Isoquinoline alkaloids, especially from the Annonaceae family, have shown biological potential against parasites. Thus, this study aimed to evaluate the potential of the alkaloid fractions of the plant Fusaea longifolia against Plasmodium falciparum and annotate the compounds present in these samples. The tentative characterization of the alkaloids from the leaves and branches of F. longifolia was performed using liquid chromatography coupled to mass spectrometry (LC-MS/MS) and molecular networks. Through manual interpretation of the MS/MS spectra, 18 alkaloids were dereplicated from F. longifolia, 17 of which were reported for the first time in this species. An unpublished putative glycosylated alkaloid was annotated by interpreting the fragmentation data profile. Regarding biological activity, the fractions studied showed high activity against P. falciparum with half-maximal inhibitory concentration (IC50) of 2.42 and 1.60 μg mL-1 for branches and from the leaves, respectively, both similar to the reference standard quinine (IC50 of 1.24 μg mL-1). The structures of the 17 alkaloids were subjected to in silico analysis using molecular docking against four enzymes related to anti-Plasmodium activity (wild type (dm-PfDHFR) and mutant type (qm-PfDHFR), dihydroorotate dehydrogenase (PfDHODH) and purine nucleoside phosphorylase (PfPNP)). Molecular docking revealed strong interactions, especially between oxoxylopine 17 and hydroxycassythicine N-oxide 10, which may be potential new sources against P. falciparum. family parasites Thus samples F LCMS/MS LCMSMS LC MS (LC-MS/MS networks MSMS spectra 1 species profile P halfmaximal half maximal IC50 IC 242 2 42 2.4 160 60 1.6 mL1 mL mL- respectively (IC5 124 24 1.2 mL1. . mL-1) antiPlasmodium anti wild dmPfDHFR dm PfDHFR (dm-PfDHFR qmPfDHFR, qmPfDHFR qm , (qm-PfDHFR) PfDHODH (PfDHODH PfPNP. PfPNP (PfPNP)) interactions Noxide N oxide 10 LCMS IC5 4 2. 16 6 1. (IC 12 (qm-PfDHFR (PfPNP) (PfPNP

The phytochemical investigation of the hexane and methanol extracts from the bark of Duguetia pycnastera Sandwith (Annonaceae) afforded seven known compounds, two asarone-derived phenylpropanoids and five isoquinoline-derived alkaloids. The asarones, γ-asarone (1-allyl-2,4,5-trimethoxybenzene) and 2,4,5-trimethoxy-styrene were isolated of the hexane extract while the aporphine alkaloids, O-methylmoschatoline, lysicamine, nornuciferidine, and guatterine N-oxide, and the benzyltetrahydroisoquinoline alkaloid, (S)-reticuline were isolated of the alkaloid fraction of the methanol extract. This is the first report of these compounds in D. pycnastera. γ-Asarone is being reported for the first time in the Annonaceae. Nornuciferidine is described for the second time in the Annonaceae while guatterine N-oxide is the third register. The structures of the isolated compounds were established by extensive analyses using 1D and 2D NMR spectroscopy in combination with MS. The cytotoxic activity of the isolated compounds (except for nornuciferidine) was evaluated against cancer and non-cancerous cell lines, in which lysicamine was the most active compound, mainly against HL-60, HepG2, and K562 with IC50 values of 24.40, 28.86 and 38.75 µmol L-1, respectively.

The phytochemical investigation of the hexane extract which was obtained from the leaves of Xylopia laevigata (Annonaceae) produced six terpenes. Among these, five diterpenes named abieta-7,13-dien-3-one, ent-7β-acetoxy-16β-hydroxy-kaurane, 4-epi-cupressic acid, powerol, and labdorffianic acid B, and one oxygenated sesquiterpene, spathulenol. This is the first time these isolated diterpenes from X. laevigata have been described. The different structures belong to the abietane, kaurane, and labdane diterpenoids, and are indicative of the chemical diversity found in X. laevigata. Moreover, the diterpene ent-7β-acetoxy-16β-hydroxy-kaurane is reported herein for the first time as a natural product, and 4-epi-cupressic acid, powerol, and labdorffianic acid B are reported for the first time in the Annonaceae family. The structures of the isolated compounds were established by extensive analyses using 1D and 2D NMR spectroscopy in combination with MS. The cytotoxic activities of compounds abieta-7,13-dien-3-one, spathulenol, 4-epi-cupressic acid, and powerol were evaluated against tumor and non-tumor cell lines, in which spathulenol was found to be the most active, mainly against K562 with an IC50 value of 17.20 μmol L-1. (Annonaceae terpenes abieta7,13dien3one, abieta713dien3one abietadienone abieta 7,13 dien 3 one, 7 13 abieta-7,13-dien-3-one ent7βacetoxy16βhydroxykaurane, ent7βacetoxy16βhydroxykaurane entβacetoxyβhydroxykaurane ent 7β acetoxy 16β hydroxy kaurane β 4epicupressic epicupressic 4 epi cupressic sesquiterpene X described abietane diterpenoids Moreover product family D MS nontumor non lines active K K56 IC IC5 1720 17 20 17.2 L1. L1 L 1. 1 L-1 abieta7 13dien3one abieta7,13dien3one 713 7,1 βacetoxy βhydroxykaurane K5 172 2 17. L- dienone 71 7,

