ANTIMICROBIAL AND ANTI-INFLAMMATORY STUDIES ON SARGASSUM WIGHTII EXTRACTS

Objective: To evaluate the antimicrobial and anti-inflammatory effect of hexane, chloroform and ethanolic extract of Sargassum wightii. Methods: Hexane, chlorofom and ethanolic extractions of these algae were done and evaluated for biological activity. Assay of antimicrobial activity was perfomed by disc diffusion method against various microorganisms. Assay of anti-inflammatory activity was performed in albino rats with paw edema, induced by Carrageenan. Results: Chloroform and ethanol extracts exhibited antimicrobial activity against various microorganisms. All the extracts revealed anti-inflammatory activity, in which chloroform extract showed maximum activity in dose dependent manner. Conclusions: Among the three different extracts tested, chloroform extract of S. wightii possess significant antimicrobial and anti-inflammatory activities. Further in-depth studies, could result in the development of a good antimicrobial and anti-inflammatory agent from this chloroform extract of S.wightii

Controlling selectivity in photochemical reactions through confinement and non bonding interactions

Work presented in this thesis is the consolidation of our experiments aimed at achieving selectivity in photochemical reactions by making use of confinement provided by the host and the weak intermolecular interactions existing between the host and the guest(s) molecules. Two supramolecules namely Pd-nanocage (a water soluble self assembled coordination cage) and commercially available Y zeolites were used as hosts to conduct photochemical reactions. The cavities provided by these host molecules were used as a reaction vessel to conduct photochemical reactions.Chapter 1 gives a brief overview of supramolecular organic chemistry. The supramolecules reported in the literature which are related to the work presented in this thesis are discussed. Research conducted by using these supramolecules with the aim of achieving selectivity in photochemical reactions is also discussed.Chapter 2 presents the utility of hydrophobic cavity provided by water soluble octahedral Pd-nanocage to conduct photodimerization reaction of coumarins. With the help of five different coumarin molecules we have shown that syn head-head dimer is formed as the major product when the reaction is conducted within Pd-nanocage. The weak intermolecular forces existing between the host and the guest(s) (C-H---pi, pi---pi) and the compactness of the dimer are held responsible for such behaviour.Chapter 3 presents the utility of hydrophobic cavity provided by Pd-nanocage in conducting photodimerization of trans-cinnamic acid esters. This work is an extension of the work presented in Chapter 2. Unlike coumarins, trans-cinnamic acid esters have two reaction pathways namely isomerization and dimerization. Isomerization is the major pathway during solution phase irradiation of trans-cinnamic acid esters. Irradiation of the host-guest complexes of trans-cinnamic acid methyl esters with the Pd-nanocage resulted in the selective formation of syn head-head dimer in addition to the corresponding cis isomer. The obtained results suggest that the guest molecules are preoriented in a selective fashion within the Pd-nanocage. Weak intermolecular forces between the host and the guest(s) (C-H---pi, pi---pi) are likely to be responsible for the lack of mobility of the reactant olefins during their short excited state life time.Chapter 4 deals with photodimerization of anthracene derivatives and triplet sensitized photodimerization of acenaphthalene within Pd-nanocage. Among the anthracene derivatives studied, only 9-anthraldehyde (4b) dimerized within Pd-nanocage yielding head-tail dimer. The other anthracene derivatives inspite of long wavelength absorption were photoinactive within Pd-nanocage. In the case of triplet sensitized photodimerization of acenapthalene, water soluble xanthene dyes were used as sensitizers. The triplet sensitized photodimerization of acenapthalene within Pd-nanocage yielded the syn dimer exclusively.Chapter 5 discusses the results obtained during stereoselective photocyclization of pyridones within zeolites. Two approaches namely chiral inductor approach and chiral auxiliary approach were employed with the aim of achieving stereoselectivity during photocyclization of pyridones. Enantioselectivity of around 55% and diastereoselectivity of around 88% were obtained. The charge compensating cations of the zeolites, their interaction with the guest molecules and the confinement provided by the zeolite interior are held responsible for the observed stereoselectivity.Chapter 6 deals with probing the cation organic interaction existing between organic molecules and the charge compensating cations of the zeolites by solid state NMR experiments. Static, magic angle spinning and cross-polarization magic angle spinning experiments were employed to study the cation-organic interaction. These experiments suggested the existence of an interaction between the organic molecules and the charge compensating cations of the zeolites

Value of zeolites in asymmetric induction during photocyclization of pyridones, cyclohexadienones and naphthalenones

Two strategies, namely chiral inductor and chiral auxiliary approaches, have been examined within zeolites with the aim of achieving asymmetric induction during the photocyclization of cyclohexadienone, naphthalenone and pyridone derivatives. Within zeolites, enantioselectivity as high as 55% and diastereoselectivity as high as 88% have been obtained. The observed stereoselectivities are significant given the fact that these reactions gave very little stereoselectivities in isotropic solution media. The results obtained on the photocyclization of dienones, naphthalenones and N-alkyl pyridones within zeolites compliment our earlier investigations on the photocyclization of tropolone derivatives, the geometric isomerization of 1,2-diphenylcyclopropanes and 2,3-diphenyl-1-benzoyl cyclopropanes, and the Norrish type II reaction of a-oxoamides, phenyl adamantyl ketones, phenyl norbornyl ketones and phenyl cyclohexyl ketones. With the help of these examples, we have established the importance of zeolite and its charge compensating cations in effecting asymmetric induction in photochemical reactions

