Emerging Therapeutics:The imidazo[1,2-b]pyridazine scaffold as a novel drug candidate for eumycetoma, a neglected tropical disease

Mycetoma is a neglected invasive infection endemic in tropical and subtropical regions, presenting as a chronic subcutaneous inflammatory mass that can spread to deeper structures, leading to deformities, disabilities, and potentially mortality. The current treatment of eumycetoma, the fungal form of mycetoma, involves antifungal agents, such as itraconazole, combined with surgical intervention. However, this approach has limited success, with low cure rates and a high risk of recurrence. This study addresses to the urgent need for more effective therapeutics by designing and synthesising 47 diversely pharmacomodulated imidazo[1,2-b]pyridazine derivatives using a simple synthetic pathway with good yields and purity. Of these, 17 showed promising in vitro activity against Madurella mycetomatis, the prime causative agent of eumycetoma, with IC50 ≤ 5 μM and demonstrated significantly lower cytotoxicity compared to standard treatments in NIH-3T3 fibroblasts. Notably, compound 14d exhibited an excellent activity with an IC50 of 0.9 μM, in the same order then itraconazole (IC50 = 1.1 μM), and achieved a favourable selectivity index of 16 compared to 0.8 for itraconazole. These promising results warrant further research to evaluate the clinical potential of these novel compounds as safer, more effective treatments for eumycetoma, thus addressing a profound gap in current therapeutic strategies

Infections hivernales et Médecines complémentaires (Prévention par stimulation du système immunitaire)

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Natural Deep Eutectic Solvents as sustainable solvent for Suzuki-Miyaura cross- coupling reactions applied to imidazo-fused heterocycles

International audienc

Regiocontrolled functionalization of 2,3-dihalogenoimidazo[1,2-a] pyridines by Suzuki-Miyaura and Sonogashira cross-coupling reactions

International audienceAn efficient method for regiocontrolled functionalization of 2,3-dihalogenoimidazo[1,2-a] pyridine was developed. This sequence allowed the selective introduction of aryl, heteroaryl, alkyl and alkynyl substituents at both 2- and 3-positions, by using Suzuki-Miyaura and Sonogashira cross-coupling reactions. A library of compounds diversely substituted on 2- and 3-positions can be easily prepared from a common, stable and easily accessible starting material

Quality control of commercial cranberry products: HPTLC-densitometry a new deal

International audienceA fast quality control protocol based on reference BL-DMAC assay and High-performance thin-layer chromatography (HPTLC)-Densitometry was optimized for routine quality control of cranberry (Vaccinium macrocarpon) products. The sample preparation appeared as a key step to ensure a relevant comparison of products quality and biological data. Sequential solid/liquid extractions were required to fully extract polyphenols, regardless the extraction solvent chosen. The HPTLC-densitometry herein protocol used epicatechin, PAC-A2 and PAC-B2 as quality markers and densitometric measurements at 200 nm. The PAC-A2/Epicatechin ratio, obtained using HPTLC, appeared as an appropriate indicator of the quality of cranberry ingredient. Only two products, among the tested panel, exhibited a high quality cranberry-based ingredient using this criteria. UPLC-MS analyses coupled to multivariate analyses confirmed HPTLC-densitometry conclusions. This work highlighted the plural PAC composition of commercial products and the lack of standardization for cranberry-based products on the market, explaining the non-reproducibility of clinical trials

Solid/liquid extraction as key step for quality assessment of commercial cranberry products using HPTLC-densitometry

Poster Session Wednesday : Theme 5: Production and regulatory aspects of herbal preparationsSolid/liquid extraction as key step for quality assessment of commercial cranberry products using HPTLC-densitometry. 9. Joint Natural Products Conference 201

Cassia sieberiana root bark used in traditional medicine in Togo: Anthelmintic property against Haemonchus contortus and tannins composition

International audienceHelminth infections of livestock result in economic losses around the globe. The majority of the people in West Africa treats such infections with medicinal plants related to the local traditional medicine. In a previous ethnomedicinal survey carried out in the north of Togo, traditional healers frequently cited Cassia sieberiana DC to treat helminth infections. The aim of the present study was to validate the traditional application of C. sieberiana root bark as a dewormer and to analyse the metabolite composition in preparations with this activity. Two tannin-rich fractions (FrE14 and FrE15) obtained from ethyl acetate extract were submitted to UPLC-MS analysis. The anthelmintic activity of C. sieberiana extracts and tannins-rich fractions was investigated on the small ruminant parasite Haemonchus contortus using Larval Migration Inhibition tests. The ethyl acetate, butanol and aqueous extracts significantly disrupted larval migration of Haemonchus contortus L3 with inhibition of 30.3%, 22.2% and 26.5% respectively at 2.5 mg/mL, as compared to negative control. The two tannin-rich fractions, FrE14 and FrE15 presented larval migration inhibition of 6.5% and 20.7% respectively at the same concentration. From these two fractions, 28 flavan-3-ols were identified including 3 monomers (catechin, epicatechin and epiafzelechin), 22 dimers (7 homodimers and 15 heterodimers) as well as 3 newly described trimers consisting of (epi)afzelechin, (ent)cassiaflavan or (epi)guibourtidinol subunits

Domino 6-endo-dig Cyclization/Halogenation Reactions: Three-Component Synthesis of 1,3-Disubstituted 4-Haloimidazo[1,2-a:4,5-c′]dipyridines

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One-step preparative isolation of aristolochic acids by strong ion‐exchange centrifugal partition chromatography

Poster Session Monday : Theme 2: Sources of bioactive compoundsOne-step preparative isolation of aristolochic acids by strong ion‐exchange centrifugal partition chromatography. 9. Joint Natural Products Conference 201

Antioxidative and wound healing properties of Crateva adansonii DC

Leaves of Crateva adansonii DC, a small bush found in Togo, are widely used in traditional medicine to cure infectious abscess. Traditional healers harvest only young leaves and sprouts early in the morning in order to prepare their drugs. To validate this ancestral practice, we performed a phytochemical screening of various C. adansonii leaves samples collected in different places, at different time and at different ages. Using antioxidant activity as selection criteria, optimal extracts were obtained with sprout leaves, collected at 5:00 am in Djidjolé. Wound healing potential was then investigated for several extracts in vitro on keratinocytes stimulated by Staphylococcus aureus proteins. Anti-inflammatory activity was highlighted with flavonoids-rich extracts, especially against TNFa. Those results validate the traditional practices and the potential of C. adansonii as wound healing drug