Current Bioactive Compounds - Volume 14, Issue 1, 2018

Background: Living organisms are a natural source of β-amino acids and peptides containing them. Many marine organisms and plants are able to produce by themselves such compounds, e.g. depsi-peptides and macrocyclic molecules, which possess different biological activities, mostly concerned to the treatment of human diseases. Methods: Literature has been collected ranging from 1980 until now; both reviews and research articles have been carefully considered and cited in our paper. Results: Literature revealed an increased interest in natural bioactive peptides incorporating β-amino acids. Several papers focused their attention on structural characteristics of depsipeptides and cyclic compounds incorporating them in marine organisms, which may influence and determine the specific biological activity in vivo. Conclusion: In this brief review, we collect a series of naturally occurring peptides incorporating β- amino acids, with the aim to update the arsenal of bioactive compounds available, highlighting the significant structural modifications which are the base of the exerting biological properties.

Background: The oxadiazine insecticides are broad-spectrum insecticides with a novel mode of action by blocking insect neuronal sodium channels. Indoxacarb is an oxadiazine insecticide to reduce cross-resistance. A series of tricyclic oxadiazine analogues were designed and synthesized in order to find novel active compounds with high bioactivities similar to that of the commercial insecticide indoxacarb. Methods: We undertook the modification of the N-aryl group of indoxacarb with various aromatic groups, including substituted benzene, naphthalene and pyridine rings. Forty-one oxadiazine analogues were synthesized, and characterized by NMR spectroscopy and elemental analysis. The insecticidal activities of the newly synthesized compounds against Nilaparvata lugens, Mythimna separata, Tetranychus cinnabarinus and Aphis medicaginis were tested. Results: The results of bioassays indicated that among all the synthesized compounds tested, eight compounds (27, 33, 35, 36, 37, 38, 39 and 40) showed 100% insecticidal activities against Mythimna separata at the concentration of 500 mg/L. Compound 17 and 25 showed 80% insecticidal activities against Mythimna separata at the concentration of 500 mg/L. Compound 6 showed 78% insecticidal activity against Aphis medicaginis at the concentration of 500mg/L. Further investigation revealed that compound 39 showed excellent insecticidal activity with an EC50 of 4.59 mg/L against Mythimna separata. Conclusion: The data suggested the following general trend of bioactivities for the substituted N-aryl groups: benzene > substituted pyridine > substituted naphthalene. The bioactivities rendered by substituted groups on the aryl rings followed the general trend of OCF3 > SCF3 > CF3> I > Br > Cl > NO2 > acyloxyl > alkoxy and hydroxyl. Among these eight active compounds, compound 39 showed to be the most potent. The insecticidal activity of compound 39 is only slightly weaker than that of indoxacarb. Compound 39 should have the potential to be developed into a novel potential insecticide with a more desirable activity profile.

Background: Passion fruit is known to be rich in flavonoids and can be an important antioxidant, preventing the oxidative damage. The objective of this study was first to evaluate the antioxidant activity of Passiflora alata fruit extract in the liver of Wistar rats and second to compare the efficacy of pretreatment or co-treatment of this extract. Method: Antioxidant activity of Passiflora alata fruit extract was analyzed by lipid peroxidation (TBARS), protein oxidation (carbonyl), Sulfhydryl levels and enzymatic activity of superoxide dismutase (SOD) and of catalase (CAT) against sodium azide damage induced in the liver of Wistar rats. Results: The pre-treatment extract reduced and/or prevented the lipid peroxidation and protein oxidative damage caused by sodium azide. The co-treatment didn't show any protection at the level of protein oxidation damage, in this case an increase of damage was observed. Sulfhydryl levels increased in all groups. The SOD activity was not significantly different between groups, but the CAT activity increased in the group with co-treatment. Conclusion: Pre-treatment with passion fruit (Passiflora alata) can be an alternative in reducing oxidative damage in the liver.