Asymmetric induction during electron transfer mediated photoreduction of carbonyl compounds: role of zeolites

Photochemistry of 17 aryl alkyl ketones included within cation exchanged zeolites has been examined. In solution five of the 17 ketones undergo intramolecular hydrogen abstraction reaction even in the presence of a chiral amine and the rest are photoreduced to the corresponding alcohol. Within zeolites all 17 ketones yielded in presence of a chiral amine, the corresponding alcohol as the major product. When a chiral amine was used as the coadsorbent within alkali ion exchanged zeolites, enantiomerically enriched alcohol was formed in all cases. The best chiral induction was obtained with phenyl cyclohexyl ketone (enantiomeric excess: 68%). 1H-13C Cross Polarization Magic Angle Spinning (CP-MAS) experiments, with a model ketone (perdeuterated acetophenone) and chiral amine (pseudoephedrine) included within MY zeolites, suggested that the cation brings the reactant and the chiral amine closer. The role of the cation in such a process is also revealed by the computation results. The results presented here highlight the importance of a supramolecular structure in forcing a closer interaction between a reactant and a chiral inductor that could be used to achieve asymmetric induction in photoproducts

Antistreptokinase antibodies and outcome of fibrinolytic therapy with streptokinase for left-sided prosthetic valve thrombosis

Background: Left-sided prosthetic valve thrombosis (PVT) is a serious complication of valve replacement. In developing countries, fibrinolysis with streptokinase (SK) is often used as the first line of treatment. Anti-streptokinase (anti-SK) antibodies are widely prevalent in the general population, but their effect on the efficacy and outcome of fibrinolysis with SK in patients with PVT is not known. Methods: Patients with rheumatic heart disease and prosthetic valve replacement presenting with a first episode of left-sided PVT were enrolled. All patients underwent fibrinolysis with SK. An indirect enzyme-linked immunosorbent assay was used to detect anti-SK antibodies before fibrinolysis. Relationship of these antibodies to the outcome of fibrinolysis was evaluated. Results: Forty-four patients treated for left-sided PVT were included. Thrombosis affected 33 mitral and 11 aortic prosthetic valves. On fibrinolysis with SK, 32 (73%) patients achieved complete success, whereas it was unsuccessful in the remaining 12 patients. There were 3 bleeding events, 1 stroke, and 3 deaths. Mean anti-SK antibody levels were not significantly different between patients who had complete success and those who did not (8.81 ± 2.43 vs 7.67 ± 1.26 Au/mL; P = .13) and did not correlate with the outcome after adjustment with other variables. Patients in New York Heart Association class III or IV had a greater chance of failed fibrinolytic therapy, even after adjustment for other prognostic variables (odds ratio 9.0; 95% CI 1.29-63.02; P = .027). Conclusion: Anti-SK antibody titers are not associated with success of fibrinolytic therapy using SK in patients with left-sided PVT

Inflammatory markers are elevated in Eisenmenger syndrome

Inflammation may be an important contributing factor to the progression of Eisenmenger syndrome (ES). Markers of systemic inflammation in ES have not been systematically studied. Inflammatory markers including high-sensitivity C-reactive protein (hs-CRP), interleukin-2 (IL-2), IL-6, and interferon-γ (IFN-γ) were measured in 42 consecutive ES patients (mean age, 24.3 ± 10.6 years) compared with their levels in 22 healthy control subjects. The patients were followed up for a mean duration of 16.3 ± 13.7 months. The levels of inflammatory markers were correlated with clinical and hemodynamic variables at baseline and the outcomes of death, hospitalization, and worsening World Health Organization (WHO) functional class at follow-up evaluation. Compared with the control subjects, ES patients showed a significant elevation in hs-CRP (2.99 ± 3.5 vs 1.1 ± 0.9 mg/dl; p = 0.002) and IFN-γ (41.3 ± 43.6 vs 10.4 ± 6.9 pg/ml; p < 0.001) levels. The levels of IL-2 and IL-6 also were elevated but did not differ significantly from those in the control subjects. The patients with hs-CRP levels higher than 3 mg/dl were significantly older (28.9 ± 10.6 vs 21.5 ± 9.8 years) and had a significantly shorter 6-min walk distance (421.5 ± 133.2 vs 493.3 ± 74.8 m). The levels of inflammatory markers did not correlate with baseline parameters or clinical outcomes. To conclude, the levels of hs-CRP and IFN-γ are significantly elevated in ES. Elevated hs-CRP in ES was associated with older age and shorter 6-min walk distance, but the levels of inflammatory markers were not predictive of clinical events