Synthesis and biological effects evaluation of benzoconduritols C and D from oxabenzonorbornadiene

Within the Superfund ecological risk assessment process, soils represent not only complex contaminant sources but also complex exposure systems. Hence, soil contamination evaluations relevant to ecological risk assessments for Superfund sites must consider various routes and sources of exposure, as well as biological targets representative of various plant, animal, and microbial species. Within ecological contexts, biological evaluations in the field and laboratory should be considered critical components in the ecological risk assessment process, since integrated approaches to hazard evaluation consider contaminant bioavailability and subtle expressions of adverse biological effects associated with chronic exposures. Depending upon habitat type -- freshwater, marine and estuarine, wetland, or terrestrial -- field and laboratory methods have been developed for hazard evaluation which lend themselves directly to the Superfund ecological risk assessment process. For example, in various mining districts in the western United States, riparian wetlands are frequently impacted by heavy metal-laden sediments. The present study illustrates preliminary work within a Superfund ecological risk assessment for such a heavy metal-impacted riparian wetland in western Montana. A variety of biological test methods (e.g., terrestrial and aquatic tests) were critical to the wetland evaluation, and in conjunction with chemical analyses, these biological and ecological evaluations yielded an integrated assessment of heavy metal effects on the wetland, and assured that environmental decisions regarding the wetland could be made with reduced uncertainty.

This Special Issue (SI), titled "Medical Value of Metal Complexes and Plant-Derived Compounds: Biological Evaluation, Health Effects, Challenges, and Future Opportunities", aims to include reports updating our knowledge about the effects of exposure to prevalent heavy metals in the environment, which adversely affect animal and human health [...].

Historically, natural products have played a major role in the development of antibiotics. Their complex chemical structures and high polarity give them advantages in the drug discovery process. In the broad range of natural products, sesquiterpene lactones are interesting compounds because of their diverse biological activities, their high-polarity, and sp3-carbon-rich chemical structures. Parthenolide (PTL) is a natural compound isolated from Tanacetum parthenium, of the family of germacranolide-type sesquiterpene lactones. In recent years, parthenolide has been studied for its anti-inflammatory, antimigraine, and anticancer properties. Recently, PTL has shown antibacterial activities, especially against Gram-positive bacteria. However, few studies are available on the potential antitubercular activities of parthenolide and its analogs. It has been demonstrated that parthenolide's biological effects are linked to the reactivity of α-exo-methylene-γ-butyrolactone, which reacts with cysteine in targeted proteins via a Michael addition. In this work, we describe the ene reaction of acylnitroso intermediates with parthenolide leading to the regioselective and stereoselective synthesis of new derivatives and their biological evaluation. The addition of hydroxycarbamates and hydroxyureas led to original analogs with higher polarity and solubility than parthenolide. Through this synthetic route, the Michael acceptor motif was preserved and is thus believed to be involved in the selective activity against Mycobacterium tuberculosis.

Weaning food was formulated using a cassava product, 'Tapioca' (TAP), supplemented with roasted-sprouted soybeans (SS), with and without additional (10%) malted sorghum flour (MS). Biological evaluation was carried out on the formulations using 4-5 week old weanling albino rats, with Cerelac (a commercial maize-milk weaning food) as the control diet. There were increases in growth rate of rats fed with both the test and control diets. There were no significant (p >0.05) differences between the test diets and control diet in true digestibility values. The biological value (BV) and net protein utilization (NPU) values for the formulated diets were above the recommended minimum values. The weight of organs (small intestine, pancreas, liver and heart) of rats fed TAP + SS and TAP + SS + MS based diets were not higher than those of organs of rats fed Cerelac. It was concluded that cassava products could potentially be employed successfully in the preparation of weaning foods of comparable quality to available commercial brands.

