Identification of (−)(E)-N-[2(S)-Hydroxy-2-(4-hydroxyphenyl) ethyl]ferulamide, a Natural Product Isolated from Croton Pullei: Theoretical and Experimental Analysis

Abstract: Ferulic acid (FA) and its derivatives (FADs) are known for a variety of biological activities, such as photo-protective agent, antioxidant, antiatherogenic and antiplasmodial activities. During structural definition of a FAD isolated from Croton pullei, the possibility of a heterologous series made this definition difficult. In this regard, computational simulations were performed using theoretical calculations at DFT level to predict Infrared (IR) and Nuclear Magnetic Resonance (NMR) data. The IR and NMR 13 C and 1 H data were compared with the theoretical calculations performed for three structural possibilities of a heterologous series. The theoretical results were compared with the experimental data through linear regression in order to define the most probable structure and showed satisfactory values

DADOS ESPECTROSCÓPICOS DE DITERPENOS LABDÂNICOS: UMA ANÁLISE TEÓRICA VIA RMN E DFT

Labdane diterpenes exhibit important bioactivities such as cardiovascular effects in rats as well as effects in the treatment of autoimmune diseases and Alzheimer syndrome. Recently, the labdane diterpenes ent-13-epi-manoil oxide, ribenone and ribenol were isolated from Croton palanostigma. The computational method DFT/B3LYP/cc-pVDZ was used to optimize the structures of these diterpenes and to calculate infrared data. Chemical shifts (δH and δC) of the minimum energy structures (local minimum) were calculated and compared with the experimental data. Comparison of the NMR data by simple linear regression (SLR) showed satisfactory statistical results with a correlation coefficient (R2) and predictive ability (Q2) of over 98%. The predicted NMR data were used to confirm the δH values that have not been published

Synthesis, X-ray crystal structure and theoretical calculations of antileishmanial neolignan analogues

The synthesis and X-ray crystal diffraction structure of two analogues of neolignans, 2-(4-chlorophenyl)-1-phenylethanone (20) and 2-[(4-chlorophenyl)thio]-1-(3,4-dimethoxyphenyl)propan-1-one (12) is described. The compound 12 presents activity against intracellular Leishmania donovani and Leishmania amazonensis amastigotes that cause cutaneous and visceral leishmaniasis. In addition, the density functional theory (DFT) with the B3LYP hybrid functional was employed to calculate a set of molecular descriptors for nineteen synthetic analogues of neolignans with antileishmanial activities. Afterwards, the stepwise discriminant analysis was performed to investigate possible relationship between the molecular descriptors and biological activities. Through this analysis the compounds were classified into two groups active and inactive according to their degree of biological activities, and the more important properties were charges on some key atoms, electronic affinity and ClogP

Essential oil composition of Croton palanostigma Klotzsch from north Brazil

The essential oils of leaves, twigs, branches, trunk bark and fruits of Croton palanostigma were analyzed by GC and GC-MS. The main compounds found in the oil of the leaves were linalool (25.4%), (E)-caryophyllene (21.0%), methyleugenol (17.2%) and β-elemene (6.0%); in the oil of the twigs were α-pinene (41.4%), limonene (29.0%), sabinene (11.5%) and β-pinene (5.7%); in the oil of the branches were methyleugenol (24.1%), (E)-methylisoeugenol (15.3%), α-pinene (11.2%) and (E)-caryophyllene (8.5%); in the oil of the trunk bark were a-pinene (31.6%), methyleugenol (25.6%) and (E)-methylisoeugenol (23.7%); and in the oil of the fruits were linalool (42.7%), methyleugenol (16.3%) and β-elemene (6.4%). Statistical analysis showed that the leaves and fruit, and the branches and trunk bark, have significant similarities between them. In addition, the trunk bark oil has high brine shrimp larvicidal activity (LC50, 3.71 ± 0.01 mg mL-1)

Leishmanicidal Activity of (+)-Phyllanthidine and the Phytochemical Profile of Margaritaria nobilis (Phyllanthaceae)

The effects of the Securinega alkaloid (+)-phyllanthidine on Leishmania (L.) amazonensis and the first chemical investigation of Margaritaria nobilis L.f. (Phyllanthaceae) are described. Treating the parasites with this alkaloid caused a dose-dependent reduction in promastigote growth of 67.68% (IC50 82.37 μg/mL or 353 µM) and in amastigote growth of 83.96% (IC50 49.11 μg/mL or 210 µM), together with ultrastructural alterations in the promastigotes. No cytotoxic effect was detected in mammalian cells (CC50 1727.48 µg/mL or CC50 5268 µM). Classical chromatographic techniques and spectral methods led to the isolation and identification of betulinic acid, kaempferol, corilagin, gallic acid and its methyl ester, besides (+)-phyllanthidine from M. nobilis leaves and stems. Margaritaria nobilis is another source of the small group of Securinega alkaloids, together with other Phyllanthaceae (Euphorbiaceae s.l.) species. The low toxicity to macrophages and the effects against promastigotes and amastigotes are suggestive that (+)-phyllanthidine could be a promising antileishmanial agent for treating cutaneous leishmaniasis

A Computational Approach Applied to the Study of Potential Allosteric Inhibitors Protease NS2B/NS3 from Dengue Virus

Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents