Delia Deidda

Importance of the thiomorpholine introduction in new pyrrole derivatives as antimycobacterial agents analogues of BM 212

During the course of our investigations in the field of azole antimicrobial agents, we have identified BM 212, a pyrrole derivative with good in vitro activity against mycobacteria and candidae. These findings prompted us to prepare new pyrrole derivatives 1-10 in the hope of increasing the activity. The microbiological data showed interesting in vitro activity against Mycobacterium tuberculosis and atypical mycobacteria.

New pyrrole derivatives as antimycobacterial agents analogs of BM212

During the course of our investigations in the field of azole antimicrobial agents, we have identified BM212 a pyrrole derivative with good in vitro activity against mycobacteria and candidae. These findings prompted us to prepare new pyrrole derivatives 2-6 in the hope of increasing the activity. The microbiological data showed interesting in vitro activity against Mycobacterium tuberculosis and atypical mycobacteria.

Pyrrolnitrin and related pyrroles endowed with antibacterial activities against Mycobacterium tuberculosis

During development of nitroheterocycles with potential antimycobacterial activities we have tested against Mycobacterium tuberculosis a number of pyrroles strictly related to pyrrolnitrin, an antifungal antibiotic isolated from Streptomyces pyrrocinia. Some of the tested arylpyrrole derivatives and pyrrolnitrin have shown appreciable inhibiting activity against M. tuberculosis and M. avium. SAR studies well correlate antimycobacterial potency with the presence of halogens in the phenyl ring and a nitro group at position 3 of pyrrole.

Chemical and biological comparisons on supercritical extracts of Tanacetum cinerariifolium (Trevir) Sch. Bip. with three related species of chrysanthemums of Sardinia (Italy)

In this manuscript, the authors compare the chemical composition and the biological effects of extracts of some Sardinian plant species: Glebionis coronaria (L.) Spach [=Chrysanthemum coronarium L.], locally known as ‘caragantzu’, Glebionis segetum (L.) Fourr. [=Chrysanthemum segetum L.], known as ‘caragantzu masedu’, and Sardinian endemic species Plagius flosculosus (L.) Alavi and Heywood [=Chrysanthemum flosculosus L.], known as ‘caragantzu burdu’. In addition, the authors compare the pyrethrins contained in these species with an extract of Tanacetum cinerariifolium (Trevir.) Sch. Bip. [=Chrysanthemum cinerariifolium (Trevir.) Vis.], a commercial species rich in pyrethrins. The volatile fractions from chrysanthemum flowers were obtained by supercritical fluid extraction (SFE) with CO2 at 90 bar and 50°C and by hydrodistillation. Pyrethrins were extracted, together with other high molecular mass compounds, by SFE at high pressure, 300 bar and 40°C. The composition of the volatile oils is determined by GC–MS analysis and the amount of pyrethrins by HPLC analysis. Moreover, the antibacterial and antimycotic activities of volatile fractions were investigated in order to compare to their traditional uses.

Ligand-based virtual screening, parallel solution-phase and microwave-assisted synthesis as tools to identify and synthesize new inhibitors of mycobacterium tuberculosis.

In an attempt to identify new inhibitors of the growth of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, a procedure for the generation, design, and screening of a ligand‐based virtual library was applied. This used both an in silico protocol centered on a recursive partitioning (RP) model described herein, and a pharmacophoric model for antitubercular agents previously generated by our research group. Two candidates emerged from databases of commercially available compounds, both characterized by a minimum inhibitory concentration (MIC) of 25 μg mL−1. Based on these compounds, two series of derivatives were synthesized by both parallel solution‐phase and microwave‐assisted synthesis, leading to enhanced antimycobacterial activity. During both the design and synthesis, attention was focused on the efficient allocation of available resources with the aim of reducing the overall costs associated with calculation and synthesis.

