Bioactive aristolactams from Piper umbellatum

Four alkaloids named piperumbellactams A-D (1-4) were isolated from branches of Piper umbellatum together with known N-hydroxyaristolam II (5), N-p-coumaroyl tyramine (6), 4-nerolidylcatechol (7), N-trans-feruloyltyramine, E-3-(3,4-dihydroxyphenyl)-N-2-[4-hydroxyphenylethyl]-2-propenamide, beta-amyrin, friedelin, apigenin 8-C-neohesperidoside, acacetin 6-C-beta-d-glucopyranoside, beta-sitosterol, its 3-O-beta-d-glucopyranoside and its 3-O-beta-d-[6'-dodecanoyl]-glucopyranoside. Glycosidase inhibition, antioxidant and antifungal activities of these compounds were evaluated. Compounds 1-3 showed moderate alpha-glucosidase enzyme inhibition with IC50 values 98.07+/-0.44, 43.80+/-0.56 and 29.64+/-0.46, respectively. In DPPH radical scavenging assay, compounds 2, 3 and 6 showed potent inhibitory activity while compounds 4, 5 and 7 showed potent antifungal activity.     

Exploration of <Emphasis Type="Italic">Csp</Emphasis> Genes from Temperate and Glacier Soils of the Indian Himalayas and <Emphasis Type="Italic">In Silico</Emphasis> Analysis of Encoding Proteins

The metagenomic Csp library was constructed from the temperate and glacier soils of central Himalaya, India followed by polymerase chain reaction (PCR) amplification. The library was further screened for low-temperature adaptation, and the positive recombinants were sorted out by determining changes in the melting temperature (Tm). A homology search of cloned sequence showed their identity with the Csp genes of Pseudomonas fluorescens, Psychrobacter cryohalolentis K5, and Shewanella spp MR-4. Amino acid sequence analysis annotated the presence of conserved aromatic and basic amino acids as well as RNA binding motifs from the cold shock domain. Furthermore, a PROSITE scan showed a moderate identity of less than 60% with the known cold shock-inducible proteins (ribosomal proteins, rbfA, DEAD-box helicases), cold acclimation protein, and temperature-induced protein (SRP1/TIP1). This study highlighted the prevalence of Csp genes from cold Himalayan environments that can be explored for tailor-made crop constructions in future.     

Cardioprotection by HO-4038, a novel verapamil derivative, targeted against ischemia and reperfusion-mediated acute myocardial infarction

Many cardiac interventional procedures, such as coronary angioplasty, stenting, and thrombolysis, attempt to reintroduce blood flow (reperfusion) to an ischemic region of myocardium. However, the reperfusion is accompanied by a complex cascade of cellular and molecular events resulting in oxidative damage, termed myocardial ischemia-reperfusion (I/R) injury. In this study, we evaluated the ability of HO-4038, an N-hydroxypiperidine derivative of verapamil, on the modulation of myocardial tissue oxygenation (Po(2)), I/R injury, and key signaling molecules involved in cardioprotection in an in vivo rat model of acute myocardial infarction (MI). MI was created in rats by ligating the left anterior descending coronary artery (LAD) for 30 min followed by 24 h of reperfusion. Verapamil or HO-4038 was infused through the jugular vein 10 min before the induction of ischemia. Myocardial Po(2) and the free-radical scavenging ability of HO-4038 were measured using electron paramagnetic resonance spectroscopy. HO-4038 showed a significantly better scavenging ability of reactive oxygen radicals compared with verapamil. The cardiac contractile functions in the I/R hearts were significantly higher recovery in HO-4038 compared with the verapamil group. A significant decrease in the plasma levels of creatine kinase and lactate dehydrogenase was observed in the HO-4038 group compared with the verapamil or untreated I/R groups. The left ventricular infarct size was significantly less in the HO-4038 (23 +/- 2%) compared with the untreated I/R (36 +/- 4%) group. HO-4038 significantly attenuated the hyperoxygenation (36 +/- 1 mmHg) during reperfusion compared with the untreated I/R group (44 +/- 2 mmHg). The HO-4038-treated group also markedly attenuated superoxide production, increased nitric oxide generation, and enhanced Akt and Bcl-2 levels in the reperfused myocardium. Overall, the results demonstrated that HO-4038 significantly protected hearts against I/R-induced cardiac dysfunction and damage through the combined beneficial actions of calcium-channel blocking, antioxidant, and prosurvival signaling activities.     

Synthesis of 6-deoxy-6-chloro and 6-deoxy-6-bromo derivatives of scleroglucan as intermediates for conjugation with methotrexate and other carboxylate containing compounds

Polysaccharides are widely used as carriers in the field of drug delivery. We present a methodology to obtain water soluble drug-conjugates based on scleroglucan. Selective C-6 halogenation gives access to C-6 esters; conjugates between methotrexate and scleroglucan are described, potentially useful for antitumour therapy or in rheumatoid arthritis treatment.     

