Synthesis and Characterization of cis-/trans-(±)-3-Alkyl-3,4-dihydro-6,7-dimethoxy-1-oxo-1H-isochromene-4-carboxylic Acids

A series of new 3-alkyl substituted cis- and trans-(±)-3,4-dihydro-6,7-dimethoxy-1-oxo-1H-isochromene-4-carboxylic acids (cis-/trans-1–3) was synthesized through the reaction of 6,7-dimethoxyhomophthalic anhydride with aliphatic aldehydes of varying chain lengths. Their structure and configuration were elucidated using spectral methods, including 1H, 13C, DEPT-135 NMR, FTIR, UV-Vis, and HRMS analyses. A deductive conformational analysis was performed for determining the preferred conformations in solution and to explain the observed vicinal coupling constants

Rational Design, Synthesis, and In Vitro Activity of Heterocyclic Gamma-Butyrobetaines as Potential Carnitine Acetyltransferase Inhibitors

This study investigates heterocyclic gamma-butyrobetaine (GBB) analogs as metabolic modulators through an integrated approach involving rational design, molecular docking, synthesis, and in vitro evaluation. The compounds synthesized demonstrated promising inhibitory potential toward carnitine acetyltransferase (CAT) and presumably other enzymes within the carnitine transferase family, with IC50 values ranging from 2.24 to 43.6 mM. Notably, some compounds demonstrated superior activity to the reference drug Meldonium (IC50 = 11.39 mM). A substantial outcome of the study that might serve as a foundation for future optimization and synthesis of more potent compounds was that a bulky, hydrophobic substituent at the gamma position enhances inhibitory activity, whereas esterification and increased polarity diminish it. The most effective compound was determined to be a reversible competitive inhibitor of CAT, with a Ki value of 3.5 mM comparable to Meldonium’s Ki of 1.63 mM. These results suggest that heterocyclic GBB analogs present potential candidates for regulating metabolic processes and treating conditions including ischemic diseases, diabetes, and specific cancers

<i>trans</i>-11-(3,4-Dimethoxyphenyl)-2,3,8,9-tetramethoxy-6-oxo-11,12-dihydro-6<i>H</i>-dibenzo[<i>c,h</i>]chromene-12-carboxylic Acid

The title compound, trans-11-(3,4-Dimethoxyphenyl)-2,3,8,9-tetramethoxy-6-oxo-11,12-dihydro-6H-dibenzo[c,h]chromene-12-carboxylic acid (4), was synthesized for the first time via a two-step protocol from 3,4-dimethoxyhomophthalic anhydride (1) and 3,4-dimethoxybenzaldehyde (DMBA). In the first step, 1 reacts with DMBA to give trans-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-1-oxo-3,4-dihydro-1H-2-benzopyran-4-carboxylic acid (2), which further reacts with two additional equivalents of 1 to give 4. Compound 4 was characterized by means of spectral methods—1H-, 13C-, DEPT-135-NMR, and HRMS

17&beta;-Hydroxy-2-oxa-5&alpha;-androstan-3-one

We have successfully synthesized a 2-oxa androstane derivative, 17&beta;-hydroxy-2-oxa-5&alpha;-androstan-3-one (6), and confirmed its structure using NMR spectroscopy and mass spectrometry

Echovirus 30 in Bulgaria during the European Upsurge of the Virus, 2017–2018

In 2018, an increase in echovirus 30 (E30) detections was reported in some European countries. To assess the circulation and phylogenetic relationships of E30 in Bulgaria, E30 samples identified at the National Reference Laboratory for Enteroviruses, National Centre of Infectious and Parasitic Diseases, Bulgaria (NRL for Enteroviruses) in 2017 and 2018 were subjected to sequencing and phylogenetic analysis. The present study revealed that sample positivity did not significantly increase in Bulgaria during the European upsurge. E30 was identified in six patients, two of whom were epidemiologically linked. The maximum-likelihood phylogenetic tree showed that sequences from five patients belonged to the G1 lineage (clades G1a and G1b). The sequence from one patient belonged to the G2 lineage and was grouped closer to sequences from the last E30 outbreak in Bulgaria in 2012. No recombination events were detected. The European E30 upsurge in 2018 was caused by two clades, and one of them was G1. The fact that the majority of the Bulgarian samples belonged to G1 indicated that the virus was present in the country but did not cause a local upsurge. Phylogenetic and epidemiological data indicated sporadic E30 cases and a possible shift towards G1 lineage in 2017 and 2018

Rhinovirus Genotypes Circulating in Bulgaria, 2018&ndash;2021

Rhinoviruses (RV) are one of the most common causative agents of respiratory infections, with significant socioeconomic impact. RV infections are not notifiable in Bulgaria, and little is known about the different RV genotypes circulating in the country. This study aims to investigate the diversity of RV genotypes that were circulating in Bulgaria in the period 2018&ndash;2021 in samples from ILI/ARI patients. Genotype assignment was based on sequencing and phylogenetic analysis of the 5&prime; untranslated region and the VP4-VP2 region. Out of a total of 1385 nasopharyngeal swabs tested, 166 were RV-positive (RV detection rate: 11.99% (166/1385)). Those with a cycle threshold &lt;25 were selected for genotyping (n = 63). RV isolates were successfully genotyped and classified into 34 genotypes within Rhinovirus A (RV-A), Rhinovirus B (RV-B) and Rhinovirus C (RV-C) species. Presumptive recombination events between the 5&prime;UTR and VP4-VP2 regions were detected in three of the isolates. RV-A and RV-C were the prevalent RV species, with significantly more frequent detections of RV-A in the years before the COVID-19 pandemic compared to the post-pandemic period, when RV-C prevailed. The present study is the first to determine RV genotypes in Bulgaria and the circulation of RV-C has been described for the first time in the country