Sergio Ortiz

Background: Combination therapy is increasingly explored as an alternative approach to manage bacterial infections and limit the emergence of antibiotic resistance. Building on traditional medicinal knowledge, this study aimed to investigate the potential synergistic antibacterial effects between Krameria lappacea (Dombey) Burdet & B.B.Simpson root extracts and conventional antibiotics. Methods: Root extracts were prepared using supercritical fluid extraction with different proportions of ethanol as a co-solvent. Their in vitro antibacterial activity was evaluated against Gram-positive bacteria and their interactions with gentamicin and vancomycin were assessed using an agar dilution-based combination assay. The chemical composition of the extracts was characterized using HRMS/MS-based dereplication and molecular networking. To further investigate the compounds contributing to the observed activity, an MS-guided isolation strategy was applied to an independent K. lappacea extract, resulting in the purification of a major neolignan previously detected in the active KL5 extract, which was subsequently evaluated using broth microdilution assays. Results: The less polar extract KL5, enriched in neolignans, exhibited the strongest antibacterial activity, with MIC values ranging from 3 to 12 µg/mL against Gram-positive strains. In combination assays, KL5 exhibited synergistic or additive interactions with gentamicin depending on the bacterial strain, whereas no synergistic effect was observed with vancomycin. The isolated neolignan displayed antibacterial activity and showed an additive interaction with gentamicin against Staphylococcus spp. Conclusions: These findings support the potential of K. lappacea neolignan-rich extracts as antibiotic adjuvants. The activity of the isolated neolignan supports the contribution of this chemical class to the antibacterial properties of KL5, while the absence of synergy for the isolated compound suggests that additional constituents and/or multicomponent interactions may contribute to the effect observed for the whole extract.

Médecines traditionnelles, source de composés bioactifs : de l’enquête ethnobotanique à la pharmacomodulation: Ces travaux, divisés en deux parties, décrivent la recherche de composés bioactifs à partir de médecines traditionnelles, des enquêtes ethnobotaniques aux modifications structurales de métabolites dans le but d'accroître leurs activités. Dans un premier temps, 18 plantes médicinales utilisées par la communauté Taira d'Atacama (Calama, Chili) ont été sélectionnées et extraites. Les activités antibactérienne, anti-parasitaire, antioxydante, anti-inflammatoire et antiproliférative ont été évaluées. Une démarche bioguidée a ensuite été appliquée et a conduit à l'isolement, à partir des extraits les plus actifs, du benzofurane (+)-conocarpane de Krameria lappacea, possédant une CMI comprise entre 0,5 et 2 µg/mL vis-à-vis de bactéries Gram positif aérobies et anaérobies facultatives, et de l'acide mulinique d'Azorella atacamensis, inhibant la croissance de la souche de Plasmodium falciparum 3d7 avec une CI50 de 0.11 µg/mL. Le récepteur P2X7 est impliqué dans plusieurs pathologies inflammatoires. Les extraits d'espèces européennes traditionnellement indiquées contre l'inflammation ont été testés in vitro sur des macrophages stimulés par LPS. Des extraits de différentes Scrophularia ont montré, à des concentrations de 0,1 à 1 µg/mL, un effet antagoniste de 70 à 90% sur P2X7. L'analyse des données UPLC-MS a permis d'identifier les glycosides d'iridoïdes harpagoside et harpagide comme principaux responsables de l'activité constatée. En outre, une comparaison de la composition et des activités biologiques des fruits de Pistacia lentiscus de Grèce et d'Algérie mûrs et avant maturité a été effectuée. La déréplication par réseaux moléculaires a été couplée aux évaluations anti-oxydante, anti-inflammatoire et d'inhibition de la tyrosinase. Les esters d'acide gallique ont pu être définis comme des marqueurs des extraits méthanoliques, positivement corrélés au degré de maturité des fruits ainsi qu'aux activités biologiques. La seconde partie a été consacrée à la pharmacomodulation par hémisynthèse de méthoxyflavones et de lactones sesquiterpéniques en vue d'accroître leurs activités initiales cytotoxiques et anti-plasmodiales. L'artémétine et la 3'-O-méthyleupatorine ont été isolées par approche chimiotaxonomique de Pentzia monodiana (Asteraceae). Elles ont démontré une activité anti-plasmodiale in vitro modérée ainsi qu'une forte affinité pour l'hème, bloquant ainsi la formation d'hémozoïne. Ensuite, par isolement, synthèse et hémisynthèse, une chimiothèque de 33 flavones a été bâtie puis évaluée face aux même cibles. Le dérivé le plus prometteur, le pentaméthoxyquercétol, a inhibé la croissance des souches 3d7 and W2 de P. falciparum avec des CI50 respectives de 3,9 et 9,5 µM et réduit la formation d'hémozoïne de 42 %. Le kétopélénolide B obtenu de la même espèce végétale est une lactone sesquiterpène structuralement proche de l'agent cytotoxique bréfeldine A. Ce dernier, en bloquant l'interaction protéine-protéine Arf1-Big1Sec7, essentielle à la progression tumorale et à la formation de vésicules, inhibe la croissance de lignées cancéreuses agressives. Parmi les 13 dérivés du kétopélénolide B hémisynthétisés, le 3-éthoxyimin-kétopélénolide B a démontré une activité inhibitrice du système Arf1-Big1Sec7 de 32 % à une concentration de 50µM supérieure à celle du produit naturel de départ (12 %) et proche de celle de la bréfeldine A. Les évaluations anti-prolifératives in vitro de toute la chimiothèque vis-à-vis de plusieurs lignées de cellules cancéreuses est en cours.

