Current Bioactive Compounds - Volume 15, Issue 5, 2019

Background: Thymol is a natural phenolic monoterpenoid widely used in pharmaceutical and food preservative applications. Thymol isomeric with carvacrol, extracted primarily from Thymus species (Trachyspermum ammi) and other plants sources such as Baccharisgrise bachii and Centipeda minima, has ethnopharmacological characteristics. Methods: This review was prepared by analyzing articles published on thymol moiety in last decade and selected from Science Direct, Scopus, Pub Med, Web of Science and SciFinder. The selected articles are classified and gives brief introduction about thymol and its isolation, illustrates its natural as well as synthetic sources, and also therapeutic benefits of thymol worldwide Results: Thymol has been covering different endeavors such as antimicrobial, antioxidant, antiinflammatory, antibacterial, antifungal, antidiarrhoeal, anthelmintic, analgesic, digestive, abortifacient, antihypertensive, spermicidal, depigmenting, antileishmanial, anticholinesterase, insecticidal and many others. This phenolic compound is among the essential scaffolds for medicinal chemists to synthesize more bio-active molecules by further derivatization of the thymol moiety. Conclusion: Thymol is an interesting scaffold due to its different activities and derivatization of thymol is proved to enhance its biological activities. However, more robust, randomised, controlled clinical trials would be desirable with well-characterised thymol preparations to corroborate its beneficial effects in diseased patients. Moreover, in view of the potential use of thymol and thymol-rich essential oils in the treatment of human infections, comprehensive studies on chronic and acute toxicity and also teratogenicity are to be recommended.

Background: Heterocyclic compounds containing nitrogen atoms such as pyrazoles have a long history and applicability in the field of medicinal chemistry. Many compounds containing pyrazole moiety have been reported in the available literature for their prominent biological activities, including antimicrobial activity against different microorganisms. Over the years, there has been a concern with the many health problems associated with the dramatic increase of microbial infections and resistance to standard drugs, so there is a need for the development of more effective antimicrobial agents. Pyrazoles and their derivatives are promising candidates to bypass these problems with good safety profiles, and there is a wide range of synthetic methodologies for their obtainment. This review aims to compact a literature survey (2012-2017) very informative and helpful for researchers who wish to study or continue the development of new, potent and broad-spectrum antimicrobial compounds. Methods: This review encompasses reports on the synthesis and antimicrobial evaluation of synthetic pyrazoles from the year 2012 to 2017, which were extracted from bibliographic databases such as PubMed, scielo, sciencedirect, scifinder, and scopus. The main keywords in our search were “pyrazole” and “antimicrobial activity”, in which we made efforts to include synthetic and biological methodologies that can be useful for laboratories of different levels of infrastructure. Moreover, inclusion/ exclusion criteria was applied to select quality reports which could demonstrate different tools of antimicrobial evaluation, focusing on the advances made in the area, such as evaluation in silico and exploration of the possible mechanism of action for active compounds. Results: Thirty-four papers were included in this work, which was displayed chronologically from the year 2012 to 2017 in order to enhance the advances made in the area, with at least five reports from each year. We found that the most commonly tested bacterial strains are Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and from the year 2016 onwards Mycobacterium tuberculosis. The most common tested fungal strains are Candida albicans, Aspergillus flavus, and Aspergillus niger. The majority of articles expressed the antimicrobial results as a zone of inhibition, leading to the determination of the Minimum Inhibitory Concentration (MIC) and a probable mechanism of action for the most prominent compounds, considering cytotoxicity. Aromatic aldehydes and ketones are key reactants to obtain important precursors for the synthesis of pyrazoles, such as chalcones, together with alkyl or phenylhydrazines and thiosemicarbazide. A great variation in the reported MICs was found as there is no standard maximum limit, but many compounds exhibited antimicrobial activity comparable or better than standard drugs, from which 10 reports active compounds with MIC lower than 5 μg mL-1. Conclusion: The findings of this work support the importance of pyrazole moiety in the structure of antimicrobial compounds and the versatility of synthetic methodologies to obtain the target products. Results clearly indicate that they are attractive target compounds for new antimicrobial drugs development. We hope that this information will guide further studies on continuing the search for more effective, highly active antimicrobial agents.

Anthocyanins are flavonoid compounds imparting pink, red, blue, and purple colors to fruits, flowers, leaves, and some underground organs. These pigments play an important role in pollination and fruit and seed dispersal and they are related to the protection of plant tissues exposed to biotic and/or abiotic stress. Their consumption has been linked to diverse health benefits such as anti-inflammatory and anti-carcinogenic properties, diminution of cardiovascular disease incidence, obesity control, and diabetes mitigation effects. Also, in vitro studies have revealed certain potential cancer chemopreventive activities of anthocyanins. Reactive oxygen species scavenging as well as metal chelating and direct binding to proteins have been associated with anthocyanin health effects. Recent studies have indicated that these compounds can modulate decisive signaling pathways and gene regulation. Their action contributes to vascular homeostasis and to angiogenesis, inflammation, and platelet aggregation control. Likewise, anthocyanins have been associated with the prevention of a peroxynitrite-mediated disorder in endothelial cells. The potential use of anthocyanins as colorants in food has been extensively analyzed since they are the main hydrosoluble plant pigments. However, their instability and the influence of concentration, pH, temperature, and the presence of other compounds (phenolic acids, metals) on color properties can limit anthocyanin use as food ingredients and additives. Encapsulation has been proposed as an alternative to reduce food-processing damage and to deliver these compounds to their target site in the human body. Likewise, chemical lipophilization of anthocyanins has been assayed to obtain modified compounds with higher lipophilicity, more suitable for lipid-rich matrices.

