1)
i) Nitroaromatic compounds
Nitracaine
Nitrophenyl mustard
SN-23862
Heteroaromatic mustards
ii) quinone compounds
Doxorubicin
Daunorubicin
Aclarubicin
Epirubicin
Idarubicin
Natural quinolones Mitomycin C and Porfiromicin. Anti-Cancer Pro-drugs Essay

iii) mechanisms of reduction
Nitroaromatic reduction. The main alkylating effects are due to hydroxylamine Reductive bioactivation of cytotoxic nitroaromatic compounds involves DNA (Avendano and Menendez, 2008)
Quinone reduction. Quinones undergo either one- or two-electron reduction.
iiii) DNA alkylation. Alkylating agents react with the 7 position of guanine, adenine, cytosine and even some sugar phosphate groups in each of the double strands of DNA causing cross-linking that interferes with separation of the strands.
Nitroaromatic compounds. Hydroxylamines give rise to covalent DNA-adduct.

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DNA alkylation by activated nitroaromatic compounds (Avendano and Menendez, 2008).
Quinones. After reduction, a good leaving group at C2 carbon makes quinones good alkylating agents.Anti-Cancer Pro-drugs Essay

2)
iiiii) Antibody-directed enzyme prodrug therapy, also known as ADEPT, is a strategy used to overcome the problem of low chemotherapeutic selectivity. In this technology, an antibody designed against a tumor antigen is linked to a given enzyme and injected to the blood. The tumor thus is enriched with a certain type of enzyme. Next, a prodrug specific to the enzyme is administered. The enriched with the enzyme tumor would activate the prodrug. Thus, the toxic effects of the chemical compound will show its suppressive activity primarily on the malignant cells (Avendano and Menendez, 2008).

ADEPT was introduced in the early 1990’s (Thurston, 2007). This multi-compound scheme first targets the tumor with antibodies and only after that the prodrug is given. The first studies used carboxypeptidase G from Pseudomonas species.

CMDA, a mustard prodrug has already reached clinical trials. This compound in combination with bacterial carboxypeptidase G is mixed with cyclosporine C. CMDA in combination with carboxypeptidase G and cyclosporine counteracts the immune response to the conjugate. The latter complex is injected into the blood. Carboxypeptidase activates CMDA by its ionization. Ionized form of CMDA shows higher activity.Anti-Cancer Pro-drugs Essay

ADEPT approach to chemotherapy with nitrogen mustard. Activated CMDA undergoes ionization to . The electron density in is increased (Avendano and Menendez, 2008)

iiiiii) ADEPT is a promising anticancer strategy. Using this approach, it is theoretically possible to administrate the well-known chemical compounds when their toxic systemic side-effects can be avoided. ADEPT promises that the prodrug would be activated in the tumor cells only, so the malignant cells succumb, while surrounding tissues and other organs avoid the negative impact of systemic chemotherapy. Anti-Cancer Pro-drugs Essay