Background: In the present study, a series of substituted phenyl β,β-diphenylpropanoate were synthesized by the reaction of β,β-diphenylpropionyl chloride with various substituted phenols in acetone. Methods: Upon synthesis of compounds, the characterization of synthesized compounds was made using IR, NMR, Mass spectroscopy and elemental anaysis. These derivatives were screened for analgesic activity and anti-inflammatory activity (Carrageen induced paw edema method) Diclofenac sodium and Indomethacin were used as standard drug for analgesic activity and anti-inflammatory response, respectively. Results: The compounds 2-nitro Phenyl 3,3 diphenyl propionate (HD-5) and 4-nitro Phenyl 3,3 diphenyl propionate (HD-2) exhibited significantlly potent anti-inflammatory and analgesic activity (two to three times) when comparision was made with control group. The response of promising compound (HD-5) for analgesic and anti-inflammatory action was highest among all the test compound and was almost similar to the standard compounds (Indomethacin and Diclofenac Sodium). Conclusion: The findings of present work confirm the potent action of HD-5 compounds as analgesic and anti-pyretic in experimental animals.

Background: Prazequantel (Prz) is an important medication in humans and animals. It acts against a number of pathogens. In this study, Prz nanoemulsion (PrzNE) was prepared and evaluated for toxic, cytotoxic and mutagenic potentials. Materials and Methods: The cytotoxic effect of PrzNE was observed in Artemia salina and Allium cepa, while toxicity and mutegenicity in A. cepa test system. Potassium di-chromate (K2Cr2O7) and copper sulphate (CuSO4.5H2O) were taken as standards for A. salina and A. cepa test, respectively. Results: PrzNE at 16 μM caused 100% mortality of the brine shripms. It exerted a concentrationdependent toxic and cytotoxic effects in A. cepa and A. salina. In comparison to the CuSO4.5H2O, PrzNE produced less chromosomal aberrations (CA), where chromosomal fragments/loose and bridges were most frequently observed. Conclusion: PrzNE may readily cross the cell membranes of A. cepa and A. salina, increase the permeability of the cell membrane and/or exert an oxidative stress, thus causes a cytotoxic effect. The PrzNE was more cytotoxic than mutagenic in nature.

Background: Chalcones holding arylic substitutions and pyrazolic chalcones were reported as potent antimicrobial and antioxidant agents. Prompted by the literature, it was considered of interest in the present work to develop the bioactive materials incorporating five, and six-membered ring heterocycles in a single molecular framework with above molecules. Methods: Synthesis of chalcone derivatives derived from condensation of 2-(3,5-dimethyl-pyrazol-1- yl)-1-phenyl-ethanone and aldehydes has been discussed. Sodium hydride was employed as catalyst to facilitate the reaction which proved to be a worthy catalyst over NaOH and KOH. This protocol offers advantages such as easy workup, shorter reaction time and promising yield for the synthesis of chalcones. Further, another aromatic ring was installed to the chalcones to obtain pyrimidine, isoxazole, and pyrazole derivatives. The structures of the prepared compounds were confirmed by FT-IR, 1H NMR, 13CNMR spectroscopy, Mass spectrometry and elemental analysis. The biological activity of the compounds against four bacterial strains namely Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and three fungal strains have been evaluated. Results: An improved process for biologically useful chalcone derivatives has been discussed providing overall good yield. The newly synthesized compounds were screened for in vitro antioxidant and antimicrobial activity. Based on the preliminary results, compounds 5c, 6c, 6d in this series showed significant activity against tested bacterial strains. Compounds 6b, 6c, 6d and 7b showed potent inhibitory activity against fungal growth. Among them, compound 6c displayed the most potent activity against Candida parapsilosis, Candida tropicalis, Candida albicans, which was comparable with standard drug fluconazole. Conclusion: Synthesis, characterization and biological evaluation of new heterocyclic pyrazole chalcones has been described. The method of preparation of these compounds is very straightforward and free of tedious work up as well quite time saving. All the compounds have shown moderate to good inhibitory activity against B. subtilis and exhibited mild to moderate antibacterial activities against the other tested organisms.

