Abstract:
Artocarpus hirsutus Lam., or wild jack, a perennial tree of the Western Ghats of peninsular India, serves as a rich
source of flavonoids. The indigenous knowledge of this multipurpose flora chronicles the efficient property of its bark as a natural
treatment for various skin infections. Herein, we describe a rational explanation of this traditional knowledge via a broader evaluation
of inhibitory activity of one of its phytoconstituents, cudraflavone C (Cud C), a prenyl flavone isolated from stem bark against
diverse multidrug-resistant Staphylococcus aureus along with decidedly potent synergy combinations with a standard drug,
gentamycin, especially against gentamycin-resistant S. aureus NRS 10119. Cud C exhibited equipotent MIC (4 μg/mL) against a
varied array of MDR strains comprising MRSA, VRSA, and VRE and was nontoxic toward eukaryotic cells with a sizable selectivity
index (SI 25−50). Cud C displayed concentration-dependent bactericidal activity against planktonic cells, an excellent biofilm
disruption property exceeding that of levofloxacin and vancomycin against preformed S. aureus biofilm, and an enhanced capability
to kill intracellular S. aureus more potently than vancomycin, thus exemplifying its position as an antibacterial lead candidate. In
addition, S. aureus was unable to generate resistance to Cud C even after exposure for more than 40 days, whereas it generated
resistance to levofloxacin within ∼20 days of exposure. Therefore, the naturally occurring prenylflavone Cud C can be accounted for
as one of the reasons for the reported antibacterial properties of the bark of A. hirsutus. Taken together, detailed biological studies
propose that Cud C can be considered as an effective antibacterial drug candidate against MDR S. aureus, which is fast becoming a
significant threat to public health worldwide.
