Gastroprotective role of a flavonoid-rich subfraction from Fridericia chica (Bonpl.) L. G. Lohmann: a medicinal plant used in the Amazon region.

Fridericia chica is an Amazonian plant used to treat stomach disorders. However, the pharmacological activity of flavonoids in the extract has yet to be investigated. Therefore, we considered that a flavonoid-rich F. chica subfraction (FRS) has gastroprotective functions. For this, before the induction of gastric ulcers with ethanol or piroxicam, the rats received vehicle (water), omeprazole (30 mg/kg), or FRS (30 mg/kg), and the ulcer area was measured macro and microscopically, and the antisecretory action was investigated in pylorus-ligated rats. In addition, the roles of nitric oxide (NO) and nonprotein sulfhydryl compounds (NP-SH) in the gastroprotective effects of FRS were studied. FRS reduced ethanol- and piroxicam-induced ulcerations by 81% and 77%, respectively, as confirmed histologically. Antioxidant effects were observed for FRS through the maintenance of GSH and LPO levels, and the SOD and CAT activity similar to those found in the nonulcerated group. Moreover, FRS avoided the increase in MPO activity and TNF, IL-6, IL-4 and IL-10 levels. Moreover, mucin staining increased in ulcerated rats receiving FRS, and the pharmacological mechanism gastroprotective seems to involve the NO and NP-SH in addition to antisecretory actions. The chemical study by mass spectrometry confirmed the presence of flavonoids in FRS, and molecular docking studies have shown that these compounds interact with cyclooxygenase-1 and NO synthase. Furthermore, there was no indication that FRS had cytotoxic effects. Our results support the popular use of F. chica, and we conclude that the gastroprotection effect promoted by FRS can be attributed to the combined effect of the flavonoids.

Rate coefficients for the O + H2 and O + D2 reactions: how well ring polymer molecular dynamics accounts for tunelling.

We present here extensive calculations of the O(3P) + H2 and O(3P) + D2 reaction dynamics spanning the temperature range from 200 K to 2500 K. The calculations have been carried out using fully converged time-independent quantum mechanics (TI QM), quasiclassical trajectories (QCT) and ring polymer molecular dynamics (RPMD) on the two lowest lying adiabatic potential energy surfaces (PESs), 13A' and 13A'', calculated by Zanchet et al. [J. Chem. Phys., 2019, 151, 094307]. TI QM rate coefficients were determined using the cumulative reaction probability formalism on each PES including all of the total angular momenta and the Coriolis coupling and can be considered to be essentially exact within the Born-Oppenheimer approximation. The agreement between the rate coefficients calculated by using QM and RPMD is excellent for the reaction with D2 in almost the whole temperature range. For the reaction with H2, although the agreement is very good above 500 K, the deviations are significant at lower temperatures. In contrast, the QCT calculations largely underestimate the rate coefficients for the two isotopic variants due to their inability to account for tunelling. The differences found in the disagreements between RPMD and QM rate coefficients for the reactions for both the isotopologues are indicative of the ability of the RPMD method to accurately describe systems where tunelling plays a relevant role. Considering that both reactions are dominated by tunelling below 500 K, the present results show that RPMD is a very powerful tool for determining rate coefficients. The present QM rate coefficients calculated on adiabatic PESs slightly underestimate the best global fits of the experimental measurements, which we attribute to the intersystem crossing with the singlet 11A' PES.

Improving Properties of Podophyllic Aldehyde-Derived Cyclolignans: Design, Synthesis and Evaluation of Novel Lignohydroquinones, Dual-Selective Hybrids against Colorectal Cancer Cells.

New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates were connected through different aliphatic or aromatic linkers. Among the evaluated hybrids, the L-HQ with the aromatic spacer clearly displayed the in vitro dual cytotoxic effect derived from each starting component, retaining the selectivity and showing a high cytotoxicity at short (24 h) and long (72 h) incubation times (4.12 and 0.0450 µM, respectively) against colorectal cancer cells. In addition, the cell cycle blockade observed by flow cytometry studies, molecular dynamics, and tubulin interaction studies demonstrated the interest of this kind of hybrids, which docked adequately into the colchicine binding site of tubulin despite their large size. These results prove the validity of the hybridization strategy and encourage further research on non-lactonic cyclolignans.