Design, Synthesis, Structure-Activity Relationship and Docking Studies of Novel Functionalized Arylvinyl-1,2,4-Trioxanes as Potent Antiplasmodial as well as Anticancer Agents.

A novel series of synthetic functionalized arylvinyl-1,2,4-trioxanes (8 a-p) has been prepared and assessed for their in vitro antiplasmodial activity against the chloroquine-resistant Pf INDO strain of Plasmodium falciparum by using a SYBR green-I fluorescence assay. Compounds 8 g (IC50 =0.051 µM; SI=589.41) and 8 m (IC50 =0.059 µM; SI=55.93) showed 11-fold and >9-fold more potent antiplasmodial activity, respectively, as compared to chloroquine (IC50 =0.546 µM; SI=36.63). Different in silico docking studies performed on many target proteins revealed that the most active arylvinyl-1,2,4-trioxanes (8 g and 8 m) showed dihydrofolate reductase (DHFR) binding affinities on a par with those of chloroquine and artesunate. The in vitro cytotoxic potentials of 8 a-p were also evaluated against human lung (A549) and liver (HepG2) cancer cell lines along with immortalized normal lung (BEAS-2B) and liver (LO2) cell lines. Following screening, five derivatives viz. 8 a, 8 h, 8 l, 8 m and 8 o (IC50 =1.65-31.7 µM; SI=1.08-10.96) were found to show potent cytotoxic activity against (A549) lung cancer cell lines, with selectivity superior to that of the reference compounds artemisinin (IC50 =100 µM), chloroquine (IC50 =100 µM) and artesunic acid (IC50 =9.85 µM; SI=0.76). In fact, the most active 4-naphthyl-substituted analogue 8 l (IC50 =1.65 µM; SI >10) exhibited >60 times more cytotoxicity than the standard reference, artemisinin, against A549 lung cancer cell lines. In silico docking studies of the most active anticancer compounds, 8 l and 8 m, against EGFR were found to validate the wet lab results. In summary, a new series of functionalized aryl-vinyl-1,2,4-trioxanes (8 a-p) has been shown to display dual potency as promising antiplasmodial and anticancer agents.

[Effect of integrated schistosomiasis control in Honghu City from 2008 to 2018].

OBJECTIVE: To evaluate the effect of integrated schistosomiasis control measures in Honghu City during the period from 2008 through 2018. METHODS: The data pertaining to schistosomiasis control measures and the endemic situation of schistosomiasis in Honghu City were collected from 2008 to 2018, and the effect of integrated schistosomiasis control measures implemented was evaluated. RESULTS: The resources from agriculture, water resources, forestry, land, education and communication sectors were integrated to implement the integrated schistosomiasis control strategy with the focus on the control of source of Schistosoma japonicum infection in Honghu City from 2008 to 2018. The prevalence of S. japonicum infection reduced from 3.03% in 2008 to 0 in 2018 in humans in the city, and no acute infection was detected since 2009. In addition, the prevalence of S. japonicum infection in cattle reduced from 2.85% in 2008 to 0 in 2018, and no snail infection was found since 2012. Transmission control of schistosomiasis was achieved in the city in 2013, and transmission interruption was achieved in 2018. CONCLUSIONS: The integrated schistosomiasis control measures achieve remarkable effects in Honghu City; however, there is still a risk of schistosomiasis transmission.

Effect of integrated schistosomiasis control in Honghu City from 2008 to 2018 / 中国血吸虫病防治杂志

Objective To evaluate the effect of integrated schistosomiasis control measures in Honghu City during the period from 2008 through 2018. Methods The data pertaining to schistosomiasis control measures and the endemic situation of schistosomiasis in Honghu City were collected from 2008 to 2018, and the effect of integrated schistosomiasis control measures implemented was evaluated. Results The resources from agriculture, water resources, forestry, land, education and communication sectors were integrated to implement the integrated schistosomiasis control strategy with the focus on the control of source of Schistosoma japonicum infection in Honghu City from 2008 to 2018. The prevalence of S. japonicum infection reduced from 3.03% in 2008 to 0 in 2018 in humans in the city, and no acute infection was detected since 2009. In addition, the prevalence of S. japonicum infection in cattle reduced from 2.85% in 2008 to 0 in 2018, and no snail infection was found since 2012. Transmission control of schistosomiasis was achieved in the city in 2013, and transmission interruption was achieved in 2018. Conclusions The integrated schistosomiasis control measures achieve remarkable effects in Honghu City; however, there is still a risk of schistosomiasis transmission.

Effect of integrated schistosomiasis control in Honghu City from 2008 to 2018 / 中国血吸虫病防治杂志

Objective To evaluate the effect of integrated schistosomiasis control measures in Honghu City during the period from 2008 through 2018. Methods The data pertaining to schistosomiasis control measures and the endemic situation of schistosomiasis in Honghu City were collected from 2008 to 2018, and the effect of integrated schistosomiasis control measures implemented was evaluated. Results The resources from agriculture, water resources, forestry, land, education and communication sectors were integrated to implement the integrated schistosomiasis control strategy with the focus on the control of source of Schistosoma japonicum infection in Honghu City from 2008 to 2018. The prevalence of S. japonicum infection reduced from 3.03% in 2008 to 0 in 2018 in humans in the city, and no acute infection was detected since 2009. In addition, the prevalence of S. japonicum infection in cattle reduced from 2.85% in 2008 to 0 in 2018, and no snail infection was found since 2012. Transmission control of schistosomiasis was achieved in the city in 2013, and transmission interruption was achieved in 2018. Conclusions The integrated schistosomiasis control measures achieve remarkable effects in Honghu City; however, there is still a risk of schistosomiasis transmission.