The methodology developed in this study through the acquisition of fingerprint chromatograms by liquid chromatography-diode array detector (LC-DAD), aided by principal component analysis, made it possible to assess, in a rational way, the chemical differences between six accessions of Lippia alba and to verify the influence of the method of extraction, the seasonality and the individuality of each accession on chemical composition of its extracts. Among all extracts analyzed against cancer cell lines, eight of them showed to be more promising against a human leukemia cell line (HL-60), displaying cell growth inhibition percentage ranging between 40.0 and 52.0%. In the inhibitory activity assays against acetylcholinesterase enzyme, all extracts showed weak inhibitory effect, with highlight only for six of them, which displayed inhibition ranging between 27.0 and 32.0%.

The phytochemical investigation of the alkaloid-rich fraction obtained from the leaves of Guatteria pogonopus Mart. (Annonaceae) allowed the isolation and identification for the first time in this species of: (+)-nornuciferine (1), a mixture of 1 and (+)-anonaine (2), (+)-isocorydine (3), (+)-nuciferine (4), (+)-roemerine (5), (-)-tetrahydropseudocolumbamine (6), a mixture of 6, liriodenine (9) and lysicamine (10), a mixture of 1,2,9-trimethoxy-10-hydroxyaporphine (7) and bulbocapnine (8), 9, 10, and (+)-N-methyllindicarpine (11). Compounds 6, 7, 8, and 11 have not been previously reported in the family Annonaceae. Furthermore, the formerly synthetic 1,2,9-trimethoxyaporfin-10-ol (7) is described for the first time as a natural aporphine alkaloid herein. The chemical structures were established by 1D and 2D NMR as well as in comparison with data previously reported in the literature. The cytotoxic activity of the alkaloids was evaluated against tumor (B16-F10, HepG2, HL-60, and K562) and non-tumor (PBMC) cell lines. Alkaloid 1 presented significant activity against HepG2 cell lines with IC50 of 9.60 µmol L-1 while the mixture of 6, 9 and 10 displayed strong cytotoxic activity against HL-60 and K562 cell lines with IC50 values of 3.41 an 8.50 µmol L-1, respectively.

ABSTRACT Geopropolis is a special type of propolis produced by stingless bees. Several pharmacological properties have been described for different types of geopropolis, but there have been no previous studies of the geopropolis from Melipona mondury. In this study, we investigated the antioxidant, antibacterial, and antiproliferative activities of M. mondury geopropolis, and determined its chemical profile. The antioxidant activity was determined using in vitro ABTS·+, ·DPPH, and β-carotene/linoleic acid co-oxidation methods. The antibacterial activity was determined using a microdilution method with Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant S. aureus. The antiproliferative effect was determined in tumor cell lines using the Alamar Blue assay. The chemical profile was obtained using UHPLC-MS and UHPLC-MS/MS. The butanolic fraction had the highest concentration of phenolic compounds and more potent antioxidant properties in all assays. This fraction also had bacteriostatic and bactericidal effects against all bacterial strains at low concentrations, especially S. aureus. The hexane fraction had the highest antiproliferative potential, with IC50 values ranging from 24.2 to 46.6 µg/mL in HL-60 (human promyelocytic leukemia cell) and K562 (human chronic myelocytic leukemia cell), respectively. Preliminary chemical analysis indicates the presence of terpenes and gallic acid in the geopropolis. Our results indicate the therapeutic potential of geopropolis from M. mondury against inflammatory, oxidative, infectious, and neoplastic diseases.

Piplartine (PPTN) is an alkaloid amide found in Piper species that presents different activities. PPTN determination in rat plasma is necessary to better understand its biological effects. The aim of this study was to develop a sensitive LC-MS/MS method for the determination of PPTN in rat plasma. The performance criteria for linearity, sensitivity, precision, accuracy, recovery, and stability have been assessed and were within the recommended guidelines. The validated method proved to be suitable in a pilot study of PPTN kinetic disposition in rat plasma after a single intraperitoneal dose, and represents an appropriate tool to further pharmacokinetic studies.