Muhammad Raza Shah

Synthetic ion channels and pores (2004–2005)

This critical review covers synthetic ion channels and pores created between January 2004 and December 2005 comprehensively. The discussion of a rich collection of structural motifs may particularly appeal to organic, biological, supramolecular and polymer chemists. Functions addressed include ion selectivity and molecular recognition, as well as responsiveness to light, heat, voltage and membrane composition. The practical applications involved concern certain topics in medicinal chemistry (antibiotics, drug delivery), catalysis and sensing. An introduction to principles and methods is provided for the non-specialist; some new sources of inspiration from fields beyond chemistry are highlighted.

Enantioselective chromatography—A powerful tool for the discrimination of biotic and abiotic transformation processes of chiral environmental pollutants

On the basis of the general principles of chirality the characteristics of chromatograms obtained by enantioselective GC and HPLC are explained, followed by a description of different enantioselective chromatographic methods (HPLC, high-resolution GC, multidimensional GC, CE, supercritical fluid chromatography) thus far applied. The potential of enantioselective chromatography is highlighted by examples of studies on microbial, enzymatic and photochemical transformation processes, on air/sea exchange and long-range transport processes, enantioselective toxic effects as well as on the fate of emerging environmental chiral pollutants such as pharmaceuticals, personal care products and the flame retardant 1,2,5,6,9,10-hexabromocyclododecane.

Urease inhibitors from Hypericum oblongifolium WALL.

The bioassay-guided fractionation of H. oblongifolium has led to the isolation of potent urease inhibitors 1–3. The structures were elucidated by NMR and mass spectroscopic techniques. Compound 2 showed a potent enzyme inhibition activity (IC50 20.96 ± 0.93), which is comparatively higher than that for the standard thiourea (IC50 21.01 ± 0.51 μM). Compounds 1 and 3 also showed a significant activity, with IC50 37.95 ± 1.93 and 138.43 ± 1.23 μM, respectively. The sub crude fractions (F1, F2, F3, and F4) were tested in vitro for their urease inhibition activity. Fractions F2 and F4 showed significant activity with IC50 140.37 ± 1.93 and 167.43 ± 3.03 μM, respectively.

Complete degradation of dimethyl phthalate by biochemical cooperation of the Bacillus thuringiensis strain isolated from cotton field soil

Dimethyl phthalate (DMP), a phthalate ester, is widely used in cosmetics, perfumes, and plasticizers. It has been classified as a suspected endocrine disruptor by many countries. The present study describes the biodegradation of DMP by a new aerobic bacterium, isolated from soil samples of a cotton field by an enrichment culture technique utilizing DMP as the sole source of carbon and energy. The isolate was identified as Bacillus thuringiensis based on the morphological and biochemical characteristics as well as gene sequence analysis. Bacillus thuringiensis grows best in a mineral salt medium of pH 7.0 at 30 °C incubation for 48 hours. The effects of temperature, inoculum size, substrate concentration and incubation time on DMP degradation were also studied. Bacillus thuringiensis is able to biodegrade 400 mg L−1 of DMP under aerobic conditions with 99% degradation potential. A combination of GC and GC-MS analysis revealed a complete DMP biodegradation pathway. The results indicate that Bacillus thuringiensis may prove a promising source for DMP bioremediation at a commercial scale.

Formation of tethered bilayer lipid membranes probed by various surface sensitive techniques

Tethered bilayer lipid membranes are promising biomimetic architectures. Their formation has been investigated using four different surface sensitive techniques, including optical, acoustic, and electrical methods. The lipid bilayers are built in a two-step procedure; the proximal layer is formed by self-assembly and is then completed to a bilayer by fusion with small vesicles. The different technical approaches revealed specific aspects of the layer formation processes, namely, first a fast adsorption process followed by a longer rearrangement period. Similar phenomena have been observed for the vesicle fusion process. The results allow for a more controlled assembly protocol for the preparation of highly insulating lipid membranes.

Identification and enantioselective gas chromatographic mass-spectrometric separation of O-desmethylnaproxen, the main metabolite of the drug naproxen, as a new environmental contaminant

O-desmethylnaproxen (2-(6-hydroxynaphthalen-2-yl)propanoic acid) was identified in 10 different water samples from Germany and Pakistan. In the Pakistan samples it was found in all samples, surface water and effluents, exhibiting estimated concentrations between 0.04 and 1.36 microg/L. In Germany it was only encountered in the STP-effluent with an average concentration of 0.23 microg/L. Furthermore, enantioselective GC analyses revealed differences in the enantiomeric ratios found in Germany and Pakistan. To the best of our knowledge this is the first report on the identification of O-desmethylnaproxen, the main metabolite of the drug naproxen, in environmental samples.

Anti-inflammatory activities of Taxusabietane A isolated from Taxus wallichiana Zucc.

