**6. Rationale for developing anticancer drugs**

Nitrogen mustard was mercilessly used during the WWII by both German and Italian armies against allied forces. Most soldiers exposed to nitrogen mustard were frozen to death. Their blood analysis showed a sharp decline in white blood cell (WBC). Since patients with the cancer of the blood called leukemia showed a sharp increase of WBC, Professor Ross and his group wondered if minimum amount of nitrogen mustard could be used to control leukemia in cancer patients. It was a success. For the following 30 years, Ross developed hundreds of derivatives of nitrogen mustard to treat a variety of cancers. His most successful drugs are chlorambucil, melphalan, and merophan [2–6, 14].

Radiolabeled study showed that nitrogen mustard shut off genes by binding to DNA by crosslinking. At London University, I work for Professor Ross for almost 10 years first as his graduate student, then his post-doctoral fellow, and then as his special assistant. I worked with the deadliest nerve agents such as nitrogen mustards, carbamates, and aziridines developed during Hitler's time for evil purposes. We are converting evil into good. These agents easily pass through various layers of our skin from ectoderm to mesoderm to endoderm. They easily enter the cell nucleus destroying the beta and gamma cell which develop immunity. Then they enter the nuclear membrane where they find the stem cells. Stem cells differ from say skin cells. In stem cells, all 24,000 genes are functioning and they have not yet differentiated, but skin cells are differentiated and they have shut off all other genes except the skin cell genes.

To the above toxic agents, I attach dyes to attack one of the carcinoma cells. The toxic group is activated by cell's enzyme to produce a positive carbon ion called carbonium ion. It is extremely reactive; it binds to all four nucleotides (AT and GC) which form the DNA. But it preferentially binds to N-7 of guanine killing the stem cells. Professor Ross and I have demonstrated the attack on N-7 of guanine using the radiolabeled study.

If I am accidentally exposed to any of the above toxic agents, I do not die of mustard poisoning; I would be frozen to death. What happens is the following: each cell carries hundreds of mitochondrial cells (mitochondria are foreign cells called prokaryotes without nuclear membrane captured by human cells during the evolutionary period, millions of years ago; they live in symbiotic relationship; to perform daily function, mitochondria provide energy to human cells and human cells provide free food and free housing to the mitochondria) which carry energy-rich phosphate bonds. They produce energy by breaking phosphate bonds in which a chemical called ATP (adenosine triphosphate) is broken down to ADP (adenosine diphosphate) which is further broken down to AMP (adenosine monophosphate). As normal cell grows, an enzyme attaches inorganic phosphate to the AMP regenerating ATP. If mitochondrial cells die, there is no energy available.

made AZQ (US Patent 4,146,622) and 45 patentable analogs [17–19]. Years later, I was honored for my work on developing AZQ. Almost 20 years later, for translating my work from mouse to man and making AZQ (US Patent 4,146,622) for treating brain cancer, I was honored with the "2004 NIH Scientific Achievement Award," one of the America's highest awards in medicine (**Figure 2**). I was also honored by the Government of India with Vaidya Ratna (Gold

**Figure 3.** His excellency, Dr. A.P.J. Abdul Kalam, the President of India greeting Dr. A. Hameed Khan, discoverer of anticancer AZQ, after receiving 2004, Vaidya Ratna, the Gold Medal, one of the India's highest awards in medicine at the

The Impact of Sequencing Human Genome on Drug Design to Treat Oral Cancer

http://dx.doi.org/10.5772/intechopen.80231

47

Rashtrapathi Bhavan (Presidential Palace), in Delhi, India, during a reception held on April 2, 2004.

In spite of all the risks, fear, and challenges, the zeal and the enthusiasm that I had to design drugs to attack brain cancer like AZQ is not there to treat oral or lung cancers. Do you know why because I know in my heart, the patient once cured will go back to smoking again. He

**Figure 4.** Gold Medal for Dr. Khan. Dr. A. Hameed Khan, a scientist at the National Institutes of Health (NIH), USA, and an American Scientist of Indian origin, was awarded on April 2, 2004. Vaidya Ratna, the Gold Medal, one of the India's highest awards in medicine for his discovery of AZQ (US Patent 4,146,622) which is now undergoing clinical trials for

Medal) (**Figure 3**).

treating brain cancer.

cannot help it; it is an addiction (**Figure 4**) [20, 21].

