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The tropical tree Calophyllum brasiliense Cambess. (Clusiaceae) grows in rain forests from Brazil to Mexico. Its leaves, as well as those of other Calophyllum species, are rich sources of chromanone acids, such as apetalic acid, isoapetalic acid, and their derivatives. Apetalic acid has shown significant antimycobacterial activity. The biological activity of apetalic acid has been related to the configuration of three asymmetric centers and the stereochemistry of the molecule; however, the C-19 configuration in the acidic side chain has not been fully resolved. For this reason, the unequivocal determination of the absolute configuration by means of X-ray crystallography in a sample of unique homogeneous apetalic acid stereoisomer was the most important point to start this study. Chiral amides were prepared using the carboxyl group. We determined the C-19 stereochemistry of apetalic acid and its specific chiral derivatives using NMR, X-ray diffraction, and molecular mechanics. Finally, we observed that steric hindrance in the side chain of apetalic acid leads to restriction of rotation around the pivotal linkage C-10-C-19, establishing chiral centers at C2(R), C3(S), and C19(R). We were able to separate the derivatives of these two high-rotatory-barrier conformers of apetalic acid by forming diastereoisomeric amides with phenylglycine methyl ester having a chiral center at C-2'. Our results confirmed the existence of atropisomerism in the apetalic acid molecule. Key words: NMR of apetalic acid chiral amides, absolute configuration and conformation, X-ray studies versus NMR, stable conformers of apetalic acid, high-rotatory-barrier conformers of apetalic acid. L'espece Calophyllum brasiliense Cambess. (Clusiaceae) est un arbre qui pousse dans les forets tropicales du Bresil jusqu'au Mexique. Ses feuilles, comme celles d'autres especes de Calophyllum, sont une source riche en acides de chromanone, tels que l'acide apetalique, l'acide isoapetalique et leurs derives. L'acide apetalique a montre une activite antimycobacterienne substantielle. Un lien a ete observe entre l'activite biologique de l'acide apetalique et la configuration de trois centres asymetriques ainsi que la stereochimie de la molecule. Cependant, la configuration du carbone C19 de la chaine laterale acide n'a pas ete completement resolue. Pour cette raison, la determination sans equivoque de la configuration absolue par radiocristallographie sur un echantillon d'un seul stereoisomere homogene d'acide apetalique a ete le motif le plus important pour entreprendre cette etude. Nous avons prepare des amides chiraux en utilisant le groupe carboxyle. Nous avons determine la stereochimie du carbone C19 de l'acide apetalique et de certains de ses derives chiraux au moyen de la RMN, de la diffraction des rayons X et de la mecanique moleculaire. Enfin, nous avons observe que l'encombrement sterique dans la chaine laterale de l'acide apetalique entraine une restriction de rotation autour de la liaison C10-C19, qui determine la stereochimie des centres chiraux aux positions C2(R), C3(S) et C19(R). Nous sommes parvenus a separer les derives de ces deux conformeres a barriere de rotation elevee de l'acide apetalique en formant des amides diastereoisomeriques avec l'ester methylique de la phenylglycine qui possedent un centre chiral a la position C2'. Nos resultats confirment l'existence d'atropisomerisme dans la molecule d'acide apetalique. Mots-cles : RMN d'amides chiraux de l'acide apetalique, configuration absolue et conformation, etudes par rayons X versus RMN, conformeres stables de l'acide apetalique, conformeres a barriere de rotation elevee de l'acide apetalique., Introduction The Calophyllum genus (Clusiaceae) is composed of approximately 200 tree species with a pantropical distribution. (1,2) Most of them thrive within the Indo-Pacific zone, particularly from the Malay Peninsula [...]

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases. [ABSTRACT FROM AUTHOR]

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The propolis produced by bees are used in alternative medicine for treating inflammation, and infections, presumably due to its antioxidant properties. In this context, five propolis from México were investigated to determine their inhibitory lipid peroxidation properties. The ethyl acetate extract from a red propolis from Chiapas State (4-EAEP) was the most potent (IC50 = 1.42 ± 0.07 μg/mL) in the TBARS assay, and selected for further studies. This extract afforded two new compounds, epoxypinocembrin chalcone (6), and an ε-caprolactone derivative (10), as well as pinostrobin (1), izalpinin (2), cinnamic acid (3), pinocembrin (4), kaempherol (5), 3,3-dimethylallyl caffeate in mixture with isopent-3-enyl caffeate (7a + 7b), 3,4-dimethoxycinnamic acid (8), rhamnetin (9) and caffeic acid (11). The HPLC profile, anti-mycobacterial, and antioxidant properties of this extract was also determined. Most of the isolated compounds were also tested by inhibition of reactive oxygen species (ROS) in challenged mouse bone marrow-derived mast cells (BMMCs), and DPPH. Their anti-inflammatory activity was evaluated by TPA, and MPO (myeloperoxidase) activity by ear edema test in mice. The most potent compounds were 7a + 7b in the TBARS assay (IC50 = 0.49 ± 0.06 μM), and 2 which restored the ROS baseline (3.5 μM). Our results indicate that 4-EAEP has anti-oxidant, and anti-inflammatory properties due to its active compounds, suggesting it has anti-allergy and anti-asthma potential. [ABSTRACT FROM AUTHOR]