Characterization of bacterial endophytes of sweet potato plants

Endophytic bacteria associated with sweet potato plants (Ipomoea batatas (L.) Lam.) were isolated, identified and tested for their ability to fix nitrogen, produce indole acetic acid (IAA), and exhibit stress tolerance. Eleven different strains belonging to the genera, Enterobacter, Rahnella, Rhodanobacter, Pseudomonas, Stenotrophomonas, Xanthomonas and Phyllobacterium, were identified. Four strains were shown to produce IAA (a plant growth hormone) and one strain showed the ability to grow in nitrogen free medium and had the nitrogenase subunit gene, nifH. To determine if IAA production by the endophytes had any role in protecting the cells against adverse conditions, different stress tests were conducted. The IAA producer grew well in the presence of some antibiotics, UV and cold treatments but the response to pH, osmotic shock, thermal and oxidative treatments was the same for both the IAA producer and the no IAA producer. To determine if IAA produced by the strains was biologically relevant to plants, cuttings of poplar were inoculated with the highest IAA producing strain. The inoculated cuttings produced roots sooner and grew more rapidly than uninoculated cuttings. These studies indicate that endophytes of sweet potato plants are beneficial to plant growth.     

Pregnane glycosides from Hoodia gordonii

Hoodia gordonii is a ‘weight loss’ herb, which has gained popularity in the western countries as an appetite suppressant dietary supplement. Phytochemical study of its aerial parts led to isolation of seven pregnane glycosides (hoodigosides W-Z, hoodistanalosides A-B). Their structures were elucidated by chemical degradation studies and spectroscopic methods, including 1D and 2D NMR and CD spectroscopic methods.     

Genetic Characterization of a New Growth Habit Mutant in Tomato (<Emphasis Type="Italic">Solanum lycopersicum</Emphasis>)

A mutant tomato cultivar (HT10-3-2) with indeterminate growth habit was obtained from a cultivar (T10-3-2) with determinate growth habit. The character of indeterminate growth habit in HT10-3-2 could be inherited stably. Unlike other normal growth habit cultivars, which are controlled by the SELF PRUNING gene, it was shown here that HT10-3-2 has no mutation in the sp gene. Two hundred random amplified polymorphic DNA (RAPD) primers were used to screen for polymorphism between the two genotypes from genomic DNA, and a polymorphic fragment (S168₁₄₅₈) was obtained and subsequently sequenced. However, Basic Local Alignment Search Tool searches indicated that the sequence of this RAPD fragment shares no significant homology with known sequences in GenBank. The RAPD marker (S168₁₄₅₈) was converted to a sequence characterized amplified region (SCAR) marker, SCA168₁₄₅₃. The SCAR marker was tested using an F₂ population derived from the cross of T10-3-2 and HT10-3-2 and the results showed that this marker was closely linked with the unknown factor influencing the growth habit in HT10-3-2.     

Enantiomer self-disproportionation of chiral compounds on achiral ordered mesoporous silica M41S and regular silica gel as a stationary phase

Chromatographic behavior of nonracemic mixtures, viz., mandelic acid and stilbene oxide as analytes has been studied in detailed by enantiomer self-disproportionation on achiral ordered mesoporous material M41S and regular silica gel as stationary phases. Enantiomer self-disproportionation gave enhanced separation of analytes. The extent and magnitude of enantiomer self-disproportionation is dependent on the optical purity of the starting non-racemic molecules, presence of intermolecular hydrogen bonding/pi-pi interactions and the nature of eluents used. The present study and previous literature data suggest that percentage ee of a nonracemic mixture needs to be determined before any chromatographic purification is taken up as enantiomer self-disproportionation phenomenon could occur during purification. The data show that enantiomer self-disproportionation of nonracemic mixtures can be harnessed for its enantioenrichment on inexpensive achiral stationary phases.     

Serum sialic acid changes in non-insulin-dependant diabetes mellitus (NIDDM) patients following bitter melon (Momordica charantia) and rosiglitazone (Avandia) treatment

Diabetes mellitus is associated with an increase in sialic acid concentration along with other complications. Sialic acid changes in NIDDM patients were investigated following bitter melon (55 ml/24 h) and rosiglitazone (4 mg/24 h) treatment. A total of 25 patients of both sexes were used in each experimental group. Patients following bitter melon treatment showed no significant difference of serum sialic acid (57.95±4.90 vs. 57.6±5.56 mg/dl, p=0.17) and serum glucose concentration (93.7±9.63 vs. 88.35±6.31 mg/dl, p=0.78) as compared to control subjects. However, the concentration of total cholesterol was significantly high in these patients as compared to control subjects (192±14.23 vs. 170.6±15.1 mg/dl, p<0.03) but within normal range (160–200 mg/dl), suggesting the significant hypoglycemic and lipid-lowering properties of bitter melon. The patients following rosiglitazone treatment showed a significant increase of serum sialic acid concentration (60.2±5.80 vs. 57.6±5.56 mg/dl, p=0.01) along with glucose (112±6.2 vs. 88.35±6.31 mg/dl, p<0.04) and total cholesterol concentration (216.45±20.2 vs. 170.6±15.1 mg/dl, p<0.01) as compared to control subjects. In addition six of the patients had retinopathy, two of whom were suffering also from myocardial infarction and they still had a higher serum sialic acid (61.05±1.20 mg/dl), glucose (187±2.11 mg/dl), total cholesterol (239.10±5.04 mg/dl) and triglyceride (183±4.14 mg/dl) concentration, indicating a poor response of these patients to rosiglitazone. Comparison of serum sialic acid concentration of patients, following bitter melon and rosiglitazone treatment revealed no significant difference but the study showed that bitter melon could be more effective in the management of diabetes and its related complications as compared to rosiglitazone.