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Natural quinones and their analogues have attracted growing attention because of their novel anticancer activities. A series of novel isothiazoloquinoline quinone analogues were synthesized and evaluated for antitumor activities against four different kind of cancer cells. Among them, isothiazoloquinolinoquinones inhibited cancer cells proliferation effectively with IC50 values in the nanomolar range, and isothiazoloquinolinoquinone 13a induced the cell apoptosis. Further exploration of possible mechanism of action indicates that 13a not only activates ROS production through NQO1-directed redox cycling but also inhibits the phosphorylation of STAT3. These findings indicate that 13a has potential use for the development of new skeleton drug candidate as an efficient substrate of NQO1 and STAT3 inhibitor.

To investigate whether genetic polymorphisms in the microsomal epoxide hydrolase gene (EPHX1) and the glutathione S-transferase theta1 gene (GSTT1) are associated with low birth weight in neonates.Using standard questionnaires, 246 singleton live born mother-neonates pairs (73 cases were mother-low birth weight neonate pairs and 173 controls were mother-non low birth weight neonate pairs) were investigated by the trained field workers with case-control study at the hospital in Anqing, Anhui Province, China between 1998 and 1999. A total of 246 neonates were genotyped for genetic polymorphisms in the EPHX1 gene and the GSTT1 gene by a polymerase chain reaction-restriction fragment length polymorphism assay. Multiple linear regression models were used to estimate the association of the genetic polymorphisms in the EPHX1 gene and the GSTT1 gene with neonatal low birth weight, adjusting for maternal age, education, parity, neonatal sex and gestational age.EPHX1 His139His homozygote was not associated with low birth weight among neonates, compared with EPHX1 His139Arg heterozygote/Arg139Arg homozygote before and after adjustment confounders. GSTT1 absent genotype group also was not associated with low birth weight among neonates, compared with GSTT1 present genotype group before and after adjustment confounders. When both EPHX1 139 polymorphism and GSTT1 polymorphism were considered, a significant reduction in birth weight was found among neonates with EPHX1 His139His homozygote and GSTT1 absent genotype (OR=3.46, P=0.035).The combination between genetic polymorphisms in the EPHX1 gene and the GSTT1 gene in neonates is significantly associated with neonatal low birth weight.