Parasite Plasmodium falciparum is continuously giving a challenge to human beings by
changing itself against most of the antimalarial drugs and its consequences can be seen in the form of
a huge number of deaths each year especially in the poor and developing country. Due to its drug resistance
ability, new drugs are regularly needed to kill the organism. Many new drugs have been developed
based on different mechanisms. One of the potential mechanisms is to hamper protein synthesis
by blocking the gene expression.
S-Adenosyl-L-homocysteine (SAH) hydrolase is a NAD+ dependent tetrameric enzyme, which is responsible
for the reversible hydrolysis of AdoHcy to adenosine and L-homocysteine, has been recognized
as a new target for antimalarial agents since the parasite has a specific SAH hydrolase. The inhibition
of SAH hydrolase causes the intracellular accumulation of S-Adenosyl-L-homocysteine, elevating
the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase
that catalyzes methylation of the capped structure at the 5′-terminus of mRNA, and other methylation
reaction which is essential for parasite proliferation. In other words, S-Adenosyl-Lhomocysteine
hydrolase regulates methyltransferase reactions. In this way, SAH hydrolase inhibitors
can be used for the treatment of different diseases like malaria, cancer, viral infection, etc. by ultimately
stopping the synthesis of protein. Many antiviral drugs have been synthesized and marketed
which are based on the inhibition of SAH hydrolase.
This review summarises the development of SAH inhibitors developed over the last 20 years and their
potentiality for the treatment of malaria.