Activity of Compounds from Temperate Propolis against Trypanosoma brucei and Leishmania mexicana

Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC₅₀ values < 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4′-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4′,7-dimethoxykaempferol, and naringenin 4′,7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities ≤ 15 µM. The most active compounds against T. brucei were naringenin 4′,7 dimethyl ether and 4′methoxy kaempferol with activity of 15–20 µM against the three T. brucei strains. The most active compounds against L. mexicana were 4′,7-dimethoxykaempferol and the coumaric acid ester mixture, with EC₅₀ values of 12.9 ± 3.7 µM and 13.1 ± 1.0 µM. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain; no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.     

Heteroannulation of 2-amino-6-thioxouracil: A new access for the synthesis of fused pyrimidine derivatives

In current work, heteroannulation of 2-amino-6-thioxouracil to new fused pyrimidine scaffolds is described, where pyrimidine 1 undergoes cyclocondensation with pyruvic acid derivative 2 and ninhydrin ( 6 ) to furnish thiopyranopyrimidine 5 and thienopyrimidine 8 , respectively. Alkylation of aminopyrimidine 1 with benzyl chloride consumed two moles to form S- and N-alkylated product 9 . Subjecting compound 9 to aminolysis with aniline derivatives resulted in 4-aminopyrimidine 10a , b through Dimorth rearrangement. Furthermore, the addition of cyclic enamine 10a , b to ninhydrin and benzoyl isothiocyanate produced pyrimidine derivatives 12a,b and 14 . Finally, the addition of enamenic carbon of 10a , b to polarized systems 2 or 18 afforded the pyrido[2,3-d]pyrimidines 17 and 21a-d in moderate to good yield.     

Phenolic constituents from Wissadula periplocifolia (L.) C. Presl. and anti-inflammatory activity of 7,4′-di-O-methylisoscutellarein

This study reports the first phenolics from Wissadula genus (Malvaceae) and the anti-inflammatory activity of 7,4′-di-O-methylisoscutellarein. Using chromatographic methods, five phenolic compounds were isolated from aerial parts of Wissadula periplocifolia (L.) C. Presl. The compounds were identified as 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, trans-cinnamic acid, tamgermanetin and 7,4′-di-O-methylisoscutellarein using spectroscopic methods. The flavone 7,4′-di-O-methylisoscutellarein showed anti-inflammatory activity by inhibiting neutrophils recruitment in a mice model of pleurisy and by decreasing significantly the production of cytokines IL-1β and TNF-α.     

Molecular Docking Study of Newly Synthesized Thiopyrimidines as Antimicrobial Agents Targeting DNA Gyrase Enzyme

A new series of thiopyrimidine‐5‐carbonitrile derivatives were synthesized and the chemical identity of them was established on the basis of spectral methods. The antimicrobial properties of all derivatives were investigated against Gram‐positive and Gram‐negative bacteria as well as fungal strains. The results of the antimicrobial screening showed that compounds 4 , 11 , and 12 have a higher and broad spectrum efficacy against all the tested organisms in comparison with the reference drugs. Interestingly, the most active compounds 4 and 12 showed good binding assay results with Escherichia coli DNA gyrase comparable to that of the reference, methotrexate. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, DNA gyrase.