Photocatalytic degradation of trans-cinnamic, dihydrocinnamic, trans-caffeic, and dihydrocaffeic acids and characterization of the products.

Catalysed degradation of aqueous solutions of cinnamic 1, dihydrocinnamic 2, dihydrocaffeic 3 and trans-caffeic 4 acids in the presence of (TiO2) and UV radiation and the products identified by HPLC, and after treatment with diazomethane by GC-MS have been studied. A pH range of 3 to 11 was used. The four acids, in the presence of TiO2 in the dark, underwent little degradation. Extended irradiation of all the acids in the presence of TiO2 produced complete degradation as shown by TOC measurements. Initially the volume of carbon dioxide produced rose steadily to a constant value.

Chemical kinetics of the photocatalytic degradation of trans-cinnamic, dihydrocinnamic, trans-caffeic, and dihydrocaffeic acids.

Quantitative studies of the catalysed degradation of aqueous solutions of cinnamic 1, dihydrocinnamic 2, trans-caffeic 3 and dihydrocaffeic 4 acids in the presence of TiO2 and UV radiation at pH 3 and 10 are reported. The phenolic and aliphatic unsaturated groups in caffeic acid 3 caused it to be adsorbed more strongly than the phenolic saturated acid 4, and these two acids were much more strongly adsorbed than cinnamic and hydrocinnamic acids. The kinetics of the degradation of each acid has been studied at pH 3 and 10. TIC analysis showed complete mineralisation of the acids after 9 h.

Synthesis, hydroxyl radical production and cytotoxicity of analogues of bleomycin.

Two pyridine analogues of the metal complexing region of the anticancer drug bleomycin and two related but deactivated prodrugs have been linked to a 2,6-diphenylpyridine derivative as a DNA binding unit. The 2,6-diphenylpyridine system is structurally related to known amplifiers of the cytotoxicity of bleomycin. The conjugates were found to bind to DNA more strongly than bleomycin-A2 and were more cytotoxic than the corresponding compounds lacking the DNA binding unit. On exposure of a mixture of cells and prodrugs to hypoxia and then air, the prodrug containing the nitrohistidine unit was not bioreductively activated but the prodrug having an N-oxide group was bioreductively activated. This result represents a novel approach to the improvement of the therapeutic ratio of bleomycin analogues.

Phthalimide analogs of CB 1954: synthesis and bioactivation.

Four novel 4-substituted 5-nitrophthalimides (5-substituted-6-nitro-1,3-dihydro-isoindol-1,3-diones), 6, 7, 10 and 11, and the known 5 are prepared as analogs of the dinitrobenzamide prodrug CB 1954, 1, and considered as potential candidates for gene-directed enzyme prodrug therapy. All the phthalimides are poor substrates for Escherichia coli nitroreductase compared to CB 1954. However, 6, 7, 10 and 11 are reduced by both the human and rat forms of DT-diaphorase; 10 is a particularly good substrate but 7 decomposes in phosphate buffer. A cell-line panel consisting of V79 cells that have been engineered to express various levels of either the human or rat forms of DT-diaphorase in an identical cellular background was used to evaluate these compounds as prodrugs activated by this enzyme. The cytotoxic effect of CB 1954 is proportional to the activity of either the rat or human enzyme but cells expressing the rat enzyme were much more sensitive (10000-fold at higher levels of DT-diaphorase activity) than cells expressing comparable levels of the human enzyme. These results demonstrate that the resistance of human tumors to CB 1954 can be accounted for solely by the kinetic properties of the enzyme for this prodrug. The nitrophthalimide analogs overcome this kinetic failing of CB 1954. However, these compounds are not activated to produce cytotoxicity in these DT-diaphorase-expressing cell lines. It is postulated their reduction products fail to undergo an acylation reaction in a manner analogous to CB 1954. Thus, reduction by DT-diaphorase is not predictive of cytotoxicity in this class of prodrugs.

Synthesis and properties of prodrugs activated in hypoxia to give bleomycin analogues.

Prodrugs bioreductively activated to bleomycin analogues are reported. The production of hydroxyl radicals in the presence of FE(II) and dioxygen by both the prodrugs and the activated products are determined and their in vitro cytotoxicity measured.

Potential bioreductively activated hypoxia probes and post-irradiation radiosensitizers related to NITP.

NITP (1) is an effective marker of hypoxia in tumours for both microscopy and cell sorting studies and, additionally, the compound shows post-irradiation sensitization, probably by inhibition of repair of radiation damage to DNA. However, NITP does not have the substitution pattern which the immunochemical reagents are raised to recognize and the compound has very low solubility in water. We report the synthesis of an isomer (13) of NITP which has the desirable substitution pattern and is also soluble in very weak aqueous base. The successful synthesis of 13 uses a nitrosation and cyclization of a substituted uracil (16), but earlier approaches from 5 and 12 yielded the pyridoxanthine derivative 6. The preparative use of nitro group displacement reactions from 8-nitrocaffeine is shown to be a useful entry to a range of 8-substituted caffeines and is utilized to obtain two derivatives of NITP which carry aliphatic amine chains, i.e. 34 and 35.

Radio-active iodine uptake in vitiligo.

Vitiligo and thyroid disease are commonly associated disorders. Twenty-two clinically euthyroid vitiligo patients were studied for functional assessment of thyroid by radioactive iodine uptake assay. Half of them showed abnormal uptake values at 24 hours. Of these patients, 90% had lower values indicating a tendency towards developing hypothyroid state. Subclinical thyroid dysfunction in vitiligo appears to be an adaptive change.

Adult respiratory distress syndrome following aluminium phosphide ingestion. Report of 4 cases.

Four cases of adult respiratory distress syndrome (ARDS) following aluminium phosphide ingestion (ALP) are being reported. The dose of the intoxicant varied from 2 tablets (6.0 gm) to 3 tablets (9.0 gm). All patients had shock at admission and developed ARDS within 6 hours. The exhalation of Phosphine, (PH3) detected by positive silver nitrate paper test, was the possible noxious triggering factor in our cases. The cases are being reported because of their rare occurrence.

Ear-lobe crease and ear-canal hair as predictors of coronary artery disease in Indian population.

215 patients of different communities were selected randomly to predict the correlation between the ear-lobe crease, ear-canal hair and coronary artery disease. On analysis, it was found that prevalence of the ear-lobe crease increases with advancing age, and the incidence was much more higher in Sindhis in whom the overall incidence of CAD is also significantly high. Bilateral diagonal ear-lobe crease was found to be significantly (P less than 0.001) associated in patients with documented CAD, and a significant difference was also observed between men with and without CAD in the presence of ear-canal hair with age matched group. The combined presence of ear-lobe crease and ear-canal hair was more definite and more sensitive index of underlying CAD.