AhR agonists screening and identification in indoor dust based on non-target chemical analysis by GC-Q-TOFMS and biological effect evaluation referring to ToxCast/Tox21 database

Introduction. The results of 30 years of experience in the development, research, use of food products – dietary supplements-apiphytocompositions, their medical and biological evaluation and effectiveness in medical practice are presented. Apiphytocompositions were used as a food product in the complex therapy of diseases of the gastrointestinal tract, in particular, in patients who lived in areas of radiation control or were exposed to radioactive radiation; in infectious pathology – acute intestinal infections, hepatitis, acute respiratory diseases. The goal of the work. To evaluate medical and biological properties and effectiveness of dietary supplements-apiphytocompositions in medical practice based on thirty years of experience. Materials and methods of research. An analysis of the state of health of people aged 16 to 60 living in environmentally contaminated areas, in radiation control zones, evicted from areas of mandatory and guaranteed resettlement. Determination of incorporated radionuclides was determined by human impulse counter (QBM-1). Determination of the content of lipid peroxidation products and superoxide dismutase activity in the blood was performed according to standard methods. Results of research and discussion. Over 30 years, more than 20 combined food products of dietary supplements-apiphytocompositions therapeutic and prophylactic action with the use of economical biotechnology. They were used by patients as an additional food product in combination with evidence-based medicine protocols in the complex therapy of humans. The results of the study revealed their positive effect on the human body. Conclusions and prospects for further research. Developed food products – dietary supplements-apiphytocomposition can be used both for monotherapy and in combination with evidence-based medicine protocols in complex therapy of humans.

The objective of this work was to evaluate the biological effect of the secondary effluent (SE) of a wastewater treatment plant and reclaimed water treated via ultrafiltration (UF) followed by either reverse osmosis (RO) membrane filtration or nanofiltration (NF) to be used for environmental use by comparing the results of algal growth inhibition tests of concentrated samples of the SE and permeates of RO and NF with those of six rivers in southern Okinawa Island. Although the SE water had no adverse effects on the growth of the algae Pseudokirchneriella subcapitata, it could lead to water quality degradation of rivers in terms of its toxic unit value, whereas the use of RO and NF permeates would not lead to such degradation. The recharge of rivers, into which domestic wastewater and livestock effluents might be discharged in southern Okinawa Island, with reclaimed water subjected to advanced treatment could dilute the concentrations of chemicals that cause biological effects and improve the water quality of the rivers, based on the results of the bioassay using P. subcapitata. Comparing the results of bioassays of reclaimed water with those of the ambient water at a site might be effective in assessing the water quality of reclaimed water for environmental use at the site.

PurposeWe explored the effect of hepatocyte growth factor (HGF)/Met signaling pathway on nasopharyngeal carcinoma (NPC) cells in vitro and in vivo, and investigated the ability of Met tyrosine kinase inhibitor (TKI) to block HGF-induced biological signaling.Experimental designMet TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo. HGF/Met expression and activation of signaling in NPC cells were detected by using Western blot and immunohistochemistry. Biological evaluation, including wound healing, cell proliferation, and invasion of NPC cells, was also examined, and the correlation between HGF/Met expression of primary and metastatic tumor in NPC patients and clinical prognosis were also analyzed.ResultsMet TKI inhibitor, PF-2341066, inhibited growth of NPC cells in vivo with half maximal inhibitory concentration of 0.79±0.21 μmol/L, and suppressed invasion and migration of NPC cells; also, the inhibition of PF-2341066 was synergized with cisplatin treatment. Compared with the control group, Met TKI inhibited metastasis of transplanted NPC in nude mice (the number of live metastases [mean ± SD]: 5.8±2.2 versus 11.8±2.2, P=0.03; the number of lung metastases: 2.3±1.5 versus 5.3±0.9, P=0.06). HGF was widely expressed in both primary and metastatic lesions while Met expression of metastatic lesions was higher than that of primary lesions (primary lesions: 24.7%; liver metastases: 40%; lung metastases: 29%; lymph node metastases: 29%, P<0.05), and overall survival of NPC patients with higher expression of Met was shorter (P=0.13).ConclusionOur results demonstrated that HGF/Met signaling promoted NPC growth, further resulting in metastasis and poor prognosis. Met TKI, PF-2341066, showed potent antitumor activity in vivo and in vitro which was enhanced by combination with cisplatin. Our study implied that HGF/Met signaling was the potential therapeutic target in NPC, and blockage of the signaling could prevent growth and metastasis of NPC and derive clinical benefit.

