In our search for novel small molecules activating procaspase-3, we have designed and synthesised a series of novel acetohydrazides incorporating quinazolin-4(3H)-ones (5, 6, 7). Biological evaluation revealed eight compounds with significant cytotoxicity against three human cancer cell lines (SW620, colon cancer; PC-3, prostate cancer; NCI-H23, lung cancer). The most potent compound 5t displayed cytotoxicity up to 5-fold more potent than 5-FU. Analysis of structure-activity relationships showed that the introduction of different substituents at C-6 position on the quinazolin-4(3H)-4-one moiety, such as 6-chloro or 6-methoxy potentially increased the cytotoxicity of the compounds. In term of caspase activation activity, several compounds were found to exhibit potent effects, (e.g. compounds 7 b, 5n, and 5l). Especially, compound 7 b activated caspases activity by almost 200% in comparison to that of PAC-1. Further docking simulation also revealed that this compound potentially is a potent allosteric inhibitor of procaspase-3.

No abstract

The present article describes the synthesis and biological activity of various series of novel hydroxamic acids incorporating quinazolin‐4(3H)‐ones as novel small molecules targeting histone deacetylases. Biological evaluation showed that these hydroxamic acids were potently cytotoxic against three human cancer cell lines (SW620, colon; PC‐3, prostate; NCI−H23, lung). Most compounds displayed superior cytotoxicity than SAHA (suberoylanilide hydroxamic acid, Vorinostat) in term of cytotoxicity. Especially, N‐hydroxy‐7‐(7‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide (5b) and N‐hydroxy‐7‐(6‐methyl‐4‐oxoquinazolin‐3(4H)‐yl)heptanamide (5c) (IC50 values, 0.10–0.16 μm) were found to be approximately 30‐fold more cytotoxic than SAHA (IC50 values of 3.29–3.67 μm). N‐Hydroxy‐7‐(4‐oxoquinazolin‐3(4H)‐yl)heptanamide (5a; IC50 values of 0.21–0.38 μm) was approximately 10‐ to 15‐fold more potent than SAHA in cytotoxicity assay. These compounds also showed comparable HDAC inhibition potency with IC50 values in sub‐micromolar ranges. Molecular docking experiments indicated that most compounds, as represented by 5b and 5c, strictly bound to HDAC2 at the active binding site with binding affinities much higher than that of SAHA.

Six iridoid derivatives (1-6), including two new compounds myrmecodoides A and B (1 and 2), were isolated from the ant-plant Myrmecodia tuberosa. Their structures were determined on the basis of spectroscopic data ((1)H and (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, NOESY and HR-ESI-MS) and by comparison with the literature values. Among isolates, 3 and 4 exhibit weak antibacterial effect against Staphylococcus aureus subsp. aureus with MIC value of 100.0 μg/mL.

Water hyacinth (WH) biomass is one of the popular materials in the Vietnamese Mekong Delta, a potential substrate for biogas production. The effectiveness of utilizing WH for producing biogas under anaerobic digestion was demonstrated in the previous studies, but the research was focused on the loading rate of about 1.0% volatile solid (VS). Therefore, in the present study, a semi-continuous anaerobic digestion experiment was conducted with the five levels of VS, including 1.0%VS, 1.5%VS, 2.0%VS, 2.5%VS, and 3.0%VS, to examine how loaded VS can affect biogas production. Each treatment was designed with three replications over 60 days. The measured parameters included pH, temperature (Temp; °C), redox potential (Eh; mV), daily produced biogas volume (L), cumulative biogas volume (L), and methane (CH 4 ) concentration (%) during the 60 days of the experiment. The obtained results showed that pH, tempt, and Eh parameters did not negatively affect biogas production. However, the volume of daily biogas in the treatment of 3.0%VS was higher than in other treatments. In addition, the cumulative biogas volume in the treatment of 3.0%VS was the highest and significantly different between all reactors (p<0.05). Meanwhile, the treatment of 1.0%VS was known with the lowest values. The study explored that the volume of biogas could be increased when the organic loading rate VS is increased.