|Systematic (IUPAC) name|
|Bioavailability||25% to 89%|
|Half-life||1.5 ± 0.8 hours|
|Excretion||Renal, significantly metabolised|
|Molecular mass||305.2 g/mol|
|(what is this?)|
An alkylating agent adds an alkyl group (CnH2n+1) to DNA. It attaches the alkyl group to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring.
Mechanism of action
Melphalan chemically alters through alkylation of the DNA nucleotide guanine, and causes linkages between strands of DNA. This chemical alteration inhibits DNA synthesis and RNA synthesis, functions necessary for cells to survive. These changes cause cytotoxicity in both dividing and non-dividing tumor cells.
Oral or intravenous; dosing varies by purpose and route of administration as well as patient weight.
Common side effects include:
- Nausea and vomiting, and oral ulceration.
- Bone marrow suppression, including
Less common side effects include:
- Severe allergic reactions
- Pulmonary fibrosis (scarring of lung tissue) including fatal outcomes (usually only with prolonged use)
- Hair loss
- Interstitial pneumonitis
- Irreversible bone marrow failure due to melphalan not being withdrawn early enough.
- Cardiac arrest.
Another amino acid-like drug is the antineoplastic agent melphalan. Tumor cells spend less time in resting phases than normal cells so at any given time, they are more likely to be metabolically active than most normal host cells. The rationale behind incorporating an alkylating function in a molecule resembling a primary cellular metabolite was to get a greater safety margin by fooling tumor cells into taking up the toxin preferentially.
p-Nitrophenyl-alanine was converted to its phthalimide by heating with phthalic anhydride, and this was converted to its ethyl ester. Catalytic hydrogenation produced the corresponding aniline. Heating in acid with oxirane, followed by treatment with phosphorus oxychloride provided the bischloride, and removal of the protecting groups by heating in hydrochloric acid gave melphalan.
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