Background: Praziquantel (Prz)-induced membrane permeability causes cell death of organisms. It may have antioxidative/pro-oxidative capacity. The aim of this study was to prepare Prz nanoemulsion and evaluate antioxidant capacity. Materials and Methods: Radical scavenging capacity was checked by 1,1-dipheny-picrylhydrazyl (DPPH), azino-bisethylbenzthiazoline-sulfonic acid (ABTS); hydroxyl (OH) and nitrite oxide (NO) radical assays, while lipid peroxidation was done by thiobarbitiric acid substances (TBARS), reduction potential (RP) by ferric reduction, and membrane protection by hemolysis (HL) inhibition test in rat erythrocytes taking Trolox (TRO), an α-tocopherol analogue as a positive control. Additionally, an oxidative/antioxidative potential of PrzNE was checked in a wild type (SOD-WT) and deficient (SOD1Δ, SOD2Δ, CAT1Δ, SOD1ΔSOD2Δ and SOD1ΔCAT1Δ) Saccharomyces cerevisiae strains using hydrogen peroxide (H2O2) as a stressor. Results: PrzNE, in a concentration-dependent manner, scavenged free radicals. It significantly (p <0.05) scavenged NO and OH radicals. PrzNE, alone induced slight oxidative stress, while in cotreatment, it significantly (p <0.05) protected S. cerevisiae strains from the damaging effect of H2O2. Conclusion: The OH and NO radical scavenging capacity may be linked to the protective effect of the RBCs membrane and S. cerevisiae cells. PrzNE exerted a moderate antioxidative capacity.

Background: A variety of methods have been reported for the synthesis of pyrano[2,3- d]pyrimidines in the literature. Many of these methods are associated with some limitations and generally need expensive or non-available reagents, prolonged reaction times and high temperatures. Thus, the introduction of new methods and /or further work on technical improvements to overcome these limitations is still needed. Pyrano[2,3-d]pyrimidines were prepared by condensation reaction of aldehyde, malononitrile and barbituric acid or 2-thiobarbituric acid by a new efficient procedure and antibacterial activity of selected products was evaluated. Methods: A mixture of barbituric acid or thiobarbituric acid (2 mmol) aldehyde (2 mmol), and malononitrile (2 mmol)) in the presence of poly (4-vinylpyridine) (0.10 g) was refluxed in H2O:EtOH H2O:EtOH under normal and ultrasonic irradiation conditions for appropriate time. After cooling, the resulting precipitate was filtered, and the crude product was purified by recrystalization from EtOH:H2O to obtain a pure product. Antibacterial activity of products was evaluated using Staphylococcus aureus, Bacillus cereus, Pseudomonasn aeruginosa, and Escherichia coli bacteria strains. Results: 2,4-Dioxo-1H-pyrano[2,3-d]pyrimidine and 4-oxo-2-thioxo-1H-pyrano[2,3-d]pyrimidine derivatives were synthesized under the optimized conditions. In all cases, the reactions proceeded efficiently at reflux temperature in H2O:EtOH to afford the corresponding products. All the products were characterized by mp. IR, 1H- and 13C-NMR spectra. Antibacterial activity of selected synthesized pyrano[2,3- d]pyrimidines was tested against gram-positive and gram-negative bacteria strains. The verification of antibacterial screening data revealed that the selected compounds have bactericidal properties against Staphylococcus aureus, Bacillus cereus, Pseudomonasn aeruginosa, and Escherichia coli bacteria strains. Conclusion: We have developed an efficient procedure for the synthesis of pyrano[2,3-d]pyrimidine derivatives via three-component condensation of aromatic aldehydes, malononitrile and barbituric acid or thiobarbituric acid in two different reaction conditions in the presence of catalytic amount of a cheap and readily available catalyst poly (4-vinylpiridine). The bacterial activity study revealed that two compounds showed moderate to good antibacterial activities.

