Yes / Magnolia champaca Linn. has traditionally been used for medicinal activity in Asia for treating various chronic diseases as well as a source of food, medicines, and other commodities. Due to the long-used history of this plant, the present study was designed to explore the in vitro, in vivo and in silico anti-inflammatory and antineoplastic properties of the methanolic extract and fractions and the pure compound isolated from the most active chloroform fraction (CHF) of the stem bark of the plant. The isolated compound from the most active CHF was characterized and identified as a glycoside, trans-syringin, through chromatographic and spectroscopic (1H-NMR and 13C-NMR) analyses. In the in vitro anti-inflammatory assay, CHF was most effective in inhibiting inflammation and hemolysis of RBCs by 73.91 ± 1.70% and 75.92 ± 0.14%, respectively, induced by heat and hypotonicity compared to standard acetylsalicylic acid. In the egg albumin denaturation assay, CME and CHF showed the highest inhibition by 56.25 ± 0.82% and 65.82 ± 3.52%, respectively, contrasted with acetylsalicylic acid by 80.14 ± 2.44%. In an in vivo anti-inflammatory assay, statistically significant (p < 0.05) decreases in the parameters of inflammation, such as paw edema, leukocyte migration and vascular permeability, were recorded in a dose-dependent manner in the treated groups. In the antineoplastic assay, 45.26 ± 2.24% and 68.31 ± 3.26% inhibition of tumor cell growth for pure compound were observed compared to 73.26 ± 3.41% for standard vincristine. Apoptotic morphologic alterations, such as membrane and nuclear condensation and fragmentation, were also found in EAC cells after treatment with the isolated bioactive pure compound. Such treatment also reversed the increased WBC count and decreased RBC count to normal values compared to the untreated EAC cell-bearing mice and the standard vincristine-treated mice. Subsequently, in silico molecular docking studies substantiated the current findings, and the isolated pure compound and standard vincristine exhibited −6.4 kcal/mol and −7.3 kcal/mol binding affinities with topoisomerase-II. Additionally, isolated pure compound and standard diclofenac showed −8.2 kcal/mol and −7.6 kcal/mol binding affinities with the COX-2 enzyme, respectively. The analysis of this research suggests that the isolated bioactive pure compound possesses moderate to potent anti-inflammatory and antineoplastic activity and justifies the traditional uses of the stem bark of M. champaca. However, further investigations are necessary to analyze its bioactivity, proper mechanism of action and clinical trials for the revelation of new drug formulations.

Homopolymers and copolymers produced from aromatic based methacrylates, acrylates, and dimethacrylates are excellent materials with many applications in dentistry, microelectronics, and optics, including optical eye wear, fiber optics, and non-linear optics, such as holography. Carbazole based polymers have demonstrated good optical, photo-refractive, and charge-transporting properties, combined with ease of processing. The objective of this research was to design, synthesize, and characterize high refractive index polymers and copolymers for use in optical spectacle lenses of eyeglasses. Additionally, other interesting attributes were observed for selected carbazole based polymers, such as high thermal stability and birefringence, which could lend these materials to other uses, such as non-linear optics and electronic data storage. A family of novel, high refractive index homopolymers and copolymers were synthesized by incorporating carbazole, along with other aromatic substituents, into methacrylates, acrylates, and dimethacrylates. Subsequent free radical polymerizations provided for high refractive index materials well suited for lightweight optical spectacles and other applications. The refractive index of materials can be increased by increasing the polarizability of substituent groups. By incorporating oxygen, sulfur, or sulfoxide groups into polymers, high refractive index polymers have been attained. By reacting the phenol, aromatic diols, or aromatic thiols with 9-(2,3-epoxypropyl)-carbazole, the refractive index of the final polymer can be increased further. The reaction of the carbazole based intermediate with methacryloyl chloride or methacrylic anhydride eliminated any hydroxyl groups in the final methacrylate or dimethacrylate. Hydroxyl groups undergo intermolecular hydrogen bonding, which increases viscosity. The absence of hydrogen bonding in the final