Background: The marine world is highly diversified and is of great importance for its sustainable utilization as resources for human life. Although marine resource economy has its own share in the international market, there is only a handful of research occurring, the probability of not being completely explored. It has now become virtually possible to characterize the metabolites by bioanalytical techniques and molecular biology methodology. The marine biomes harbour largely diatoms, bacteria, fungi, actinomycetes, and cyanobacteria that are harnessed for their rich structurally diverse secondary metabolites. Recently, sponges and algae have gained commercial importance. Focuses are now shifting towards ascomycota, actinobacteria, cyanobacteria and other classes due to the advanced technology in extraction of the active components from these phyla and deeper exploration of the oceans. Method: A vast report on marine natural products have been regularly updated and published which clearly indicates the immense research undertaken in ocean flora and fauna. Herein we focus on providing information on the potential uses of marine natural products as bioactive agents in the last five years. The data were collected from research and review articles from peer-reviewed journals. Results: A total of 128 articles are citied in the present review covering broad spectrum of marine organism and their importance in the field of medical biology. Information on source organisms, collection sites, was assembled and a total of 120 biologically important compounds are described here. Conclusion: The present study provides information to bioprospecting efforts in the field of marine science. Herein, I have emphasized diverse biological activities isolated from marine microbes to invertebrate against many pathogenic microorganisms and cancer, thus making marine-derived natural products valuable commodities. Future prospects for the discovery of new marine products and process development could add to the economic importance.

Background: The importance of polyphenols to curb lifestyle related disorders has also raised the worth of green tea polycatechins. Besides, optimization of extraction conditions is gaining wide acceptance to attain maximum polyphenols out of plant matrix. Methods: Considering the fact, in the present study, nine green tea solvent extracts were prepared by optimizing solvents; aqueous ethanol, aqueous acetone and aqueous ethyl acetate in 1:1 ratio and extraction time; 35, 50 & 65 min at constant temperature 50ºC to achieve an optimal quantity of green tea polycatechins. Results: The results indicated significant impact of extraction solvents and time on phytochemistry and free radical scavenging potential with maximum potential attained by acetone extracts of green tea at 50 min i.e. total polyphenols 1325.81±64.85 mg GAE/100g, flavonoids 139.78±5.42 mg/100g, DPPH (1,1- diphenyl-2-picrylhydrazyl) inhibition 86.69±4.01%, β-carotene & linoleic acid assay 78.47±3.57%, FRAP (Ferric Reducing Antioxidant Power) value 19.36±0.94 mM/L Fe+2, ABTS [2, 2'-azino-bis(3- ethylbenzothiazoline-6-sulphonic acid)] value 11.10±0.49 μM Trolox Eq/g and metal chelating activity 16.93±0.81 mg EDTA/g. Conclusion: Conclusively, acetone as solvent and 50 min extraction time have proven optimized extraction conditions for green tea polycatechins.

Background: Epilepsy is a disease of the central nervous system that affects approximately 50 million individuals worldwide. Although several new drugs have been marketed in the last 25 years, almost one-third of patients are not protected. In many cases, currently available drugs produce undesirable side effects. As a result, a need exists for novel anticonvulsants with unique mechanisms of action and minimal side effects. Methods: A mixed anhydride coupling procedure and standard deprotection procedures were utilized to prepare 36 α-amino acid amides. All final products were evaluated in mice and rats utilizing a standard battery of anticonvulsant tests. Results: α-Amino acids containing a 2,6-dimethylanilide group exhibited anticonvulsant activity in the maximal electroshock seizure test and 6 Hz test in mice and rats. A small, branched-chain on the α- carbon generally maintained or enhanced anticonvulsant activity in the maximal electroshock seizure test. The (R)-α-amino acid amides were typically more potent and slightly more neurotoxic than the corresponding (S)-enantiomers. The valine dimethylanilide (R)-42 was highly active in the MES test in mice (ED50 = 3.6mg/kg) and rats (ED50 = 3.8 mg/kg). (R)-42 also demonstrated excellent anticonvulsant activity in the 6 Hz, picrotoxin, and corneal kindled mouse tests. Furthermore, (R)-42 did not lower seizure threshold when evaluated in the intravenous metrazol seizure test. Conclusion: α-Amino acid 2,6-dimethylanilides exhibited potent activity in a variety of anticonvulsant tests in mice and rats. The valine derivative (R)-42 represents a promising compound for potential use in complex partial seizures.

