Saponins are potential
wide-spectrum antitumor drugs, and copper(I)
catalyzed azide–alkyne 1,3-dipolar cycloaddition is a suitable
approach to synthesizing saponin-like compounds by regioselective
glycosylation of the C2/C3 hydroxyl and C28 carboxylic groups of triterpene
aglycones maslinic acid (MA) and oleanolic acid (OA). Biological studies
on the T-84 human colon carcinoma cell line support the role of the
hydroxyl groups at C2/C3, the influence of the aglycone, and the bulky
nature of the substituents in C28. OA bearing a α-d-mannose moiety at C28 (compound 18) focused our interest
because the estimated inhibitory concentration 50 was similar to that
reported for ginsenoside Rh2 against colon cancer cells and it inhibits
the G1–S phase transition affecting the cell viability
and apoptosis. Considering that triterpenoids from natural sources
have been identified as inhibitors of nuclear factor kappa-light-chain-enhancer
of activated B cell (NF-κB) signaling, docking studies were
conducted to evaluate whether NF-κB may be a potential target.
Results are consistent with the biological study and predict a similar
binding mode of MA and compound 18 to the p52 subunit
from NF-κB but not for OA. The fact that the binding site is
shared by the NF-κB inhibitor 6,6-dimethyl-2-(phenylimino)-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-one supports the
result and points to NF-κB as a potential target of both MA
and compound 18.
Persistent organic pollutants are a group of chemical compounds of global concern due to the health damages caused by the exposure to them. Their capacity as endocrine disrupters is one of their main characteristics, being women in reproductive age the most vulnerable population. The aim of the present study was to evaluate the effect of exposure to a mixture of pesticides in the menstrual cycle of a sample of 29 teenagers between the ages of 12 and 17 years old from El Refugio, San Luis Potosi, Mexico, a community whose predominant activity is agriculture. The participants were trained to record in a diary/ logbook all the events related to their menstrual cycle. Serum levels of sex hormones were measured by chemiluminescence, and plasma concentrations of organochlorine (OC) pesticides and the level of dialkyl phosphates metabolites (DAPs) of organophosphorus agrochemicals presented in urine were measured through gas chromatographymass spectrometry. Around 41.6 % of the participants presented some alteration in their hormonal levels, mainly of follicle-stimulating hormone and progesterone. Of these, OC pesticides in plasma were detected in 62 % (ΣOC = 1651.25 ng/g of lipid), and 66 % had detectable levels of DAPs (ΣDAP = 153.82 mg/g of creatinine). Together, these results suggest damage to the endocrine system that could be generated by exposure to a mixture of OC and organophosphorus pesticides could generate.
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