Current study was conducted to identify constituents of Taxus wallichiana Zucc. that might be responsible for its folk use in anti-inflammatory conditions. Taxusabietane A was isolated from the bark extract of Taxus wallichiana Zucc. Taxusabietane A was analyzed for in-vitro and in-vivo anti-inflammatory activities using Lipoxygenase (LOX) inhibition assay and carrageenan-induced paw edema model. Taxusabietane A revealed considerable LOX inhibitory activity with the IC(50) value being 57 ± 0.31. Standard compound Baicalein showed the IC(50) value being 22.1 ± 0.03 μM. Taxusabietane A also showed significant (5 and 10 mg/kg) anti-inflammatory activity induced by carrageenan. However, this study highlighted the potential of Taxusabietane A to be further explored as a new lead compound for management of conditions associated with inflammation.

Chapter 5 – Recent Advances in the Dimroth Rearrangement: A Valuable Tool for the Synthesis of Heterocycles

Publisher Summary The Dimroth rearrangement (DR) is a translocation of two heteroatoms in a heterocyclic system, with or without changing its ring structure. The conversion of a heterocycle to a rearranged isomeric product can give one or two isomers via anintermediate, which selectively or specifically forms one of them as the major one. The stability of the rearranged product is the driving force for its formation, which may lead to the preference of one isomer. The heteroatoms which exchange positions in the rearrangement are S, N, O, and Se. DR can be divided into two types based on the positions of the translocating heteroatom(s): either both in the ring or one in the ring and the other located in an exocyclic position of that ring. This chapter discusses the translocation of heteroatoms between rings in fused heterocycles, and the translocation of exo-and endo-heteroatoms within a heterocyclic ring. In the process of rearrangement by translocation of heteroatoms between rings in fused heterocycles, the translocated heteroatoms are part of the ring. The translocation process changes the position of the heteroatom or the substituent on that ring leading to either a retained or a changed ring structure. The presence of a heteroatom within a five-membered ring and also at an exocyclic position of the adjacent ring is a promoting factor for the rearrangement. In the translocation of exo-and endocyclic heteroatoms in heterocyclic rings the translocation of heteroatom X (endocyclic in the ring) and Y (exocyclic to the ring) takes place during the rearrangement. All the processes are driven by the stability of the product, solvent, aromaticity of the ring, heteroatom valence, and bulkiness of the substituent.

Biologically Active C-Alkylated Flavonoids from Dodonaea viscosa

A new C-alkylated flavonoid (5,7-dihydroxy-3′-(4″-acetoxy-3″-methylbutyl)-3,6,4′-trimethoxyflavone (1), along with two known C-alkylated flavonoids (5,7-dihydroxy-3′-(3-hydroxymethylbutyl)-3,6,4′-trimethoxyflavone (2), 5,7,4′-trihydroxy-3′-(3-hyroxymethylbutyl)-3,6-dimethoxyflavone (3) and two new source C-alkylated flavonoids (5,7-dihydroxy-3′-(2-hydroxy-3-methyl-3-butenyl)-3,6,4′-trimethoxyflavone (4), 5,7,4′-trihydroxy-3,6-dimethoxy-3′-isoprenyl-flavone (5) were isolated from the aerial parts of Dodonaea viscosa. The structures of all compounds were established on the basis of 1D and 2D NMR spectroscopy and mass spectrometry. The isolated compounds were evaluated for their inhibitory effect on urease and α-chymotrypsin enzyme. All the compounds (1–5) exhibited mild inhibition against urease but remained recessive in case of α-chymotrypsin.

Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-α

Bergenin is an isocoumarin natural product which aides in fat loss, healthy weight maintenance, enhancing the lipolytic effects of norepinephrine, inhibiting the formation of interleukin 1α and cyclooxygenases-2. Here we describe the anti-inflammatory activity of new bergenin derivatives 1-15 in the respiratory burst assay. Bergenin was isolated from the crude extract of Mallotus philippenensis after repeated column chromatography and was then subjected to chemical derivatization. The structures of all compounds were elucidated by NMR and mass spectroscopic techniques. Compound 2 was also studied using single crystal X-ray diffraction. Compounds 4, (54.5±2.2%) 5 (47.5±0.5%) 5, and 15 (86.8±1.9%) showed significant (P≤0.005) NO inhibitory activities whereas 6, 7, 11, 12 and 13 displayed moderate inhibitory activities that ranges between 16% and 31%. Furthermore compounds 4 and 15, were discovered as significant (P≤0.005) TNF-α inhibitors with 98% and 96% inhibition, respectively, while compounds 3, 5, 7, 8, 11, and 12 showed low level of TNF-α inhibition (0.4-28%). Compounds 8, 13 and 15 exhibited moderate anti-inflammatory IC(50) activities with 212, 222, and 253 μM, respectively, compared to the standard anti-inflammatory drug indomethacin as well as the parent bergenin compound. No cytotoxic effects could be detected when the compounds were tested on 3T3 cells up to concentrations of 100 μM.