Mexican sunflower (Tithonia diversifolia, Asteraceae) volatile oil as a selective inhibitor of Staphylococcus aureus nicotinate mononucleotide adenylyltransferase (NadD)

Tithonia diversifolia, well-known as Mexican sunflower, is an invasive shrub growing in tropical areas of South America, Asia and Africa where it is used as a traditional medicine, ornamental plant and green biomass to improve soil fertility. Given the traditional uses in the treatment of skin infections, we have first analysed the chemical composition and the antimicrobial effects of the essential oil hydrodistilled from inflorescences of T. diversifolia. For the purpose the inhibition zones against a panel of pathogens were measured by the agar diffusion method. In addition, we evaluated the inhibitory effects on several NaMN/NMN adenylyltransferases, which are essential enzymes for NAD biosynthesis in most bacterial pathogens, and also tested the inhibition on the mammalian orthologue enzymes as a promising way to identify novel natural antibiotics. To complete the screening of biological effects, the antioxidant capacity and antiproliferative effects on human tumor cells were evaluated using the DPPH, ABTS, FRAP, and MIT methods. Results showed that T. diversifolia essential oil was mostly active against Staphylococcus aureus with a halo of 14 mm. The essential oil selectively inhibited in vitro the pure NAD biosynthetic enzyme NadD from S. aureus (IC50 of similar to 60 mu g/mL), with basically none or only minor effects on mammalian orthologue enzymes. Finally, the essential oil displayed significant cytotoxic effects on A375, MDA-MB 231, HCT 116 and T98 G tumor cells with IC50 values of 3.02, 3.79, 3.46 and 12.82 mu g/mL, respectively, and noticeable radical scavenging activity on DPPH and ABTS radicals, with IC50 values of 108.8 and 41.7 mu g/mL, respectively.