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A novel series of phthalimide-dithiocarbamate hybrids was synthesized and evaluated for in vitro inhibitory potentials against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The anti-cholinesterase results indicated that among the synthesized compounds, the compounds 7g and 7h showed the most potent anti-AChE and anti-BuChE activities, respectively. Molecular docking and dynamic studies of the compounds 7g and 7h, respectively, in the active site of AChE and BuChE revealed that these compounds as well interacted with studied cholinesterases. These compounds also possessed drug-like properties and were able to cross the BBB.

A new series of 1,2,3-triazole-(thio)barbituric acid hybrids 8a-n was designed and synthesized on the basis of potent pharmacophores with urease inhibitory activity. Therefore, these compounds were evaluated against Helicobacter pylori urease. The obtained result demonstrated that all the synthesized compounds, 8a-n, were more potent than the standard urease inhibitor, hydroxyurea. Moreover, among them, compounds 8a, 8c-e, 8g,h, and 8k,l exhibited higher urease inhibitory activities than the other standard inhibitor used: thiourea. Docking studies were performed with the synthesized compounds. Furthermore, molecular dynamic simulation of the most potent compounds, 8e and 8l, showed that these compounds interacted with the conserved residues Cys592 and His593, which belong to the active site flap and are essential for enzymatic activity. These interactions have two consequences: (a) blocking the movement of a flap at the entrance of the active site channel and (b) stabilizing the closed active site flap conformation, which significantly reduces the catalytic activity of urease. Calculation of the physicochemical and topological properties of the synthesized compounds 8a-n predicted that all these compounds can be orally active. The ADME prediction of compounds 8a-n was also performed.

An efficient multi-component synthesis of highly functionalized 2,2′-bifurans and 2-(thiophen-2-yl)furans is described. A mixture of furan- or thiophene-2-carbonyl chloride, an isocyanide, and a dialkyl acetylenedicarboxylate undergoes a smooth addition reaction in dry CH2Cl2 at ambient temperature to produce 2-amino-5-(4-chlorofuran-2-yl)furan-3,4-dicarboxylates and 2-amino-5-(4-chlorothiophen-2-yl)furan-3,4-dicarboxylates. A single-crystal X-ray-analysis of a derivative conclusively confirms the structure of these 2,2′-bifurans and 2-(thiophen-2-yl)furans. A novel electrophilic aromatic substitution reaction can justify the formation of the Cl-substituted furan or thiophene rings.

A one-pot four-component synthesis of thieno[2,3-d]pyrimidin-4-amines via sequential Gewald/cyclocondensation reactions is described. 2-Aminothiophene-3-carbonitriles obtained from the Gewald reaction between cyclic ketones, malononitrile, and sulfur underwent a condensationcyclization reaction with benzonitriles under solvent-free conditions to afford the title compounds in excellent yields.

A one-pot four-component synthesis of thieno[2,3-d]pyrimidin-4-amines via sequential Gewald/cyclocondensation reactions is described. 2-Aminothiophene-3-carbonitriles obtained from the Gewald reaction between cyclic ketones, malononitrile, and sulfur underwent a condensationcyclization reaction with benzonitriles under solvent-free conditions to afford the title compounds in excellent yields.

A simple synthesis of N2-alkyl-N3-[2-(1,3,4-oxadiazol-2-yl)aryl]benzofuran-2,3-diamines 5via a one-pot four-component reaction is described (Scheme 1). A mixture of N-(isocyanoimino)triphenylphosphorane (1), a 2-aminobenzoic acid 2, a 2-hydroxybenzaldehyde 3, and an isocyanide 4 in absolute EtOH at room temperature undergoes a smooth reaction to afford 5 in excellent yields (Table).

A simple method for the preparation of alkyl 2-aminobenzo[b]thiophene-3-carboxylates is described. Alkyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylates, generated from the Gewald three-component reaction between cyclohexanones, alkyl cyanoacetates and sulfur, undergo dehydrogenation in benzonitrile under an air atmosphere to afford alkyl 2-aminobenzo[b]thiophene-3-carboxylates in good to excellent yields.

