Electromyographic characteristics of pelvic floor muscles in women with stress urinary incontinence following sEMG-assisted biofeedback training and Pilates exercises.

The aim of this study was to compare the effect of pelvic floor muscle training with surface electromyographic (sEMG) biofeedback (BF group) and Pilates exercises (P group) on the bioelectrical activity of pelvic floor muscles in women with stress urinary incontinence. The other aim aim was to compare changes in voiding diaries and scores on quality of life questionnaire against baseline values and between the groups. Women in the BF group (n = 18) participated in pelvic floor muscle training with sEMG biofeedback; the P group (n = 13) participated in basic level Pilates workouts. Both protocols were continued for eight weeks. Voiding diary, quality of life and electromyographic characteristics of the pelvic floor muscles were assessed at the three-time points: at baseline, after eight weeks' training, and at month six post-training. The sEMG activity of the pelvic floor muscles was tested during five trials in two positions. There was no marked improvement in bioelectrical activity of the pelvic floor muscles during contraction following training with sEMG biofeedback or Pilates exercises. Following eight weeks of sEMG biofeedback training, a decrease was noted in resting bioelectrical activity of pelvic floor muscles and during relaxation after sustained contraction but only in supine-lying. No such effect was observed in the Pilates group. In the BF group, the number of incontinence episodes after end of treatment (timpepoints: 1vs. 2) and at six month follow-up (timpepoints: 1vs. 3) decreased by 68.5% and 89.3%, respectively. The respective values in the P group were 78.6%, and 86.4%. The intergroup differences did not reach the level of statistical significance. As regards the quality of life, the questionnaire demonstrated that Pilates exercises had significantly better effects compared to biofeedback training both at the end of the eight-week exercise program and (p = 0.003) and at six month follow-up (p = 0.0009). The International Consultation on Incontinence Questionnaire-Short Form (ICIQ- SF) showed comparable efficacy of Pilates exercises and training with sEMG biofeedback. Intragroup improvements in micturition frequency, incontinence (leakage) episodes, and nocturia frequency were comparable. Alleviation of urinary incontinence symptoms was comparable in both groups, whereas the improvement in the quality of life was more notable in the Pilates group. The obtained results failed to demonstrate the superiority of any of the two methods regarding the bioelectrical activity of pelvic floor muscles in patients with stress urinary incontinence.

Synthesis, Antibacterial, and Anticancer Evaluation of Novel Spiramycin-Like Conjugates Containing C(5) Triazole Arm.

Huisgen cycloaddition allowed obtaining of novel triazole-bridged antibiotics (6-16) with the reconstructed C(5) arm of spiramycin. (1)H-(1)H NOESY couplings indicated the structure of novel derivatives in solution and demonstrated that the rebuilt C(5) arm is slightly differently oriented relative to the aglycone part if compared to that of spiramycin (1). Combined analysis of biological data together with experimentally determined lipophilicity (clogP) and solubility show the importance of the chemical nature of the newly introduced triazole C(5) arm in the presence of attractive antibacterial and anticancer potency. The most cytotoxic active triazole conjugates having a hydrophobic and bulky C(5) arm showed higher selectivity toward cancer cell lines (HeLa, KB, MCF-7, Hep-G2, and U87) relative to HDF normal cells than that of the parent spiramycin. Our studies have demonstrated that the aldehyde group is not crucial for the presence of interesting antibacterial [MIC(S. pneumoniae) ∼ 1.2 µM] and anticancer [IC50(HepG2) ∼ 6 µM] properties of 16-membered lactone macrolides based on spiramycin's aglycone.

Synthesis, structure and antimicrobial evaluation of a new gossypol triazole conjugates functionalized with aliphatic chains and benzyloxy groups.

Synthetic limitations in the copper-catalyzed azide alkyne cycloaddition (CuAAC) on gossypol's skeleton functionalized with alkyne (2) or azide (3) groups have been indicated. Modified approach to the synthesis of new gossypol-triazole conjugates yielded new compounds (24-31) being potential fungicides. Spectroscopic studies of triazole conjugates 24-31 have revealed their structures in solution, i.e., the presence of enamine-enamine tautomeric forms and π-π stacking intramolecular interactions between triazole arms. Biological evaluation of the new gossypol-triazole conjugates revealed the potency of 30 and 31 derivatives, having triazole-benzyloxy moieties, comparable with that of miconazole against Fusarium oxysporum. The results of HPLC evaluation of ergosterol content in different fungi strains upon treatment of gossypol and its derivatives enabled to propose a mechanism of antifungal activity of these compounds.

Regio- and Stereoselective Functionalization of 16-Membered Lactone Aglycone of Spiramycin via Cascade Strategy.

Functionalization of 16-membered aglycone of spiramycin with the use of intramolecular cascade strategy yielded access to novel types of diastereopure bicyclic spiramycin derivatives containing tetrahydrofuran ring. Experimental results shows that a specific sequence of regio- and stereoselective transformations, based on the intramolecular transesterification, E1cB tandem eliminations, 1,2-addition to carbonyl, and 1,6-conjugate addition at the spiramycin aglycone, proceeds with the inversion of absolute configuration at C(5) stereogenic center. Performed cascade and multistep transformations have opened new possibilities in divergent modifications, not only spiramycin but also the whole family of leucomycin type antibiotics having a similar structure of 16-membered aglycone lactone ring.

