Sergio Pinheiro

Synthesis of new glycoporphyrin derivatives through carbohydrate-substituted α-diazoacetates

The reaction of carbohydrate-substituted α-diazoacetates with meso-tetrakis(pentafluorophenyl)porphyrinatozin(II) allows the synthesis of new glyco-hydroporphyrin derivatives.

Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives.

Recently, many efforts have been made to develop N‐methyl‐d‐aspartic acid receptor antagonists for treating different pathological conditions such as thrombo‐embolic stroke, traumatic head injury, Huntington’s, Parkinson’s, and Alzheimer’s diseases). However, as side‐effects limit the use of most antagonists, new drugs are still required. In this work, we performed a (quantitative) structure‐activity relationship analysis of 17 phenyl‐amidine derivatives (1a–1q), reported as N‐methyl‐d‐aspartic acid receptor antagonists, and used this data to rationally design the triazolyl‐amidines. The best (quantitative) structure‐activity relationship model constructed by multiple linear regression analysis presented high data fitting (Ru2003=u20030.914) was able to explain 83.6% of the biological data variance (R2u2003=u20030.836), presented a satisfactory internal predictive ability (Q2u2003=u20030.609) and contained the descriptors (EHOMO, Ovality and cLogP). Our assays confirmed that glutamate promotes an extensive cell death in avian neurons (77%) and 2a and 2b protected the neurons from the glutamate effect (from 77% to 27% and 45%, respectively). The results of neurotoxicity and cytotoxicity on Vero cells suggested the favorable profile of 2a and 2b. Also, the molecular modeling used to predict the activity, the interaction with the receptor and the pharmacokinetic and toxicity of the triazolyl‐amidines pointed them as a promising class for further exploration as N‐methyl‐d‐aspartic acid receptor antagonists.

Subchronic toxicity and anti-HSV-1 activity in experimental animal of dolabelladienetriol from the seaweed, Dictyota pfaffii

&NA; This study examined in rats the subchronic toxicity and anti‐ HSV‐1activity after oral administration of dolabelladienetriol (D1), a diterpene isolated from the seaweed Dictyota pfaffii. In subchronic toxicity (SCT) tests, female rats received D1 by gavage 15 mg/kg/day (n = 5) for 50 days, and general behavior, death, hematological, biochemical and histological changes in the liver, kidney, stomach, and duodenum were determined. For the anti‐HSV‐1 activity, female mice were infected and treated orally with a dose of 20 mg/kg (n = 5) twice a day with D1 and any lesions in the skin were then recorded for 18 days. Dolabelladienetriol in SCT did not significantly change behavior, body weight, hematological or biochemical profiles. The liver and kidneys, however, showed some alterations in rats treated with D1, similar to those in rats treated with ACV, while the other tissues had no significant changes. The anti‐HSV‐1 activity of D1 had a similar efficacy to the ACV drug control in mice. Our results showed that D1 has potential commercial development as a new HSV‐1drug. HighlightsSubchronic oral toxicity of dolabelladienetriol tested in Wistar rats.Low toxicity of dolabelladienetriol in 15 mg/kg concentration for 50 days.Therapeutic effective of dolabelladienetriol (20/mg/day) against HSV‐1 in BALB/c.