Docking studies of flavonoid compounds as inhibitors of β-ketoacyl acyl carrier protein synthase I (Kas I) of Escherichia coli

• β-ketoacyl-acyl carrier protein synthase I (FabB) may be one of the most attractive biochemical pathways to be used as the target for new anti-bacterial agents.
• Flavonoids are naturally occurring polyphenolic compounds that they have been reported to possess many useful properties, including anti-inflammatory activity, estrogenic activity, enzyme inhibition, anti-microbial activity.
• We suggest two flavonoid compounds, genistein and isorhamnetin, can be used as a hit molecule against the fatty acid synthase in bacteria.
• Genistein and isorhamnetin, have similar binding poses and interactions with β-ketoacyl acyl carrier protein synthase I compared to the standard (thiolactomycin).
• This in silico study is actually an added advantage to screen the β-ketoacyl acyl carrier protein synthase I inhibition.

Escherichia coli is one of the most frequent causes of many common bacterial infections, including cholecystitis, bacteremia, cholangitis, urinary tract infection (UTI), traveler’s diarrhea and other clinical infections such as neonatal meningitis and pneumonia. The fatty acid biosynthesis is essential for the bacterial viability and growth. There are three types of β-ketoacyl acyl carrier protein synthase (KAS) which are important for overcoming the bacterial resistance problem. β-ketoacyl acyl carrier protein synthase I (KAS I) is member of the condensing enzyme family, which is a key catalyst in bacterial fatty acid biosynthesis, and thus an attractive target for novel antibioticsis related to the elongation of unsaturated fatty acids in bacterial fatty acid synthesis and can be a good therapeutic target of designing novel antibiotics. In this report, we performed docking study of E. coli (KAS I) and 50 flavonoids. Out of these 50 flavonoids, there are two compounds, genistein and isorhamnetin, that showed the superior binding energy while fully satisfying the conditions of drug likeliness. The predicted binding energy of genistein and isorhamnetin toward KAS I are −135.76 kcal/mol and −132.42 kcal/mol, respectively. These energies favorably compare to the biding energy of known drugs thiolactomicin and cerulenin that are −90.26 kcal/mol and −99.64 kcal/mol, respectively. The method used was docking with the selected E. coli (KAS I-PDB ID-1FJ4) using iGemdock. This was also found to obey the Lipinski’s guidelines of five and to show the drug likeliness and bioavailability.

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