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In vivo, ex vivo, and in vitro proton magnetic resonance spectroscopy was performed in 12 patients with intracranial tuberculomas with an aim of detecting the biochemical constituents of Mycobacterium tuberculosis in a granuloma. One dimensional (1D) single pulse and spin-echo sequences and 2D correlative spectroscopy were used for the ex vivo study to confirm the resonances seen on in vivo study. Spectroscopic studies of the perchloric acid and lipid extract of granuloma and M. tuberculosis were performed to look for similarity of resonance. In vivo study showed the presence of lipids at 0.9, 1.3, 2.0, 2.8 ppm, and phosphoserine at 3.7 ppm. All these resonances were confirmed on ex vivo study. In addition, distinct resonances of serine and phenolic lipids were seen on ex vivo and in vitro study of tuberculous granuloma, which have not been observed in other intracranial tumors. Lipid extract of granuloma and M. tuberculosis showed phenolic lipids at 7.1 and 7.4 ppm, a constituent of the cell wall of the bacteria in a tuberculoma. It appears that it may be possible to finger print the biochemicals of the cell wall of M. tuberculosis in a tuberculous granuloma and thus may help in detection and diagnosis of such lesions.

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Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines), identified in our laboratory as potential pharmacophores for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for the high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxylate derivatives (3-7). The macrofilaricidal activity was initially evaluated in vivo against Acanthoeilonema viteae. Among all the synthesized compounds, only 12 compounds, namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i, and 7h, have exhibited either >90% micro- or macrofilaricidal activity or sterlization of female worms. These compounds have also been screened against Litomosoides carinii, and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure-activity relationship (SAR) associated with position 1 and 3 substituents in beta-carbolines has been discussed. It has been observed that the presence of a carbomethoxy at position 3 and an aryl substituent at position 1 in beta-carbolines effectively enhances antifilarial activity particularly against A. viteae. Among the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (4c) has shown the highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3, 4-b]indole-3-carboxylate (3a) has shown the highest microfilaricidal action against A. viteae at 50 mg/kg x 5 days (ip). Another derivative of this compound, namely 1-(4-chlorophenyl)-3-(hydroxymethyl)-9H-pyrido[3,4-b]indole (5a), exhibited the highest activity against L. carinii at 30 mg/kg x 5 days (ip) and against B. malayiat 50 mg/kg x 5 days (ip) or at 200 mg/kg x 5 days (po).

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The effect of alkali metal and silver cationization on the collision-induced dissociation (CID) of loganin (1), epi-loganin (2) and ketologanin (3) is discussed. Their protonated molecular ions fragment mainly by glycosidic cleavages. The epimeric pairs (1 and 2) show differences in the abundances of the resulting fragment ions. Lithium cationization induces new dissociation pathways such as the retro-Diels-Alder (RDA) fragmentation followed by rearrangement. Unlike the dissociation of protonated molecular ions, the dissociation of lithiated molecules also provides lithiated sugar fragments. The CID of dilithiated molecules is substantially different from that of the monolithiated precursors. RDA reaction appears to be favoured by the presence of the additional lithium atom in the molecule. In addition, other ring cleavages are also induced. The abundances of the various fragment ions are different in the CID spectra of the epimeric pairs. Extensive D labelling and (6)Li labelling experiments confirmed many of the ion structures proposed. The CID spectra of the sodiated ions are generally weaker, although similar to those of the corresponding lithiated species. Higher alkali metal ion (K(+), Rb(+) and Cs(+)) adducts generated only the corresponding metal ions as products of CID. Similar fragmentations were also observed in the CID of the [M + Ag](+) ions of these compounds, the epimeric pairs showing characteristic differences in their CID behaviour. Copyright 2000 John Wiley & Sons, Ltd.