methacrylated monomers reduces viscosity, which is desirable for processing. Novel carbazole based monomers and polymers were characterized in terms of molecular composition and molecular weight, thermal properties, such as melting point, glass transition temperature, and decomposition, and in terms of optical properties, such as refractive index. The AIBN initiated carbazole-phenoxy based methacrylate polymerization was followed using in-situ FTIR, which showed the reaction to be completed within 40 minutes in DMAC at 90°C. Photo-DSC was used to determine the heat of polymerization (DHp) for the carbazole-phenoxy based methacrylate, which was found to be -39.4 kJ/mole. One and two dimensional 1H NMR was used to characterize the molecular structure of the carbazole-phenoxy based methacrylate monomer. The carbazole-phenoxy based methacrylate homopolymer had a surprisingly high decomposition temperature. 13C NMR spectroscopy experiments and molecular modeling were employed to explore the configuration of the polymerized carbazole-phenoxy based methacrylate. The lack of head-to-head linkages due to steric considerations could explain the higher thermal stability observed for the carbazole-phenoxy based methacrylate polymer. Refractive indices of these carbazole based methacrylates, acrylates, and dimethacrylate polymers ranged from 1.53 to 1.63. Statistical copolymers of carbazole based methacrylates with methyl methacrylate were also produced by solution polymerization in DMAC, and characterized. Using free radical polymerization techniques, homopolymers and copolymers of the carbazole functionalized methacrylates, acrylates, and dimethacrylates were readily obtained. This research demonstrated a variety of carbazole based chemistries which could produce controlled linear and cross-linked materials with high refractive index values and other interesting features. / Ph. D.

Abstract The processes affecting myocardial survival in ischemia were studied in perfused rat hearts by using largely non-invasive methods based on optical monitoring and nuclear magnetic resonance (NMR). Ischemic preconditioning (IPC) has been shown to protect the heart considerably from ischemic damage in all species studied. F1Fo-ATPase inhibition has been suggested to involve the mechanism of IPC, but its significance has been doubted, partly because ischemic inhibition of F1Fo-ATPase has been considered insignificant in rat. An improved method of F1Fo-ATPase activity measurement was used in which the time-consuming isolation of mitochondria was omitted and the salt concentration and pH conditions were optimized. It was demonstrated that ischemic F1Fo-ATPase inhibition does occur in rat, and that the method can also be applied in human myocardium. The mitochondrial ATP-sensitive potassium (mitKATP) channel opener, diazoxide, attenuated myocardial damage and enhanced ischemic inhibition of F1Fo-ATPase similar to IPC. All of these effects were abolished with the mitKATP inhibitor 5-HD. These results suggest that mitKATP opening is connected to F1Fo-ATPase inhibition in the mechanism of IPC. Observations of the nature of F1Fo-ATPase inhibition in isolated mitochondria suggest that IF1 binding is involved in the inhibition. Calcium perturbations in ischemia-reperfusion were studied in intact heart using calcium probing with Fura-2. It was found that compensation for tissue autofluorescence and pH changes were necessary for reliable Ca2+ monitoring. IPC significantly decreased myocardial calcium accumulation in ischemia, and magnesium quenching of cytosolic Fura-2 fluorescence showed that this is mainly mitochondrial. The attenuation of mitochondrial calcium overload was connected to an enhanced decrease in mitochondrial membrane potential in IPC. The role of calcium in respiratory control and in substrate selection was studied during fatty acid oxidation. The energy state evaluated by 31P-NMR decreased slightly during hexanoate infusion upon calcium-induced inotrophy, and a tendency for NADH and flavoprotein oxidation was also monitored. These observations are in agreement with the theory that mitochondrial respiration is mainly determined by the energy expenditure. Even a 50 μM octanoate concentration completely surpassed glucose and internal substrates as a preferential myocardial energy source. The fatty acid dominance remained unaltered even upon a calcium-induced increase in energy consumption evaluated by 13C-NMR. The rate of anaplerosis was found to be considerable during octanoate oxidation, and it was emphasised during low cardiac workload.