Ademir F. Morel

Antinociceptive Effects of 14-Membered Cyclopeptide Alkaloids

The analgesic potential of six 14-membered-ring cyclopeptide alkaloids, namely, franganine (1), discarine B (2), scutianines B (3), C (4), and D (5), and adouetine X (6), have been investigated. Among the compounds tested, only franganine (1) and adouetine X (6) produced antinociceptive effects in a mouse model of acute pain, without inducing undesirable side effects. Furthermore, compound 6 also exhibited a pronounced analgesic effect in a chronic neuropathic pain model in mice. It has been found that adouetine X (6) can decrease the activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase in vitro. Thus, the present findings have demonstrated that adouetine X (6) is a promising analgesic agent.

Peptide alkaloids of Scutia buxifolia

Abstract From the bark extract of S. buxifolia , the known alkaloids scutianines B, C, D and E, and the new one, scutianine H, have been isolated. The structure of scutianine H, based mainly on its MS fragmentation and on the MIKES (mass-analysed ion kinetic energy spectrum) of the base ion peak, is suggested. From the 13 C NMR spectral analysis of the diastereoisomeric scutianines D and E, information for the assignment of the stereochemistry of the β-hydroxyleucine unit in related alkaloids was also obtained.

Cyclopeptide alkaloids: stereochemistry and synthesis of the precursors of discarines C and D and myrianthine A.

The stereochemistry of discarines C (1) and D (2) and myrianthine A (3), three cyclopeptide alkaloids isolated from Discaria febrifuga, was determined by a combination of NMR studies of 1-3, enantioselective gas chromatography, and comparison of NMR data with those of synthetic tripeptides. For the synthesis of peptides, the nonproteinogenic amino acid 3-phenylserine was also obtained in its four diastereoisomeric forms (l and d threo, obtained by recrystallization of the diastereoisomeric tripeptide, and l and d erythro, obtained by a Mitsunobu reaction with the threo-tripeptides). The general synthetic strategy described in this paper allows the tripeptide to be obtained with the free N-terminal extremity protected or dimethylated. This strategy also allows the synthesis of the corresponding peptide with an imidazolidinone ring.

Absolute configuration of franganine.

The absolute configuration of franganine (1), a cyclopeptide alkaloid isolated from the methanol root bark extract of Discaria americana, was established on the basis of detailed NMR spectroscopic data and X-ray diffraction analysis of its salt (2).

Chemical Composition and Inhibitory Effects of Hypericum brasiliense and H. connatum on Prolyl Oligopeptidase and Acetylcholinesterase Activities

BACKGROUNDnThe genus Hypericum (family Clusiaceae) comprises various species that are used in traditional medicine, such as wound healing, antidepressant, and anticancer agents.nnnOBJECTIVEnThe aim of this study was to evaluate the inhibitory capacity of extracts and fractions from two Hypericum species used in the Brazilian folk medicine (H. brasiliense and H. connatum) against the enzymes prolyl oligopeptidase (POP), dipeptidyl peptidase-IV (DPP-IV), and acetylcholinesterase (AChE), as well as to identify their main active constituents.nnnMETHODSnDried aerial parts of H. connatum and H. brasiliense were subjected to extraction with 8:2 methanol-H2O. Each hydroalcoholic extract was fractioned resulting in ethyl acetate and aqueous fractions. The activity of POP, DPP-IV and AChE was determined in vitro in 96-well microplates.nnnRESULTSnThe main components identified in the plant extracts were chlorogenic acid (1), quercitrin (2), rutin (3), quercetin (4), and isoquercitrin (5). Hydroalcoholic extracts, ethyl acetate and aqueous fractions showed high POP inhibitory activity with IC50 values of 2.6 to 3.7 µg/mL. AChE and DPP-IV inhibitory effects were very low for all extracts and substances.nnnCONCLUSIONnChlorogenic acid (1) and quercetin (4) were the main constituent responsible for the activity observed against POP. Parallel artificial membrane permeability assay of ethyl acetate fractions of both species showed that the metabolite that can effectively pass through the lipid membrane is 4, the aglycone form of 2, 3 and 5.

