Synthesis,Biological Evaluation,and Docking Study of Ring-Opening Amide Analogs of Matrine as Antitumor Agents

In this article, we designed and synthesized two series of matrine analogs with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N-(3-bromophenyl)-4-[(1R,3aS,10aR,10bS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl]butanamide ( B11 ) with a meta-bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,10aR,10bS)-1-[4-(3-bromoanilino)-4-oxobutyl]octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo.     

Pitavastatin in cardiometabolic disease: therapeutic profile

Statins effectively lower low-density lipoprotein-cholesterol (LDL-C) and reduce cardiovascular risk in people with dyslipidemia and cardiometabolic diseases such as Metabolic syndrome (MetS) or type 2 diabetes (T2D). In addition to elevated levels of LDL-C, people with these conditions often have other lipid-related risk factors, such as high levels of triglycerides, low levels of high-density lipoprotein-cholesterol (HDL-C), and a preponderance of highly atherogenic, small, dense low-density lipoprotein particles. The optimal management of dyslipidemia in people with MetS or T2D should therefore address each of these risk factors in addition to LDL-C. Although statins typically have similar effects on LDL-C levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects, adverse event profiles and drug-drug interactions. The choice of statin should therefore depend on the characteristics and needs of the individual patient. Compared with other statins, pitavastatin has distinct pharmacological features that translate into a broad range of actions on both apolipoprotein-B-containing and apolipoprotein-A-containing lipoproteins. Studies show that pitavastatin 1 to 4 mg is well tolerated and significantly improves LDL-C and triglyceride levels to a similar or greater degree than comparable doses of atorvastatin, simvastatin or pravastatin, irrespective of diabetic status. Moreover, whereas most statins show inconsistent effects on HDL-C levels, pitavastatin-treated patients routinely experience clinically significant elevations in HDL-C that are maintained and even increased over the long term. In addition to increasing high-density lipoprotein quantity, pitavastatin appears to improve high-density lipoprotein function and to slow the progression of atherosclerotic plaques by modifying high-density lipoprotein-related inflammation and oxidation, both of which are common in patients with MetS and T2D. When choosing a statin, it is important to note that patients with MetS have an increased risk of developing T2D and that some statins can exacerbate this risk via adverse effects on glucose regulation. Unlike many statins, pitavastatin appears to have a neutral and even beneficial effect on glucose regulation, making it a useful treatment option in this high-risk group of patients. Together with pitavastatin’s beneficial effects on the cardiometabolic lipid profile and its low potential for drug-drug interactions, this suggests that pitavastatin might be a useful lipid-lowering option for people with cardiometabolic disease.     

Wastewater: A Potential Bioenergy Resource

Wastewaters are a rich source of nutrients for microorganisms. However, if left unattended the biodegradation may lead to severe environmental hazards. The wastewaters can thus be utilized for the production of various value added products including bioenergy (H₂ and CH₄). A number of studies have reported utilization of various wastewaters for energy production. Depending on the nature of the wastewater, different reactor configurations, wastewater and inoculum pretreatments, co-substrate utilizations along with other process parameters have been studied for efficient product formation. Only a few studies have reported sequential utilization of wastewaters for H₂ and CH₄ production despite its huge potential for complete waste degradation.     

Ethylene and IAA interactions in the inhibition of photoperiodic flower induction of <Emphasis Type="Italic">Pharbitis nil</Emphasis>

It has been shown that both IAA and ethylene application inhibit flower induction in the short-day plant Pharbitis nil. However application of IAA has elevated ethylene production in this plant, as well. Strong enhancement of ethylene production is also correlated with the night-break effect, which completely inhibits flowering. In order to determine what the role of IAA and ethylene is in the photoperiodic flower induction in Pharbitis nil, we measured changes in their levels during inductive and non-inductive photoperiods, and the effects of ethylene biosynthesis and action inhibitors on inhibition of flowering by IAA. Our results have shown that the inhibitory effect of IAA on Pharbitis nil flowering is not physiological but is connected with its effect on ethylene biosynthesis.     

INFOS: spectrum fitting software for NMR analysis

Software for fitting of NMR spectra in MATLAB is presented. Spectra are fitted in the frequency domain, using Fourier transformed lineshapes, which are derived using the experimental acquisition and processing parameters. This yields more accurate fits compared to common fitting methods that use Lorentzian or Gaussian functions. Furthermore, a very time-efficient algorithm for calculating and fitting spectra has been developed. The software also performs initial peak picking, followed by subsequent fitting and refinement of the peak list, by iteratively adding and removing peaks to improve the overall fit. Estimation of error on fitting parameters is performed using a Monte-Carlo approach. Many fitting options allow the software to be flexible enough for a wide array of applications, while still being straightforward to set up with minimal user input.     

Anatomy of the antennal dorsal organ in female of Neodryinus typhlocybae (Hymenoptera: Dryinidae): A peculiar sensory structure possibly involved in perception of host vibration

Neodryinus typhlocybae (Hymenoptera: Dryinidae) is a natural enemy of the planthopper Metcalfa pruinosa, which was introduced from North America into Europe and has become established in various regions as a pest species. Vibrational signals play a crucial role in the communication of M. pruinosa, which appears to be exploited by N. typhlocybae. Scanning and transmission electron microscopy have shown that the antennae of N. typhlocybae females have peculiar and complex sensory structures: deep longitudinal grooves that house long sensilla trichodea, termed here “Antennal Dorsal Organs.” Such structures were not present on male antennae. These sensilla extend for the length of the grooves, without contact with the groove cuticle. Their hair shaft is empty and aporous, and inserted into a specialized socket, underneath which there is a cuticular ampulla‐like chamber. Each sensillum is associated with two sensory neurons: one terminates at the proximal end of the dendritic sheath; the other continues into the sensillum sinus and is enclosed in the dendritic sheath. This second sensory neuron then enters the ampulla‐like chamber through the circular opening, and then terminates with a conspicuous tubular body at the shaft base. The possible involvement of this peculiar structure in the context of host recognition mechanism is discussed. J. Morphol. 277:128–137, 2016. © 2015 Wiley Periodicals, Inc.