Discovery of penipanoid C-inspired 2-(3,4,5-trimethoxybenzoyl)quinazolin-4(3H)-one derivatives as potential anticancer agents by inhibiting cell proliferation and inducing apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and the fourth leading cause of cancer-related death worldwide. First-line drugs such as sorafenib provide only a modest benefit to HCC patients. In this study, the gram-scale synthesis of 2-benzoylquinazolin-4(3H)-one skeleton was achieved successfully via the I2/DMSO catalytic system. A series of penipanoid C-inspired 2-(3,4,5-trimethoxybenzoyl)quinazolin-4(3H)-one derivatives was synthesized and evaluated for their cytotoxic activities against four cancer cell lines, HepG2, Bel-7402, A549, and U251. Among these compounds, 4a was the most effective one with IC50 values of 1.22 µM and 1.71 µM against HepG2 and Bel-7402 cells, respectively. Mechanistic studies showed that 4a inhibited hepatocellular carcinoma cell proliferation via arresting cell cycle. Additionally, 4a induced HepG2 cells apoptosis by inducing reactive oxygen species production and elevating the expression of apoptosis-related proteins. More importantly, 4a displayed significant in vivo anticancer effects in the HepG2 xenograft models. This suggests that 4a is a promising lead compound with the potential to be developed as a chemotherapy agent for hepatocellular carcinoma.

[Impact of pregnancy terminations before 28 weeks of gestation on the overall prevalence of neural tube defects in two counties of Shanxi province].

OBJECTIVE: To examine the impact of pregnancy termination before 28 weeks of gestation on the overall prevalence of neural tube defects (NTDs). METHODS: Data collected during the period of 2004 and 2010 from a birth defects surveillance system in Pingding county and Taigu county of Shanxi province were used. Number of births≥28 weeks of gestation and number of cases with major birth defects among the births were collected. Terminations of pregnancies before 28 weeks of gestation due to prenatal diagnosis were also collected. The total prevalence of neural tube defects, prevalence before 28 weeks of gestation, and prevalence of ≥28 weeks gestation were calculated using the total number of pregnancies of ≥28 weeks of gestation as denominator. The prevalence data were compared to examine the impact of pregnancy termination on the total prevalence. The proportions of pregnancy terminations before 28 weeks of gestation due to prenatal diagnosis of an NTD against the total number of NTD cases were also calculated. RESULTS: During 2004-2010, 52 366 births were recorded, and 485 NTD cases were ascertained. The overall prevalence of NTDs was 92.6 per 10,000 births, with prevalence of <28 weeks gestation due to pregnancy terminations as 60.9 per 10,000 births, while the prevalence of ≥28 weeks of gestation was 31.7 per 10,000 births. NTD prevalence of ≥28 weeks gestation was 66.0% lower than the total NTD prevalence. In the last two years, the proportion of NTDs ascertained ≥28 weeks gestation accounted for about 40.0% of the total NTD cases. CONCLUSION: A birth-defect-surveillance program that covered only pregnancies≥28 weeks of gestation resulted in a severe underestimation of the total birth prevalence of NTDs, especially for anencephaly. We would recommend that the current national birth defects surveillance system should include pregnancy terminations before 28 weeks of gestation and the calculation of total NTD prevalence should also include these cases into the numerator, so as to better estimate true population NTD prevalence, upon which the related public health policy is based.

[Prevalence of major external birth defects in high and low risk areas in China, 2003].

OBJECTIVE: To study the prevalence rates of birth defects in high and low risk areas in China. METHODS: A population-based surveillance system on birth defects was used to obtain the prevalence rates of 24 kinds of major external birth defects from > or = 20 weeks of gestation to 7 days of life in selected areas in Shanxi and Jiangsu provinces. RESULTS: The birth prevalence of birth defects (232.4 per 10,000 births) and neural tube defects (NTDs) (138.7 per 10,000 births) in four counties of Shanxi province were significantly higher than that in Taiyuan city (75.3 and 28.2 per 10,000 births, respectively). There was no significant difference for all selected birth defects between Wuxi city and Xishan counties in low risk areas. There was a 6.1-fold of higher prevalence for NTDs in Taiyuan city compared with that in Wuxi areas (4.6 per 10,000 births). In four counties of Shanxi province, the prevalence rates of anencephaly, spina bifida, hydrocephaly, cleft palate alone and polydactyly were significantly higher than in Wuxi areas. The NTDs prevalence rate in four counties of Shanxi was 30.2 times higher than in Wuxi areas. When compared with previous surveillance data, the NTDs prevalence rate did not present obvious declining trend in high risk areas. The birth prevalence rate had a 31.8% decrease when births were calculated after 28 gestational weeks and compared with those from 20 gestational weeks. CONCLUSION: NTDs remained to be the most common birth defect seen in Shanxi province. The birth prevalence rate of NTDs in some areas of Shanxi province was among the highest that ever reported in the world in comparison with data from other countries and regions. The current prevalence rate in high risk areas in Shanxi province did not clearly show a declining trend. Programs on surveillance and prenatal diagnosis were proved to have made big impact on the rates of major external birth defects.