Extraction of Santolina insularis essential oil by supercritical carbon dioxide : influence of some process parameters and biological activity

Santolina insularis was used to obtain its essential oil by means of supercritical fluid extraction with carbon dioxide, CO2. The choice of the proper value of CO2 density is the crucial point influencing solvent power and selectivity, the main factors determining oil composition. In circuit to obtain a pure essential oil deprived of cuticular waxes, the extraction products were fractionated in two separators operated in series. A good process performance was obtained working at 90 bar and 50 °C in the extraction vessel, at 90 bar and −12 °C in the first separator and at 20 bar and 15 °C in the second separator. The extraction time proved to be another parameter that determines the composition of the essential oil extracted. Indeed, lower molecular weight and less polar compounds were more readily extracted, since the other families of compounds exhibit higher diffusion times. The oil extracted also contained small quantities of water. The water yield was measured and the possible role of water in the extraction process is discussed. A comparison with the oil obtained by hydrodistillation is also given. Finally, the cytotoxic and antimicrobial activity of the various extracts has been assayed. Copyright

New Trends in Development of Antimycobacterial Compounds

The resurgence of tuberculosis and the surge of multidrug-resistant clinical isolates of Mycobacterium tuberculosis have reaffirmed tuberculosis as a primary public health concern. In this review we describe some new findings on the pharmacological status of fluoroquinolones derivatives (Gatifloxacin, Moxifloxacin and Sitafloxacin), new macrolides (Clarithromycin, Azithromycin and Roxithromycin), new rifamycin derivatives (Rifapentin, Rifabutin and Rifalazil) and new oxazolidinones (Linezolid and PNU 100480). We describe also other type of agents that are being developed as antimycobacterial drugs. Some of these are under clinical investigation, while others are considered to be promising candidates for future development. Among them, nitroimidazopyrans, new ketolides, Isoxyl (ISO), pyrroles derived from BM 212, Mefloquine and Diarylquinoline R207910 are discussed. We also describe the mechanism of drug resistance in mycobacteria, as well as new potential targets.

Enhancement of anti-herpetic activity of glycyrrhizic acid by physiological proteins

Some enzymes present in biological fluids, such as lysozyme (LYS) and lactoferrin (LAC), are known to possess antibacterial and antiviral activity, against herpesviruses in particular. It will be shown in this paper that their combination with a natural triterpene, namely glycyrrhizic acid (GLA), gives significant results in enhancing the antagonistic activity on HSV1 in in vitro assays. Data elaboration was carried out by calculation of the FIC index (fractional inhibitory concentration) for each combination of the three compounds and by a three-dimensional evaluation of the inhibiting combinatory effects, which indicated the percentage of the synergistic action. A FIC index equal to or below 0.5 demonstrated a significant synergistic effect between two substances. Considering each single compound, the 50% inhibiting doses on viral replication (ID50) were 252±53 μg/ml for LAC, 497±165 μg/ml for LYS and 740±125 μg/ml for GLA. The combination of LAC and GLA showed a clear synergistic effect, with a FIC index of 0.08 and a potentiating activity which, for some doses, was up to 1.5 log10 of difference (from about 5.5×106 to 105 pfu/ml). The combinations of GLA and LYS, and LYS and LAC showed a less significant synergistic activity. These findings led to the conclusion that some physiological proteins, even at concentrations usually present in some body fluids, may enhance the anti-herpetic activity of a natural compound such as GLA.

Phenolic constituents from Ephedra Nebrodensis

Two new phenolic glycosides, 4-hydroxy-3-(3-methyl-2-butenyl)phenyl β-D-glucopyranoside (nebrodenside A) and O-coumaric acid β-D-allopyranoside (nebrodenside B), were isolated from the aerial parts of Ephedra nebrodensis. In addition, O-coumaric acid glucoside, (−)-epicatechin, and (−)-ephedrine were also isolated. The structures were deduced from extensive 1D and 2D NMR spectroscopy (1H, 13C, DQF-COSY, TOCSY, GHSQC, GHMQC, ROESY) as well as mass spectrometry (EI and HR-MALDI). (−)-Epicatechin showed weak antiviral activity against Influenza A virus and very weak cytotoxicity against MDCK cells.

N-[4-(1,1′-biphenyl)methyl]-4-(4-thiomorpholinylmethyl) benzenamines as non-oxazolidinone analogues of antimycobacterial U-100480

Thiomorpholine analogues of U-100480 with the biphenylmethyl group replacing the acetamidomethyloxazolidinone moiety have been synthesized and tested as antimycobacterial agents together with various related derivatives. Some biphenyl derivatives were endowed with high activity against Mycobacterium tuberculosis and other non-tuberculous mycobacteria.