This study evaluated the phytochemical composition, antimicrobial activity, and in vivo protective effects of the hydroethanolic extract from Commiphora leptophloeos stem bark (HECL) against 5‐fluorouracil (5‐FU)‐induced intestinal mucositis. Despite the extensive traditional use of C. leptophloeos in gastrointestinal disorders, its stem bark extract has not yet been chemically characterized nor systematically investigated in experimental models of chemotherapy‐induced intestinal injury. Phytochemical analysis by mass spectrometry identified 21 metabolites, mainly procyanidins and flavonoids. Antimicrobial screening against 90 bacterial strains showed selective inhibition of Gram‐positive bacteria at 40–80 µg/mL. In vivo, mucositis was induced in female Swiss mice with 5‐FU (450 mg/kg, i.p.). Treatment with HECL (10 mg/kg) significantly preserved villus and crypt architecture ( p < 0.05) and reduced IL‐6 levels ( p < 0.05). HECL also increased MUC‐2 expression ( p < 0.05), while maintaining intestinal barrier integrity, as indicated by occludin immunostaining. Additionally, the extract modulated oxidative stress (malondialdehyde) and acetylcholinesterase activity. Overall, HECL demonstrated bioactive potential with broad‐spectrum antimicrobial activity and protective effects against chemotherapy‐induced intestinal injury, supporting its role as a therapeutic adjuvant in intestinal disorders.

Antimicrobial resistance (AMR) remains a major threat to modern medicine, fueled by the excessive use of antibiotics and the spread of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). In this study, we designed and synthesized a series of 2-aryl-4-aminoquinazoline derivatives bearing an aminoalkylimidazole linker, combining two pharmacophoric motifs associated with antimicrobial activity. Starting from anthranilamide, the compounds were prepared in three straightforward steps, affording good yields and high purity. Their structures were confirmed by FT-IR spectroscopy, ¹H and ¹³C nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). Biological evaluation showed that series 5 exhibited strong selectivity toward S. aureus, with compounds 5c and 5d displaying minimum inhibitory concentrations (MICs) between 2.2 and 4.4 µM. No significant activity was observed against other tested strains. Cytotoxicity assays in HepG2 cells revealed moderate to low inhibition. Molecular docking indicated preferential binding to dihydrofolate reductase (DHFR) and relevant interactions with topoisomerase IV, resembling reference inhibitors. ADME analysis predicted favourable absorption, blood–brain barrier permeability, and compliance with Lipinski’s rules.

From an endophytic strain of Cophinforma mamane isolated from the leaves of Bixa orellana, a previously undescribed γ-butyrolactone compound (2) and three new cyclopentapeptides (3-5) have been isolated from the same strain, along with the known (4R)-striatisporolide A (1). Their structures were elucidated through extensive spectral analysis and DP4+ calculations. The two γ-butyrolactone derivatives (1, 2) exhibited moderate inhibitory activity against axenic Leishmania infantum amastigotes (IC₅₀ = 13.33 and 4.43 μM, respectively), while only compound 2 displayed cytotoxic activity on Jurkat cells (17% growth inhibition at 1 μg/mL) and weak antibacterial activity against Enterococcus faecalis (MIC = 64 μg/mL).

Malaria remains a significant public health challenge in Niger, accounting for 5.6% of global malaria‐related deaths. Local medicinal plants are frequently used as traditional treatments for malaria, although their efficacy and safety are often insufficiently investigated. This study aims to evaluate the antiplasmodial activity and chemical composition of eight medicinal plants from Niger. Plant extracts were tested in vitro for their ability to inhibit the uptake of [ ³ H]‐hypoxanthine in the Plasmodium falciparum NF54 chloroquine‐sensitive strain. The most active extract was subjected to chemical analysis using HPLC–PDA–HRMS/MS dereplication, whereas major compounds were quantified via a validated LC–UV method. The ethyl acetate extract of Combretum aculeatum ( 2a ) demonstrated important antiplasmodial activity, with an IC ₅₀ value of 3.1 µg/mL and a selectivity index of 24.5. C ‐glycosyl flavonoids were identified as the primary constituents, present at concentrations ranging from 5.7 to 9.8 mg of vitexin equivalent per g of extract. However, the low abundance of these compounds suggests that other constituents may contribute to the extract's antiplasmodial effects. Further investigations are required to explore possible synergies among the components of 2a and to assess its efficacy in vivo models.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor–acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.