Background: Several Serratula species are used in folk medicine and showed interesting biological activities. The objective of this work was to continue the investigation of the chemical composition of the ethyl acetate extract of the flowers of Serratula cichoracea which in our previous study showed a significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) essay compared to quercetin used as control molecule and to evaluate the isolated compounds for their antioxidant and antimicrobial activities. Methods: Ethyl acetate extract (15 g) was fractionated by column chromatography on silica gel. After purification on preparative plates, the isolated compounds were identified by spectral analyses mainly high resolution electrospray ionisation mass spectrometry (HR-ESIMS) and one- and two-dimensionnal nuclear magnetic resonance spectroscopy experiments, and were evaluated in vitro for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl radical and for antimicrobial properties. Results: A new phytoecdysteroid named 22-epi-ajugasterone C (1) together with ajugasterone C (2), were isolated. Compounds 1 and 2 had weak scavenging effect compared with myricetin used as positive control, whereas the two compounds showed antimicrobial properties against multiresistant strains like Staphylococcus aureus, Escherichia coli, Serratia sp., Klebsiella pneumoniae and Candida albicans. Conclusion: The new isolated phytoecdysteroid and its epimer ajugasterone C, responded to their effectiveness against different various antibiotic-resistant bacteria.

Background: 2-phenylethylamine (2-PEA) is an organic neurotransmitter which belongs to a class of biogenic amines that are essential for regulation of cellular development, differentiation and homeostasis. This class of compounds have been reported to cause oxidative stress to neuronal cells in the brain, which have a high oxygen consumption rate, elevated iron content and low antioxidant concentration. 2-phenylethylamine can metabolise into hydroxyl radicals which have been found to be a direct cause of oxidative stress within cells. Methods: This study has examined the toxicity of 2-phenylethylamine in the yeasts, Saccharomyces cerevisiae and Candida glabrata by examining growth with glucose or ethanol as sources, in the presence of 2-phenylethylamine. Results: 2-phenylethylamine was found to be inhibitory to all strains of yeast where respiratory function was necessary, while growth where glucose was the carbon source was unaffected. Almost all growth inhibition could be reversed by antioxidants ascorbate and glutathione, indicating oxidative stress was the likely cause of toxicity through 2-PEA or one of its metabolites. Conclusion: Yeast studies show that the biogenic amine, 2-phenylethylamine, targets respiratory function and that the inhibition can be reversed alleviated by the addition of glutathione or ascorbate.

Background: According to the Indian traditional system of medicine, Paederia foetida L. (Rubiaceae) is considered as the most valuable drug for numerous protective effects against different types of metabolic diseases and disorders such as inflammation, arthritis, pain, etc. To date, no study has been undertaken to scrutinize the systemic and topical anti-inflammatory effect of Paederia Foetida L. The present study is an attempt to scrutinize systemic and topical anti-inflammatory effect of Paederia foetida L and its possible mechanism of action. Materials and Methods: In vitro antioxidant studies were performed via hydrogen peroxide (H2O2), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), nitric acid (NO) and superoxide model for free radical scavenging potential. Oral and topical anti-inflammatory activity of Paederia foetida L. methanolic extract was experimented through carrageenan, egg albumin, serotonin, histamine, xylene, Arachidonic acid (AA) and 12-O-tetradecanoylphorbol-acetate (TPA) established methods. Result & Discussion: PF extract confirmed the presence of total phenolic phytoconstituents in the PF extract. Invitro antioxidant studies confirmed that the PF extract scavenges the free radical in various models. On the other hand, PF extract significantly reduces the carrageenan-induced inflammation by inhibiting the synthesis of prostaglandin (PGE2); egg-induced inflammation via reduction in secretion of serotonin and histamine. Topical inflammation induced by the xylene, TPA and AA, was subsided significantly (P<0.001) by the PF extract in a dose-dependent manner via inhibition of PGE2, 5- lipooxygenae and cyclo-oxygenase. Conclusion: We can now conclude that PF extract inhibits the systemic and topical inflammation in dosedependent manner. The PF extract probably inhibited the synthesis of PGE2, 5-lipooxygenae and cyclooxygenase.

