Abstract: Chemical investigation of the leaves from Ageratina glabrata yielded four new thymol derivatives, namely: 10-Benzoyloxy-8,9-dehydro-6-hydroxythymol isobutyrate (4), 10-benzoyloxy-8,9-dehydro thymol (5), 10-benzoyloxythymol (6) and 10-benzoyloxy-6,8-dihydroxy-9-isobutyryloxythymol (7). In addition, (8S)-10-benzoyloxy-8,9-epoxy-6-hydroxythymol isobutyrate (1), together with other two already known thymol derivatives identified as: 10-benzoyloxy-8,9-epoxy-6-methoxythymol isobutyrate (2) and 10-benzoyloxy-8,9-epoxythymol isobutyrate (3). In this paper, we wish to publish the structures and complete assignments of ¹H and ¹³C NMR data of compounds 1 – 7, and the absolute configuration for compound 1, unambiguously established by single crystal X-ray diffraction, and evaluation of the Flack parameter. The in vitro antiprotozoal assay showed that compound 1 and its derivative 1a were the most potent antiamoebic and antigiardial compounds. Both compounds showed selectivity and good antiamoebic activity like emetine and metronidazole, respectively, two antiprotozoal drugs used as positive controls. In relation of anti-propulsive effect, compound 1 and 1a showed moderate inhibitory activity, their activities were comparable to quercetin and compound 9, respectively, two natural antipropulsive compounds used as positive controls. These data suggest that compound 1 may play an important role in antidiarrheal properties of Ageratina glabrata.

This review explores the unique structural and functional characteristics of natural products featuring highly oxygenated cyclobutane rings, with a specific focus on oxetane and 1,2-dioxetane motifs. It presents the structures and biological activities of compounds containing these rings, highlighting their contribution to molecular stability and pharmacological potency. Through detailed case studies and recent research findings, it has been demonstrated that these oxygen-rich rings enhance the molecular diversity and biological efficacy of natural products, potentially offering new avenues for drug development. Notably, these compounds are predominantly synthesized by microorganisms and can also be found in extracts from fungi, plants, and certain marine invertebrates. Compounds with oxetane and 1,2-dioxetane rings are primarily noted for their strong antineoplastic properties, among other biological activities. In contrast, most 1,2-dioxetanes exhibit potent antiprotozoal effects. It is important to note that 1,2-dioxetanes often serve as intermediate products in oxidation reactions, characterized by their instability and propensity to decompose into new compounds.

Folk medicine is widely used in Angola, even for human African trypanosomiasis (sleeping sickness) in spite of the fact that the reference treatment is available for free. Aiming to validate herbal remedies in use, we have selected nine medicinal plants and assessed their antitrypanosomal ac-tivity. 122 extracts were prepared using different plant parts and solvents. 15 extracts from seven different plants exhibited in vitro activity against Trypanosoma brucei rhodesiense bloodstream forms >70% at 20 µg/ml. The dichloromethane extract of Nymphaea lotus (leaves and leaflets) and the ethanolic extract of Brasenia schreberi (leaves) had IC50 values ≤10 µg/ml. These two aquatic plants are of particular interest. They are being co-applied in the form of a decoction of leaves because they are considered by local healers as male and female of the same species, the ethnotaxon “longa dia simbi”. Bioassay-guided fractionation led to the identification of eight active molecules: gallic acid (IC50 0.5 µg/ml), methyl gallate (IC50 1.1 µg/ml), 2,3,4,6-tetragalloyl-glucopyranoside, ethyl gallate (IC50 0.5µg/ml), 1,2,3,4,6-pentagalloyl-β-glucopyranoside (IC50 20µg/ml), gossypet-in-7-O-β-glucopyranoside (IC50 5.5µg/ml), and hypolaetin-7-O-glucoside (IC50 5.7µg/ml) in B. schreberi, and 5-[(8Z,11Z,14Z)-heptadeca-8,11,14-trienyl] resorcinol (IC50 5.3µg/ml) not described to date in N. lotus. Five of these active constituents were detected in the traditional preparation. This work provides the first evidence for the ethnomedicinal use of these plants in the management of sleeping sickness in Angola.