‘Phormidin’, a novel, better fatty acid synthase inhibitor from marine
cyanobacteria, Phormidium Ambiguum
Abstract
Background and Purpose: Fatty acid synthase (FAS) is an attractive drug
target for the treatment of cancer, obesity and microbial infections.
Since FAS has an important role in primary metabolic process, targeting
FAS by non-cross-reacting inhibitors will be operationally difficult to
implement, though attractive. Experimental Approach: A novel FAS
inhibitor, Phormidin, from the marine cyanobacteria, Phormidium ambiguum
is reported. Its structure is similar to C75, the FAS inhibitor with a
17 carbon aliphatic chain and an open 6 carbon ring. But, it is
comparatively less similar to Celurinin, another known FAS inhibitor
lacking the epozxy ring. Key Results: In vitro assay of phormidin
cytotoxicity with A549 lung carcinoma cell line showed it to be more
active than cerulenin and C75, with an IC50 value 76.034 µg/mL, compared
to 86.419 µg/mL for Cerulenin and 99.034 µg/mL for C75. Conclusion and
Implications: Enzyme inhibition assay of microbial and mammalian FASs
showed promising results, with potential to develop better FAS inhibitor
drugs.