Background: Salvia species contain bioactive secondary metabolites and possess several pharmacological activities. The objective of this study was to determine the chemical composition and antimicrobial activity of essential oil from the aerial parts of Salvia pachystachys. Methods: The essential oil was obtained by means of hydrodistillation and its components were analyzed using gas chromatography and mass spectrometry (GC/MS). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the oil were determined against standard microbial strains; Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. Results: Thirty-six compounds were identified in the oil. The major volatile components were camphor (31.0%), 1,8-cineol (13.5%), camphene (11.7%) and α-pinene (8.0%). Oxygenated monoterpenes predominated in the S. pachystachys oil, and constituted 50.7% of the total oil composition. The values of MIC and MBC for the most sensitive strain, Staph. aureus, were 1.25 and 5.0 mg/mL, respectively, and for the most resistant strain, Pseudomonas aeruginosa and E. coli, were 5.0 mg/mL. Using bioautography assay, five compounds (camphor, 1,8-cineol, borneol, spathulenol and caryophellene oxide) were found to be responsible for the observed antimicrobial activity of the oil against S. aureus. Conclusion: These results indicated that the essential oil of S. pachystachys has moderate antimicrobial activity.

Background: Alzheimer disease is a neurological disease related to age which is characteristic of excess of oxidative stress and deficit level of acetylcholine in the brain. Centella asiatica (Linn.) have several beneficial pharmacological activities such as antioxidant, anti-inflammatory and memory enhancing activities. Objective: To evaluate the phenolic contents, antioxidant and AChE inhibitory activities of different fractions of Centella asiatica grown in Vietnam. Methods: The leaves of Centella asiatica were extracted with ethanol 96% and fractionated with nhexane, ethyl acetate and butanol solvents. These fractions were investigated the antioxidant activity by DPPH assay and acetylcholinesterase (AChE) inhibitory activity by Ellman's colorimetric method. Results: Our results showed that the total phenolic content of BuOH fraction was the highest, being equivalent to 68.4 ± 2.4 mg quercetin/g of fraction. Our data also demonstrated that BuOH fraction had the strongest antioxidant activity with IC50 of 7.76 ± 0.74 μg/mL and AChE inhibitory activity with an IC50 value of 36.31 ± 2.45 μg/mL in a concentration-dependent manner, followed by EtOAc fraction and nhexane fraction with the weakest activity. Kinetic inhibition analysis indicated BuOH fraction of mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) of 34.36 ± 2.34 μg/mL. Conclusion: Our data suggest that the BuOH fraction of Centella asiatica may be a promising source of AChE inhibitors for Alzheimer's disease.

Brackground: In our previous study, we have shown that the ethanol, chloroform and nhexane extracts of Dysophylla auricularia revealed antimicrobial, anti-diarrheal, anti-inflammatory and membrane stabilization, alpha-glycosidase inhibitory and antipyretic activities. This study aims to evaluate the antioxidant capacity of methanol extract of D. auricularia (MDA) using some non-clinical test systems. Materials and Methods: The methanol hot extract of the herb was undergone for six in vitro and one ex vivo and one in vivo antioxidant assays. An alpha-tocopherol analogue, trolox (6-hydroxy-2,5,7,8- tetramethylchroman-2-carboxylic acid) was taken as a standard for in vitro and ex vivo tests, while hydrogen peroxide (H2O2) as a stressor for in vivo assay. Results: The results suggest MDA within 12.5 to 500 μg/ml exhibited prominent radical scavenging, reduction potential, and inhibition of hemolysis capacities. Additionally, MDA dose-dependently exhibited an antioxidative defense against H2O2 induced damage in Saccharomyces cerevisiae (in vivo) test strains. Conclusion: D. auricularia may be one of the potential sources of antioxidant compounds.