Citrus junos Seib ex TANAKA possesses various biological effects. It has been used in oriental remedies for blood circulation and the common cold. Recently, biological effects of C. junos peel have been reported. However, optimization of the biological properties of C. junos peel preparations has yet to be reported on. We developed a high-performance liquid chromatography (HPLC) method for quantification of the active constituents in C. junos peel. Hot water and ethanolic extracts of C. junos peel were prepared and their chemical profiles and biological activities were evaluated. The 80% ethanolic extract demonstrated the greatest antioxidant activity and phenolic content, while the 100% ethanolic extract had the greatest xanthine oxidase inhibitory activity. Elastase inhibition activity was superior in aqueous and 20% ethanolic extracts. The contents of two flavonoids were highest in the 100% ethanolic extract. We postulated that the antioxidant and anti-aging effects of C. junos peel extract could be attributed to phenolics such as flavonoids. Our results suggest that the flavonoid-rich extract of C. junos may be utilized for the treatment and prevention of metabolic disease and hyperuricemia while the water-soluble extract of C. junos could be used as a source for its anti-aging properties.

Molecular docking studies of the interaction between propargylic enol ethers and human DNA topoisomerase IIα

Kynurenic acid (KYNA) is an endogenous neuroprotective agent of increasing importance. Several derivatives have already been synthesized, bearing an abundance of functional groups attached to the main skeleton in different positions. Several of these compounds have already been tested in biological evaluations, with several of them targeting the same receptors and biological effects as KYNA. However, these modified compounds build upon the unmodified KYNA skeleton leaving a possible route for the synthesis of new, potentially neuroprotective derivatives with heteroatom-containing ring systems. The aim of this review is to summarize the syntheses of KYNA derivatives with altered skeletons and to pinpoint an appealing transformation for future medicinal lead molecules.

Phenolic acids have recently gained considerable attention because of their numerous practical, biological, and pharmacological benefits. Various polyphenolic compounds are widely distributed in plant sources. Flavonoids and phenolic acids are the two main polyphenolic compounds that many plants contain abundant polyphenols. Chlorogenic acid, one of the most abundant phenolic acids, has various biological activities, but it is chemically unstable and degrades into other compounds or different enzymatic processes. In this review, we have studied many publications about CA and its derivatives. CA derivatives were classified into three categories in terms of structure and determined each part's effects on the body. The biological evaluations, structure-activity relationship, and mechanism of action of CA derivatives were investigated. The search databases for this review were ScienceDirect, Scopus, Pub- Med and google scholar. Many studies have reported that CA derivatives have demonstrated several biological effects, including anti-oxidant, anti-inflammatory, anti-microbes, anti-mutation, anti-carcinogenic, anti-viral, anti-hypercholesterolemia, anti-hypertensive, anti-bacterial, and hypoglycemic actions. The synthesis of new stable CA derivatives can enhance its metabolic stability and biological activity. The present study represented different synthetic methods and biological activities of CA derivatives. These compounds showed high antioxidant activity across a wide range of biological effects. Our goal was to help other researchers design and develop stable analogs of CA for the improvement of its metabolic stability and the promotion of its biological activity.

