemotherapeutic Agent

4 Abstract: As cancer disease has become a significant health issue all over the world, it is important to increase the effectiveness of anti cancer drugs and reduce their adverse side effects. A number of anti cancer drugs have been discovered so far, one of which is known as Chlorambucil. It is a member of Alkylating drugs that attack DNA of cancerous cells and kill them. Great numbers of conjugates have been designed in order to make Chlorambucil more effective and less harmful. A couple of reports have suggested that accumulation and uptake of Polyamine compounds and amino acid transporters increase in cancer tissues. Therefore, we connected an amine amino acid (Asparagine) to Chlorambucil in order to create a novel and efficient anti cancer conjugate. After purifying our product and performing some quality control tests, its anti cancer effects on HT1080 cell line were evaluated. MTT, apoptosis, necrosis and abnormality tests were conducted to check its toxic properties. Finally, it was evaluated if Chlorambucil affects blood hemolysis rate and blood clotting factors or not. It was observed that not only dose Chlorambucil-Asparagine conjugate has anti cancer property, but also it is capable of killing the half of the cancerous cells in lower concentrations compared to Chlorambucil. So, using lower dose of a drug can help reducing its undesirable side effects. Besides, the new drug has no effect on normal growth of Sprague Dawley rats. Also, it is not caused blood hemolysis and does not change the clotting factors. Moreover, it is determined that it can kill cells by mechanism of inducing apoptosis. In conclusion, a new, more efficient, cancer targeted version of an anti cancer drug was synthesized successfully in this study. The results indicate that Chlorambucil-Asparagine conjugate seems to have a bright future for further studies and treatment of cancer.