New Flexible Analogues of 8-Aza-7-deazapurine Nucleosides as Potential Antibacterial Agents.

A variety of ribo-, 2'-deoxyribo-, and 5'-norcarbocyclic derivatives of the 8-aza-7-deazahypoxanthine fleximer scaffolds were designed, synthesized, and screened for antibacterial activity. Both chemical and chemoenzymatic methods of synthesis for the 8-aza-7-deazainosine fleximers were compared. In the case of the 8-aza-7-deazahypoxanthine fleximer, the transglycosylation reaction proceeded with the formation of side products. In the case of the protected fleximer base, 1-(4-benzyloxypyrimidin-5-yl)pyrazole, the reaction proceeded selectively with formation of only one product. However, both synthetic routes to realize the fleximer ribonucleoside (3) worked with equal efficiency. The new compounds, as well as some 8-aza-7-deazapurine nucleosides synthesized previously, were studied against Gram-positive and Gram-negative bacteria and M. tuberculosis. It was shown that 1-(ß-D-ribofuranosyl)-4-(2-aminopyridin-3-yl)pyrazole (19) and 1-(2',3',4'-trihydroxycyclopent-1'-yl)-4-(pyrimidin-4(3H)-on-5-yl)pyrazole (9) were able to inhibit the growth of M. smegmatis mc2 155 by 99% at concentrations (MIC99) of 50 and 13 µg/mL, respectively. Antimycobacterial activities were revealed for 4-(4-aminopyridin-3-yl)-1H-pyrazol (10) and 1-(4'-hydroxy-2'-cyclopenten-1'-yl)-4-(4-benzyloxypyrimidin-5-yl)pyrazole (6). At concentrations (MIC99) of 40 and 20 µg/mL, respectively, the compounds resulted in 99% inhibition of M. tuberculosis growth.

Left Ventricle Non-Compaction Myocardium and Thrombophilia in a Pregnant Woman.

Non-compaction of the ventricular myocardium (NCM) is a genetic cardiomyopathy usually due to mutationof the G4.5 gene located in the Xq28 chromosomal region. This congenital disorder is characterized by pronounced trabeculations and intertrabecular recesses resulting from abnormal embryogenesis between the fifth and eighth fetal weeks. The reported prevalence in the general population is between 0.014% and 1.3%. The classic triad of complications includes heart failure, ventricular arrhythmias and systemic embolic events, although some patients have an asymptomatic form. NCM is commonly diagnosed by echocardiography, but contrast ventriculography, CT and MRI can also be used. Here we present a case of left ventricle NCM, manifested after respiratory infection, in a pregnant patient with congenital thrombophilia and a history of myocardial infarction. LEARNING POINTS: Non-compaction myocardium (NCM) in pregnant women has been associated with a poor prognosis.We should avoid routinely recommending young women with NCM to refuse pregnancy.A decision to continue pregnancy should be made by the patient in discussion with specialists.