Oligopeptide boronates with a lipophilic tail are known to inhibit the type I signal peptidase in E.coli, which is a promising drug target for developing novel antibiotics. Antibacterial activity depends on these oligopeptides having a cationic modification to increase their permeation. Unfortunately, this modification is associated with cytotoxicity, motivating the need for novel approaches. The sulfonimidamide functionality has recently gained much interest in drug design and discovery, as a means of introducing chirality and an imine-handle, thus allowing for the incorporation of additional substituents. This in turn can tune the chemical and biological properties, which are here explored. We show that introducing the sulfonimidamide between the lipophilic tail and the peptide in a series of signal peptidase inhibitors resulted in antibacterial activity, while the sulfonamide isostere and previously known non-cationic analogs were inactive. Additionally, we show that replacing the sulfonamide with a sulfonimidamide resulted in decreased cytotoxicity, and similar results were seen by adding a cationic sidechain to the sulfonimidamide motif. This is the first report of incorporation of the sulfonimidamide functional group into bioactive peptides, more specifically into antibacterial oligopeptides, and evaluation of its biological effects.

Growing experimental evidences suggest the existence of direct relationships between the surface chemistry of nanomaterials and their biological effects. Herein, we have employed computational approaches to design a set of biologically active carbon nanotubes (CNTs) with controlled protein binding and cytotoxicity. Quantitative structure–activity relationship (QSAR) models were built and validated using a dataset of 83 surface-modified CNTs. A subset of a combinatorial virtual library of 240 000 ligands potentially attachable to CNTs was selected to include molecules that were within the chemical similarity threshold with respect to the modeling set compounds. QSAR models were then employed to virtually screen this subset and prioritize CNTs for chemical synthesis and biological evaluation. Ten putatively active and 10 putatively inactive CNTs decorated with the ligands prioritized by virtual screening for either protein-binding or cytotoxicity assay were synthesized and tested. We found that all 10 putatively inactive and 7 of 10 putatively active CNTs were confirmed in the protein-binding assay, whereas all 10 putatively inactive and 6 of 10 putatively active CNTs were confirmed in the cytotoxicity assay. This proof-of-concept study shows that computational models can be employed to guide the design of surface-modified nanomaterials with the desired biological and safety profiles.

The purpose of this study was to find the biological propensities of the vegetable plant Pleurospermum candollei by investigating its phytochemical profile and biological activities. Phytochemical analysis was done by spectroscopic methods to investigate the amount of total polyphenols, and biological evaluation was done by the different antioxidant, enzyme inhibitory (tyrosinase, α-amylase, and α-glucosidase), thrombolytic, and antibacterial activities. The highest amount of total phenolic and flavonoid contents was observed in methanolic extract (240.69 ± 2.94 mg GAE/g and 167.59 ± 3.47 mg QE/g); the fractions showed comparatively less quantity (57.02 ± 1.31 to 144.02 ± 2.11 mg GAE/g, and 48.21 ± 0.75 to 96.58 ± 2.30 mg QE/g). The effect of these bioactive contents was also related to biological activities. GCMS analysis led to the identification of bioactive compounds with different biological effects from methanolic extract (antioxidant; 55.07%, antimicrobial; 56.41%), while the identified compounds from the n-hexane fraction with antioxidant properties constituted 67.86%, and those with antimicrobial effects constituted 82.95%; however, the synergetic effect of polyphenols may also have contributed to the highest value of biological activities of methanolic extract. Molecular docking was also performed to understand the relationship of identified secondary metabolites with enzyme-inhibitory activities. The thrombolytic activity was also significant (40.18 ± 1.80 to 57.15 ± 1.10 % clot lysis) in comparison with streptokinase (78.5 ± 1.53 to 82.34 ± 1.25% clot lysis). Methanolic extract also showed good activity against Gram-positive strains of bacteria, and the highest activity was observed against Bacillus subtilis. The findings of this study will improve our knowledge of phytochemistry, and biological activities of P. candollei, which seems to be a ray of hope to design formulations of natural products for the improvement of health and prevention of chronic diseases; however, further research may address the development of novel drugs for use in pharmaceuticals.