Biophysical Studies on the Effect of the 13 Position Substitution of the Anticancer Alkaloid Berberine on Its DNA Binding

The structural effects and thermodynamics of the DNA binding of six berberine analogues with alkyl chains of varying length and a terminal phenyl group at the C-13 position were investigated. All the analogues bound DNA noncooperatively in contrast to the cooperative binding of berberine. The binding affinity was higher and the effect of the chain length was only up to (CH2)3, after which the binding affinity decreased slightly. Intercalative binding with strong stabilization of the DNA helix was revealed. Binding resulted in the weakening of the base stacking with moderate conformational changes within the B-form. The binding was entropy driven in each case, the entropy contribution to the free energy increasing with the chain length up to the threshold (CH2)3. The complexation was dominated by nonpolyelectrolytic forces in each case; polyelectrolytic forces contributed only a quarter to the total free energy at 50 mM [Na+]. Overall, the phenylalkyl substitution at the C-13 position considerably enhanced the DNA binding and was highest for the analogue with (CH2)3. Structural and thermodynamic data on the DNA binding aspects of the substituted berberines are presented in comparison with berberine

Ecophysiological and phytochemical responses of Salvia sinaloensis Fern. to drought stress

Abstract Salvia sinaloensis Fern. (sage) is a medicinal plant containing plant secondary metabolites (PSMs) with antioxidant properties. The current study investigated the effects of drought stress on S. sinaloensis morphological and ecophysiological traits, and active constituent production. Sage plants were cultivated in controlled conditions for 34 days and exposed to full irrigation as control, half irrigation, or no irrigation. Changes in growth index (G.I.), dry biomass, leaf water potential (LWP), physiological parameters, active compounds, volatilome (BVOCs) and essential oils (EOs) were determined. Not irrigated plants showed a decrease in total chlorophyll content (~ − 14.7%) and growth (G.I., ~ − 59.4%) from day 18, and dry biomass at day 21 (− 56%), when the complete leaf withering occurred (LWP, − 1.10 MPa). Moderate drought stressed plants showed similar trends for chlorophyll content and growth but kept a constant LWP (− 0.35 MPa) and dry biomass throughout the experiment, as control plants. Carotenoids were not affected by water regimes. The photosynthetic apparatus tolerated mild to severe water deficits, without a complete stomatal closure. Plants under both stress conditions increased the percentage of phenols and flavonoids and showed altered BVOC and EO chemical profiles. Interestingly Camphor, the main EO oxygenated monoterpene, increased in moderate stressed plants while the sesquiterpene hydrocarbon Germacrene D decreased. The same trend was seen in the headspace under stress severity. The data evidenced a possible role of the active molecules in the response of S. sinaloensis plants to drought stress. Taking together, these findings point at S. sinaloensis as a potential drought adaptive species, which could be used in breeding strategies to obtain sages with high quality PSMs,saving irrigation water