As I said above, NIH is the largest biomedical center in the world. It has unlimited facilities (chemicals, equipment, and personnel). Twenty-one thousand best and brightest scientists selected from Ivy League schools work in 26 institutes in more than 3000 labs. I had sent NIH over 120 drugs for NCI screening program [14–16]. During the 3-year period at NIH labs, I

**Figure 2.** 2004 NIH Scientific Achievement Award presented to Dr. Hameed Khan by Dr. Elias Zerhouni, the Director of NIH during the NIH/APAO award ceremony held on December 3, 2004. Dr. Khan is the discoverer of AZQ (US Patent 4,146,622), a novel experimental drug specifically designed to shut off a gene that causes brain cancer for which he receives a 17-year royalty for his invention (License Number L-0I9-0I/0). To this date, more than 300 research papers have been published on AZQ. The award ceremony was broadcast live worldwide by the Voice of America (VOA). Dr. Khan is the first Indian to receive one of the America's highest awards in Medicine.

The Impact of Sequencing Human Genome on Drug Design to Treat Oral Cancer http://dx.doi.org/10.5772/intechopen.80231 47

pass through various layers of our skin from ectoderm to mesoderm to endoderm. They easily enter the cell nucleus destroying the beta and gamma cell which develop immunity. Then they enter the nuclear membrane where they find the stem cells. Stem cells differ from say skin cells. In stem cells, all 24,000 genes are functioning and they have not yet differentiated, but skin cells are differentiated and they have shut off all other genes except the skin cell genes.

To the above toxic agents, I attach dyes to attack one of the carcinoma cells. The toxic group is activated by cell's enzyme to produce a positive carbon ion called carbonium ion. It is extremely reactive; it binds to all four nucleotides (AT and GC) which form the DNA. But it preferentially binds to N-7 of guanine killing the stem cells. Professor Ross and I have

If I am accidentally exposed to any of the above toxic agents, I do not die of mustard poisoning; I would be frozen to death. What happens is the following: each cell carries hundreds of mitochondrial cells (mitochondria are foreign cells called prokaryotes without nuclear membrane captured by human cells during the evolutionary period, millions of years ago; they live in symbiotic relationship; to perform daily function, mitochondria provide energy to human cells and human cells provide free food and free housing to the mitochondria) which carry energy-rich phosphate bonds. They produce energy by breaking phosphate bonds in which a chemical called ATP (adenosine triphosphate) is broken down to ADP (adenosine diphosphate) which is further broken down to AMP (adenosine monophosphate). As normal cell grows, an enzyme attaches inorganic phosphate to the AMP regenerating ATP. If mito-

As I said above, NIH is the largest biomedical center in the world. It has unlimited facilities (chemicals, equipment, and personnel). Twenty-one thousand best and brightest scientists selected from Ivy League schools work in 26 institutes in more than 3000 labs. I had sent NIH over 120 drugs for NCI screening program [14–16]. During the 3-year period at NIH labs, I

**Figure 2.** 2004 NIH Scientific Achievement Award presented to Dr. Hameed Khan by Dr. Elias Zerhouni, the Director of NIH during the NIH/APAO award ceremony held on December 3, 2004. Dr. Khan is the discoverer of AZQ (US Patent 4,146,622), a novel experimental drug specifically designed to shut off a gene that causes brain cancer for which he receives a 17-year royalty for his invention (License Number L-0I9-0I/0). To this date, more than 300 research papers have been published on AZQ. The award ceremony was broadcast live worldwide by the Voice of America (VOA). Dr. Khan

is the first Indian to receive one of the America's highest awards in Medicine.

demonstrated the attack on N-7 of guanine using the radiolabeled study.

chondrial cells die, there is no energy available.

46 Prevention, Detection and Management of Oral Cancer

**Figure 3.** His excellency, Dr. A.P.J. Abdul Kalam, the President of India greeting Dr. A. Hameed Khan, discoverer of anticancer AZQ, after receiving 2004, Vaidya Ratna, the Gold Medal, one of the India's highest awards in medicine at the Rashtrapathi Bhavan (Presidential Palace), in Delhi, India, during a reception held on April 2, 2004.

made AZQ (US Patent 4,146,622) and 45 patentable analogs [17–19]. Years later, I was honored for my work on developing AZQ. Almost 20 years later, for translating my work from mouse to man and making AZQ (US Patent 4,146,622) for treating brain cancer, I was honored with the "2004 NIH Scientific Achievement Award," one of the America's highest awards in medicine (**Figure 2**). I was also honored by the Government of India with Vaidya Ratna (Gold Medal) (**Figure 3**).

In spite of all the risks, fear, and challenges, the zeal and the enthusiasm that I had to design drugs to attack brain cancer like AZQ is not there to treat oral or lung cancers. Do you know why because I know in my heart, the patient once cured will go back to smoking again. He cannot help it; it is an addiction (**Figure 4**) [20, 21].

**Figure 4.** Gold Medal for Dr. Khan. Dr. A. Hameed Khan, a scientist at the National Institutes of Health (NIH), USA, and an American Scientist of Indian origin, was awarded on April 2, 2004. Vaidya Ratna, the Gold Medal, one of the India's highest awards in medicine for his discovery of AZQ (US Patent 4,146,622) which is now undergoing clinical trials for treating brain cancer.