Background: Reactive oxygen species (ROS) are important mediators in a number of degenerative diseases. Oxidative stress refers to the imbalance between the production of ROS and the ability to scavenge these species through endogenous antioxidant systems. Since antioxidants can inhibit oxidative processes, it becomes relevant to describe natural compounds with antioxidant properties which may be designed as therapies to decrease oxidative damage and stimulate endogenous cytoprotective systems. The present study tested the protective effect of two xanthones isolated from the heartwood of Calophyllum brasilienses against FeSO4- induced toxicity. Methods: Through combinatory chemistry assays, we evaluated the superoxide (O2●—), hydroxyl radical (OH●), hydrogen peroxide (H2O2) and peroxynitrite (ONOO—) scavenging capacity of jacareubin (xanthone III) and 2-(3,3-dimethylallyl)-1,3,5,6-tetrahydroxyxanthone (xanthone V). The effect of these xanthones on murine DNA and bovine serum albumin degradation induced by an OH• generator system was also evaluated. Additionally, we investigated the effect of these xanthones on ROS production, lipid peroxidation and glutathione reductase (GR) activity in FeSO4-exposed brain, liver and lung rat homogenates. Results: Xanthone V exhibited a better scavenging capacity for O2●—, ONOO- and OH● than xanthone III, although both xanthones were unable to trap H2O2. Additionally, xanthones III and V prevented the albumin and DNA degradation induced by the OH● generator system. Lipid peroxidation and ROS production evoked by FeSO4 were decreased by both xanthones in all tissues tested. Xanthones III and V also prevented the GR activity depletion induced by prooxidant activity only in the brain. Conclusions: Altogether, the collected evidence suggests that xanthones can play a role as potential agents to attenuate the oxidative damage produced by different pro-oxidants. [ABSTRACT FROM AUTHOR]

The structure and stereochemistry of four sesquiterpene lactones, budlein A (1), zaluzanin A (2), and glaucolides D (3a) and E (3b), isolated from Mexican Asteraceae species, for which only partial NMR data could be found in the literature, were determined. A combination of 1D and 2D high-resolution NMR experiments, such as DEPT, COSY, NOESY, ROESY, HMQC, HSQC, and HMBC, were used to completely assign the 1H and 13C spectra. The crystal structures of zaluzanin A (2) and glaucolide E (3b) were also determined. Glaucolides D and E have been previously reported to relax KCl-induced contraction in rat uterine smooth muscle; therefore, the effects of zaluzanin A and budlein A were examined in the same model. It was found that both compounds can relax contraction induced by KCl, but only zaluzanin A induced relaxation when contraction was induced with oxytocin. The preliminary biological test results according to these profiles are reported in this paper.Key words: NMR data, X-ray data, sesquiterpene lactones, Mexican Asteraceae, smooth muscle relaxant. On a déterminé la structure et la stéréochimie de quatre lactones sesquiterpéniques, la budléine A (1), la zaluzanine A (2), et les glaucolides D (3a) et E (3b), isolées d’espèces mexicaines d’Asteraceae, pour lesquelles seulement des données de RMN partielles ont pu être trouvées dans la littérature. On a utilisé une combinaison d’expériences de RMN à haute résolution 1D et 2D, telles que DEPT, COSY, NOESY, ROESY, HMQC, HSQC et HMBC, pour assigner complètement les spectres de 1H et 13C. On a aussi déterminé la structure cristalline de la zaluzanine A (2) et du glaucolide E (3b). Précédemment, on avait rapporté que les glaucolides D et E relaxent la contraction induite par le KCl dans le muscle utérin lisse de rate; en conséquence, on a examiné les effets de la zaluzanine A et de la budléine A dans le même modèle. On a trouvé que les deux composés peuvent relaxer la contraction induite par le KCl, mais que seule la zaluzanine A induit la relaxation quand la contraction est induite avec l’ocytocine. On présente les résultats préliminaires des tests biologiques appropriés dans cet article.Mots-clés : données de RMN, données de rayons-X, lactones sesquiterpéniques, Asteraceae du Mexique, relaxant du muscle lisse. [ABSTRACT FROM AUTHOR]