Toll-like receptor 7 mRNA is reduced in hepatitis C-based liver cirrhosis and hepatocellular carcinoma, out-performs alpha-fetoprotein levels, and with age and serum aspartate aminotransferase is a new diagnostic index.

BACKGROUND: Hepatitis B and C viruses are leading causes of liver cirrhosis and hepatocellular carcinoma (HCC). Toll-like receptor 7 (TLR-7) has been implicated in the pathogenesis of HCC linked to hepatitis B. We hypothesised a role of leukocyte TLR-7 mRNA in hepatitis C related liver cirrhosis and HCC, using alpha-fetoprotein (AFP) and liver function tests as comparators. METHODS: We recruited 102 patients with HCV-related HCC, 97 with HCV-related liver cirrhosis and 60 healthy controls. Quantification of TLR-7 mRNA was performed using real-time PCR, AFP and routine LFTs by standard techniques. RESULTS: TLR-7 mRNA levels were significantly lower in HCC patients compared to cirrhotic patients and lower again in healthy controls (p < 0.001 for trend). In multivariate analysis, age, aspartate transaminase (AST), AFP, and TLR-7 mRNA were significant predictors of HCC. The ROCC/AUC for age, AST and TLR-7 mRNA were all between 0.64 and 0.78 (all P < 0.01), but for AFP was 0.57 (95% CI 0.48-0.65, P = 0.09). We derived an index score using age, AST and TLR-7 mRNA for the diagnosis of HCC. The ROCC/AUC for the index was superior to all three root indices in the prediction of HCC. The index linked significantly with the Tokyo and Vienna liver cancer staging systems, but not with those of the CLIP and Okuda systems, in distinguishing HCC from liver cirrhosis. CONCLUSION: The combination of TLR-7 mRNA levels with age and AST improves the performance of TLR-7 in HCC diagnosis, out-performs alpha-fetoprotein and predicts early HCC.

Synthesis and anticonvulsant properties of some novel quinazolinone thiazolidine and 4-thiazolidone derivatives.

A series of quinazolinone thiazolidine and 4-thiazolidone derivatives were prepared. The structure of the isolated products have been confirmed by elemental analyses, spectroscopic data and ambiguous synthesis in certain cases. Some of these compounds were effective against seizures induced by pentetrazol.

Synthesis and antifungal activity of some imidazo, pyrazino and v-triazoloquinoxalines.

The reaction of 6,7-diamino-1,4-diethyl-11-quinoxaline-1 H,4H-2,3-dione (1) with aliphatic and aromatic carboxylic acids in the presence and absence of an acid catalyst affords 2-alkyl- and 2-aryl-5,8-diethyl-imidazo[4,5-g]quinoxaline-5 H,8 H-6,7-diones 2a-1. Cyclization of 1 with carbon disulphide in basic medium yields 2-mercapto-5,8-diethyl-imidazo[4,5-g]-quinoxaline-5 H,8 H-6,7-dione (4) which on reactions with methyl iodide and substituted benzyl halides give the S-substituted derivatives 5a-f. Condensation of 1 with 1,2-diketones yields the corresponding pyrazinoquinoxalines 6a-e. v-Triazoloquinoxaline 7 is obtained by cyclization of 1 with nitrous acid. Compounds 2a-1, 5a-f and 6a-3 exhibit moderate to weak antifungal activity.

Synthesis and antiinflammatory properties of some novel thiazolidinones and imidazolidinones derived from 4-(3-phenyl-4(3H)-quinazolinon-2-yl)-3-thiosemicarbazone.

A series of quinazolinone thiazolidinone and imidazolidinone derivatives were prepared. These compounds were evaluated for their antiinflammatory activity. The most active compounds (6b, 6c and 6d) were found to be superior to phenylbutazone as they were devoid of any ulcerogenic activity.

Synthesis and antihypertensive activity of novel 1-(4-benzyl-1-phthalazinyl)-pyrazolo[3,4-d]pyrimidines.

Convenient Syntheses of derivatives of the pyrazolo[3,4-d]pyrimidines from 1-(4-benzyl-1-phthalazinyl)-3-amino-4-cyano-5-methylpyrazole (1) and carbon disulphide, aryl isothiocyanates, nitriles or guanidine are described. Derivatives of compound 1 undergo cyclization to the titled ring system by action of dimethylformamide dimethylacetal or hydrogen sulphide followed by treatment with triethylamine. Some of the new compounds were studied as antihypertensive agents.

Synthesis and antiinflammatory activity of novel pyrimidine derivatives.

Hydrazinolysis of ethyl [(4-methyl-6-phenylpyrimidin-2-yl)oxy]acetate (1) gives the unexpected bis(4-methyl-6-phenylpyrimidin-2-yl)hydrazine (2). The desired [(4 methyl-6-phenylpyrimidin-2-yl)oxy]acetohydrazide (3) was prepared from the ester (1) with hydrazine in absolute ethanol. Starting from 3, several new hydrazones, 1,3,4 oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles and 1,3-thiazoles have been synthesized. Structure of the new compounds was confirmed by elemental analysis, spectral data and alternative synthesis in certain cases. Some representative examples were evaluated for their antiinflammatory activities.

Synthesis and anticonvulsant properties of some novel quinazolone-thiosemicarbazone and 4-thiazolidone derivatives.

Diverse biological activities have been found in compounds having a quinazolinone ring system. A large number of 4(3H)-quinazolinones, in particular those possessing 2-alkyl-3-aryl, 2,3-dialkyl, and 2-alkyl-3-amino substitution, have been evaluated for pharmacological activity. On the other hand, thiazolidone derivatives are reported to have anesthetic, anticonvulsant, and hypnotic activity.