Chemical constituents from Valeriana polystachya Smith and evaluation of their effects on the acetylcholinesterase and prolyl oligopeptidase activities

Two new iridoids (1-2) and a new decomposition product of valepotriates (3), together with fifteen known compounds (4-18) were isolated from the roots and rhizomes of Valeriana polystachya Smith, a native species from the Pampa Biome. Their structures were elucidated by means of NMR spectroscopy, mass spectrometry and optical rotation. The structures of 3 and 18 were further confirmed by single crystal X-ray diffraction analysis. In the group of the isolated compounds, 6β-hydroxysitostenone, hydroxymaltol and isovillosol were isolated from the Valeriana genus for the first time. The extracts and isolated compounds were evaluated for their in vitro activities against acetylcholinesterase (AChE) and prolyloligopeptidase (POP). Compounds 7, 9 and 11 showed weak inhibitory activity against AChE, while 3 and 5 displayed exceptional POP inhibitory activity, with IC50 values of 5.3u202f±u202f0.07 and 7.9u202f±u202f0.4u202fμM, respectively.

Phytochemical and antimicrobial study of Pilocarpus pennatifolius Lemaire

The investigation of the crude extract of leaves and bark of Pilocarpus pennatifolius Lemaire allowed isolated of a not yet described coumarin, together with three known coumarins (bergapten, xanthotoxin and dimethyl allyl xanthyletin), and a not yet described imidazole alkaloid. All structures were established by means of spectral analysis, including extensive 2D NMR studies. In addition, the alkaloid had its absolute stereochemistry determined by X-ray diffraction. Meanwhile, extracts and pure compounds were tested against various strains of bacteria and fungi, showing promising antimicrobial activities. We highlight the activities of crude bark methanol extract (CBME), of the leaf basic acetate fraction (LBAcF), and of compound 2 against the Gram negative bacteria Shigella flexneri (MICsu202f=u202f7.8, 7.8 and 3.12u202fμg·mL-1, respectively), of compound 5 against the Gram positive Enterococcus fecalis (MICu202f=u202f1.56u202fμg·mL-1), and against two Gram negative bacteria Salmonella enteritidis (MICu202f=u202f1.56u202fμg·mL-1), and Pseudomonas aeruginosa (MICu202f=u202f6.25u202fμg·ml-1). On the other hand, CBME and compounds 3-5 showed excellent activity against the fungus Candida krusei with MICs of 15.6, 1.56, and 3.12u202fμg·mL-1 respectively, as actives or better than the antifungal standard fluconazole (MICu202f=u202f3.12u202fμg·mL-1).

Absolute Configuration of Clemateol

The present study reports the determination of absolute stereochemistry of clemateol, an irregular monoterpene containing an epoxy group, which was isolated as the main component from the essential oil of Calea clematidea (Asteraceae). Its absolute stereochemistry was unambiguously established on the basis of detailed nuclear magnetic resonance (NMR) spectroscopic evidence (JH-H analysis, derivatization as Mosher’s esters and nuclear Overhauser effect (NOESY) spectrum) and also by resonance scattering effects in the single crystal X-ray diffraction (XRD) resolution of its (R)-mandelic acid ester derivative.

Chemical Composition, Antitumoral and Antibacterial Activities of Essential Oils from Leaves and Stem Bark of Nectandra lanceolata (Lauraceae)

Abstract The essential oil of leaves and barks of Nectandra lanceolata, obtained by hydrodistillation, was characterized in terms of its chemical composition by GC-FID, GC-MS and NMR. The analyses and identiûcation pointed by mass fragmentation pattern and retention index revealed the presence of 30 compounds in the oil from leaves and 36 compounds in oil from barks, representing 91.8 % of the total leaf oil and 96.5 % of the bark oil. The major compounds of the leaf oil were E-caryophyllene (12.45 %), biciclogermacrene (18.2 %) and spathulenol (16.7 %). In the oil from barks, the major compounds were guaiol (13.2 %), cubenol (7.6 %), α- epi-cadinol (4.8 %), γ-cadinene (7.6 %), α-pinene (6.9 %). Moreover, were evaluated the potential of inhibition against the resistant bacteria Acinetobacter baumannii and antitumor properties of oils. It was possible to conclude that oil from bark of Nectandra lanceolata present more potent activity than oil from leaves. The essential oil from bark of Nectandra lanceolata showed more activity against K562 (14.6 μg.mL-1) and U251 (37.3 μg.mL-1). The content of these fractions was predominantly of the sesquiterpenes, such as guaiol, cubenol, 1-epi-α-cadinol and caryophyllene oxide, which were enriched after fractio-nation. These fractions were tested in vitro against two human cancer cell lines (786-0 and HT-29) by Sulforhodamine B assay, showing improved activity when compared to the crude oil. The bark oil showed activity against resistant bacteria Acinetobacter bamanni with an inhibition zone of 18 mm and MIC value of 18 mg.mL-1.