Title:Ornithine Decarboxylase Inhibition: A Strategy to Combat Various Diseases
VOLUME: 18 ISSUE: 12
Author(s):Rakesh R. Somani*, Priyanshu R. Rai and Pooja S. Kandpile
Affiliation:Department of Pharmaceutical Chemistry, Vivekanand Education Society`s College of Pharmacy, Chembur (E), Mumbai 400074, Department of Pharmaceutical Chemistry, Vivekanand Education Society`s College of Pharmacy, Chembur (E), Mumbai 400074, Department of Pharmaceutical Chemistry, Vivekanand Education Society`s College of Pharmacy, Chembur (E), Mumbai 400074
Keywords:African sleeping sickness, antibiotic, cancer, malaria, ornithine decarboxylase, polyamines.
Abstract:Ornithine decarboxylase is the first enzyme in the polyamine biosynthetic pathway. It is the
rate-limiting enzyme which is included during the change of ornithine to putrescine which is the first
polyamine. Polyamines (putrescine, spermidine, spermine) are natural and synthetic compounds which
contain two or more amino group. Polyamines are highly implicated in cellular functions such as cell
growth & multiplication, DNA stabilization, gene transcription and translation, ion-channel activity,
etc. Elevated levels of polyamines are found in highly proliferating tumor cells. Hence inhibition of
this enzyme was found useful in cancer. α-DL-difluoromethylornithine(DFMO) (Eflornithine) an enzyme-
activated irreversible inhibitor was the first of this type. However, its use as an anticancer agent
did not continue for long due to various reasons. Polyamines have also been found to play an important
role in other infectious microorganisms. Eflornithine is successfully used in diseases such as African
sleeping sickness and is being researched against a number of tropical diseases. It is widely used
against hirsutism in women. Various other product (putrescine) based analogs and transition state or
PLP (cofactor) based analogs are being synthesized against diseases such as Leishmaniasis, Malaria
and others discussed in the article.
