Rational Drug Design

**95**

**Chapter 5**

**Abstract**

**1. Introduction**

Cancers

*Abdul Hameed Khan*

The Rational Drug Design to Treat

Professor Ross of London University, England, was using nitrogen mustard to treat cancers by attacking both strands of tumor DNA. As a part of my doctoral thesis, I am to design drugs using aziridine to attack only one strand of DNA. Over the years, I made over 100 dinitrophenyl aziridine derivatives. One of them is dinitrobenzamide (CB1954) which gives a CI of 70, highest toxicity to animal tumor ever recorded. CB1954 wipes out a solid aggressive tumor by attacking a single-strand DNA of Walker carcinoma 256, in rat. My greatest challenge at NCI in USA is to translate the animal work which I did in London University to humans. As radiolabeled methylated quinone crosses the blood-brain barrier in mice, I decided to use quinone moiety as a carrier for aziridine rings to attack glioblastomas, the brain tumor in humans. By attaching two aziridines and two carbamate moieties to quinone, I made AZQ (US Patent 4,146,622). By treating brain cancer with AZQ, we observed that glioblastoma tumor not only stops growing but also starts shrinking.

Literature search showed that AZQ is extensively studied.

projects most rational and most likely to be accomplished.

**Keywords:** drug design, tumor treatment, novel drugs for cancer treatment

Rational drug design is absolutely essential for developing novel drugs for treating any disease, especially cancers. Our Institute, the NIH (National Institutes of Health is an agency of US Government) learned this fact by spending enormous amount of money over the years by testing known and unknown products obtained by synthesis or from plants and animals on a variety of testing tumor systems. The discovery of a handful of drugs by trial and errors at a cost of millions was considered a waste of time and money. In early days, we absorbed the losses because our Institute, located about 10 miles from Washington, DC, is the largest biomedical center in the world. Our annual budget is over 40 billion dollars per year. Over 26 institutes have about 3000 labs where about 21,000 scientists work in 50 buildings. My lab was in the National Cancer Institute (NCI), which is the largest among all institutes and it has a budget of over 5 billion dollars per year. Now, we became more cautious screening drugs. About 20% of our budget is spent in-house and the 80% of our budget is provided to research labs around the world by reviewing their research projects by expert panels called the study sections to approve funds to