Structure and evaluation of antibacterial and antitubercular properties of new basic and heterocyclic 3-formylrifamycin SV derivatives obtained via 'click chemistry' approach.

Thirty four novel derivatives of 3-formylrifamycin SV were synthesized via reductive alkylation and copper(I)-catalysed azide-alkyne cycloaddition. According to the obtained results, 'click chemistry' can be successfully applied for modification of structurally complex antibiotics such as rifamycins, with the formation of desired 1,2,3-triazole products. However, when azide-alkyne cycloaddition on 3-formylrifamycin SV derivatives demanded higher amount of catalyst, lower temperature and longer reaction time because of the high volatility of substrates, an unexpected intramolecular condensation with the formation of 3,4-dihydrobenzo[g]quinazoline heterocyclic system took place. Structures of new derivatives in solution were determined using one- and two-dimensional NMR methods and FT-IR spectroscopy. Computational DFT and PM6 methods were employed to correlate their conformation and acid-base properties to biological activity and establish SAR of the novel compounds. Microbiological, physico-chemical (logP, solubility) and structural studies of newly synthesised rifamycins indicated that for the presence of relatively high antibacterial (MIC ~0.01 nmol/mL) and antitubercular (MIC ~0.006 nmol/mL) activities, a rigid and basic substituent at C(3) arm, containing a protonated nitrogen atom "open" toward intermolecular interactions, is required.

13C and 15N CP/MAS, 1H-15N SCT CP/MAS and FTIR spectroscopy as tools for qualitative detection of the presence of zwitterionic and non-ionic forms of ansa-macrolide 3-formylrifamycin SV and its derivatives in solid state.

(13)C, (15)N CP/MAS, including (1)H-(13)C and (1)H-(15)N short contact time CP/MAS experiments, and FTIR methods were applied for detailed structural characterization of ansa-macrolides as 3-formylrifamycin SV (1) and its derivatives (2-6) in crystal and in powder forms. Although HPLC chromatograms for 2/CH3 OH and 2/CH3 CCl3 were the same for rifampicin crystals dissolved in respective solvents, the UV-vis data recorded for them were different in 300-375 nm region. Detailed solid state (13)C and (15)N CP/MAS NMR and FTIR studies revealed that rifampicin (2), in contrast to 3-formylrifamycin SV (1) and its amino derivatives (3-6), can occur in pure non-ionic or zwitterionic forms in crystal and in pure these forms or a mixture of them in a powder. Multinuclear CP/MAS and FTIR studies demonstrated also that 3-6 derivatives were present exclusively in pure zwitterionic forms, both in powder and in crystal. On the basis of the solid state NMR and FTIR studies, two conformers of 3-formylrifamycin SV were detected in powder form due to the different orientations of carbonyl group of amide moiety. The PM6 molecular modeling at the semi-empirical level of theory, allowed visualization the most energetically favorable non-ionic and zwitterionic forms of 1-6 antibiotics, strongly stabilized via intramolecular H-bonds. FTIR studies indicated that the originally adopted forms of these type antibiotics in crystal or in powder are stable in standard laboratory conditions in time. The results presented point to the fact that because of a possible presence of two forms of rifampicin (compound 2), quantification of the content of this antibiotic in relevant pharmaceuticals needs caution.

A new model of binding of rifampicin and its amino analogues as zwitterions to bacterial RNA polymerase.

Seven new benzyl (3-9) and four new phenethyl (10-13) amino analogues of ansa-macrolide rifampicin (1) were synthesized using the optimised method of reductive amination. Structures of 3-13 in solution were determined by 1D and 2D NMR and FT-IR methods whereas the energetically most favoured conformation of amino analogues was calculated with the use of the PM5 method. Spectroscopic and semi-empirical studies revealed the presence of zwitterionic forms of all 3-13 analogues in solutions containing water traces. (1)H-(15)N HSQC and (1)H-(15)N HMBC in combination with (1)H-(1)H COSY and (1)H-(13)C HMBC two dimensional spectroscopic methods unambiguously evidenced that the presence of the zwitterionic form of ansa-macrolides was a consequence of proton transfer from the O(8)-H phenolic group to the secondary amine moiety within 3-13 structures. (1)H-(1)H NOESY studies indicated two different orientations of the substituent introduced at the C(3) position for benzyl and phenethyl amino analogues of rifampicin and their similar conformation within the ansa-bridges in solution. FT-IR studies of the deprotonation of molecule and comparison of these data with those for indicated 3-13 C(8)=O double bond character after formation of zwitterions in solution. Results of an antibacterial test against Gram-(-) and Gram-(+) strains were compared with detailed structural information on new analogues of 3-13 to indicate some structure-activity relationships. Molecular recognition studies of 1 and 12 inhibitors at the binding site of bacterial RNA polymerase (RNAP) as zwitterions revealed key intermolecular interactions and led to the proposition of a new model of RNAP inhibition, which explains significant differences in antibacterial properties of rifampicin and its analogues.