An open, randomized, controlled study with two parallel treatment groups was done to evaluate the efficacy of a miconazole 2% gel compared with Zataria multiflora 0.1% gel applied four times daily for 2 weeks, in the treatment of Candida-associated denture stomatitis. Twenty four patients were included in the study. The efficacy variables were the colony count of Candida from the palatal mucosa and the denture surface and the erythema surface of the palatal mucosa on days 0, 7, 14, 21 and 28 after commencement of therapy. Twelve patients received miconazole gel and twelve Z. multiflora gel. The erythema surface was significantly reduced by both gels. No significant difference was seen between the two groups (p < 0.05). There was a significant reduction in the colony count of the palatal mucosa in both groups (except on days 21 and 28 in the Zataria group p = 0.07 and 0.08). Miconazole treatment reduced the number of denture colonies more efficiently than Z. multiflora except for day 21 when the efficacy of both groups was similar (p = 0.17). The results indicate that Z. multiflora gel reduced the surface erythema of the palate more efficiently than miconazole gel but did not reduce the colony count of the denture surface as efficiently as miconazole.

Polyadipic anhydride (PAA), an aliphatic polyanhydride, and polytrimethylene carbonate (PTMC), an aliphatic polycarbonate, were synthesized via ring opening polymerization of oxepan-2,7-dione and melt-condensation of trimethylene carbonate (1,3 dioxan-2-one), respectively. PTMC–PAA blend microspheres containing different ratios of buprenorphine HCl (2, 5, and 10%) were prepared by an oil-in-oil emulsion solvent removal method. Microspheres with different ratios of PTMC–PAA (85/15, 70/30, and 55/45) containing 5% buprenorphine HCl were prepared. Microspheres were spherical with visible cracks and pores on the surface. The average particle size of microspheres was around 200 μm for all microspheres. Drug loading efficiency of PTMC–PAA microspheres (85/15, 70/30, and 55/45) was 97.2, 95.2, and 70.2%, respectively. With the increase in the PTMC ratio, the melting point and the enthalpy of melting were both decreased. The mechanism for drug release from PTMC–PAA blend microspheres were generally a combination of drug diffusion through polymers and biodegradation of the polymers. In first three days, the release from microspheres followed zero order kinetics and was dependent on the PAA content. After three days the drug release from microspheres followed first order kinetics. In conclusion it was demonstrated that buprenorphine HCl release from microspheres could be successfully controlled by using different ratios of PTMC–PAA blends. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2377–2383, 2006

Controlled drug-delivery technology is concerned with the systematic release of a pharmaceutical agent to maintain a therapeutic level of the drug in the body for modulated and/or prolonged periods of time. This may be achieved by incorporating the therapeutic agent into a degradable polymer vehicle, which releases the agent continuously as the matrix erodes. In this study, poly trimethylene carbonate (PTMC), an aliphatic polycarbonate, and poly adipic anhydride (PAA), an aliphatic polyanhydride, were synthesized via melt condensation and ring-opening polymerization of trimethylene carbonate and adipic acid, respectively. The release of clomipramine HCl and buprenorphine HCl from discs prepared with the use of PTMC-PAA blends in phosphate buffer (pH 7.4) are also described. Clomipramine HCl and buprenorphine HCl were both used as hydrophilic drug models. Theoretical treatment of the data with the Peppas model revealed that release of clomipramine HCl (5%) in devices containing 70% PTMC or more followed a Fickian diffusion model. However, the releases of buprenorphine HCl (5%) in the same devices were anomalous. For devices containing 50% and more PAA, surface erosion may play a significant role in the release of both molecules.

The essential oils of the wild and cultivated Satureja khuzistanica Jamzad (Lamiaceae) from Iran were isolated by hydrodistillation in yields of 0.6% and 1.2% respectively. The chemical composition of the essential oils was examined by GC and GC–MS. Twelve components of the wild plants' oil, representing 98.5% of the total oil, and 21 components of the cultivated plants' oil, representing 99.2%, were identified. The main components of the wild plants' oil were carvacrol (93.9%), eugenol (1.0%), p-cymene (0.8%) and thymol (0.6%). The major constituents of the cultivated plants' oil were carvacrol (80.6%), p-cymene (4.8%), myrcene (1.5%), γ-terpinene (2.1%) and terpinene-4-ol (2.1%). In both the wild and cultivated plants the main component of the oil was carvacrol. Copyright © 2004 John Wiley & Sons, Ltd.