One-Pot Microwave Synthesis of Pyrimido[4,5-b]quinoline and its C- and S-Glycosides with Anti-Inflammatory and Anticancer Activities

An efficient one-pot synthesis of 2-thioxopyrimido[4,5-b]quinoline 3a,b has been accomplished from a three-component reaction of 6-aminothiouracil, cyclohexanone and aromatic aldehyde under microwave irradiation. Compound 3a,b was used as a key intermediate for the synthesis of S- and C-nucleoside analogs of types, 5-(4-fluorophenyl / 4-anisyl)-2-S-(β-D-ribofuranosyl / arabinofuranosyl)-6,7,8,9-tetrahydro-3H-pyrimido[4,5-b]quinolin-4-one (6a–d) and 5-(4-fluorophenyl / 4-anisyl)-2-S-(β-D-gluco / galactopyranosyl)-6,7,8,9-tetrahydro-3H-pyrimido[4,5-b]quinolin-4-one (8a–d). Also. the 2-hydrazino compounds 9a,b were used for the synthesis of 3-(glycosyl)-6-(4-substituted phenyl)-7,8,9,10-tetrahydro[1,2,4]triazolo[4\u27,3\u27:1,2]pyrimido[4,5-b]quinoline-5-(1H)-one (11a–d and 13a–d). The title compounds were investigated for anti-inflammatory and anticancer activities. Compounds 11a exhibited the comparable anti-inflammatory activity (83.4 %) to the standard drug Indomethacin (85.2 %). 5-(4-Fluorophenyl)-2-S-(β-D-ribofuranosyl)-6,7,8,9-tetrahydro-3H-pyrimido[4,5-b]quinolin-4-one 6a and 3-(ribosyl)-5-(4-fluorophenyl)-7,8,9,10-tetrahydro[1,2,4]triazolo[4\u27,3\u27:1,2]pyrimido[4,5-b]quinolin-5-one (13a) exhibited the maximum cytotoxic effect against the three human cancer cell lines with inhibitory effects higher than the reference doxorubicin. This work is licensed under a Creative Commons Attribution 4.0 International License

Copro-diagnosis of Echinococcus granulosus infection in dogs by amplification of a newly identified repeated DNA sequence.

International audienceDiagnosis of Echinococcus granulosus infection in dogs by detecting adult worms recovered post mortem or purged from the intestines after treatment with arecoline is not suitable for mass screening. Large-scale diagnosis by detection of copro-antigens is useful but only with relatively high intensity infections, and only by genus. To provide a more sensitive and specific diagnosis, a polymerase chain reaction (PCR) assay was developed, that amplified a target repeated sequence (EgG1 Hae III) newly identified in the genome of the common sheep strain of E. granulosus. This repeated sequence consists of approximately 6,900 copies, arranged in tandem, in groups of 2-6 repeats. The corresponding primers used in the PCR easily detected a single egg with no cross-amplification of DNA from closely related cestodes, including E. multilocularis and Taenia spp. Fecal samples from naturally infected dogs, with 2-10,000 E. granulosus worms at necropsy, were all PCR positive, while E. multilocularis or Taenia spp. positive controls as well as non-endemic controls were all PCR negative. This copro-PCR assay was demonstrated to be 100% specific and also detected all necropsy-positive E. granulosus-infected dogs. It is suggested that this copro-PCR assay has the potential for pre-mortem diagnosis of E. granulosus infection even in areas where E. granulosus and E. multilocularis are co-endemic