Background: Burn injuries are the most common injuries and a major health problem affecting communities worldwide. Many alternative therapies are used as treatment for burns. The healing efficacy of sulphated polysaccharide ascophyllan was evaluated and studied its mechanism of action on experimental burn wounds in rats. Methods: Ascophyllan fractions were extracted from marine brown algae Padina tetrastromatica (Dictyotaceae) and evaluated its burn wound healing potential. Full thickness burn wounds induced in male albino rats were used for in vivo study and evaluated wound healing parameters. Results: The results showed that Ascophyllan Fraction 3 (AF3) had no cytotoxic effect and it increases cell migration and production of VEGF in fibroblasts. AF3 significantly reduced in vitro secretion of cytokines in blood mononuclear cells treated with Lipopolysaccharide (LPS). In vivo study showed that AF3 (5%) has significant wound healing activity in albino rats and this dose was used for studying the healing mechanism. The reference control used for the study was povidone-iodine ointment. Wound area contraction and reepithelialisation was faster in AF3 (5%) administered group. When applied topically, AF3 (5%) increased hydroxyproline and hexosamine content at the wound site. Uronic acid, DNA and proteins levels were also increased. Compared to the control groups, AF3 (5%) treatment showed an increase in neovascularization and fibroblast proliferation as evidenced by histopathology of granulation tissue. Conclusion: Sulphated polysaccharide ascophyllan is beneficial for the wound environment as it enhances the healing process and suggested the safe usage of this algal polysaccharide as an alternative for replacing current synthetic wound healing agents in medicine.

Background: Epilepsy is one of the most prevalent noncommunicable neurological conditions. More than 10 million people in India are afflicted with epilepsy. Treatment available has many detrimental side effects. Up to one-third of epilepsy patients remain resistance to optimum drug treatment. These facts triggered the further scope and search for newer more effective and less toxic anticonvulsants. Methods: Quinazolinone semicarbazone derivatives showing protection in chemoconvulsant induced seizure models (as reported in our previous study) were further screened in MES and scPTZ induced seizure models. Neurotoxicity was determined; quantification of anticonvulsant activity and toxicity was also done. Finally compounds were screened by liver functional test to ascertain the possible hepatotoxicity in the active compounds. Results: Compounds N-1- (menthone) -N- {[3-(4-(substituted)-phenyl) -4-oxo- 3,4-dihydroquinazolin- 2-yl] methyl} semicarbazone (3A-d-4, 3B-d-4 and 3C-d-4) showed significant protection in both MES and scPTZ induced seizure model with no neurotoxicity at the given dose. In MES test, compounds showed an ED50 close to that of phenytoin and carbamazepine. They also showed Protective Index (PI) higher as compared to phenytoin and carbamazepine. A high safety profile (HD50/ED50 values) was noted and hypnosis, analgesia, and anesthesia were only observed at higher doses. Conclusion: Compounds showed no significant increase or decrease in the concentration of alkaline phosphatase, Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), albumin and bilirubin.

Background: Substituted pyrimidine derivatives (non-nucleoside) are found to be associated with various biological activities. The various substituted pyrimidines are also having significant in vitro activity against different DNA and RNA viruses. The present study focuses on the anti-PV activity of new pyrimidines and their condensed derivatives. Methods: A series of novel pyrimidines and their condensed derivatives were synthesized and their structures were confirmed by spectral data. Their antiviral activities against poliovirus type 3 (PV-3) were evaluated in vitro. In cell culture, morphological changes observed in cells infected with polioviruses, including cell rounding and detachment from the substrate, are generally termed cytopathic effects (CPE). The effects of synthetic pyrimidines on PV amplification in a culture of the heteroploid cell line, Vero 76 (African green monkey kidney cells) were investigated. Results: Bioassays in vitro showed that one of seven synthesized compounds, 7-(Benzenesulfonyl)-5- benzyl-N-(prop-2-en-1-yl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine, has potent antiviral activity against PV-3 (EC50 = 0.75 μM). The selectivity index of this compound is similar to that of pirodavir. Conclusion: The need for antiviral agents to treat PV-associated diseases remains great, but few options currently exist. Here we show that substituted pyrimidine derivatives are a promising structure class of chemical compounds for the development of antiviral drugs against PV infections.

Background: Outbreaks of foodborne diseases cause substantial economic losses. Universities, research institutes and the food industry are increasing their efforts to enhance food safety worldwide. In this context, the study of essential oils as natural antimicrobials and antioxidants for use in foods has become increasingly important. Methods: The volatile composition and antioxidant and antibacterial activity of Pelargonium graveolens, Cymbopogon citratus, Citrus bergamia, Rosmarinus officinalis and Mentha piperita essential oils were evaluated. Results: The essential oils showed 80.5 to 95.0% of monoterpenes, but with different profiles. The free radical scavenging activity by the DPPH assay ranged from 3.53 to 68.55% and the total antioxidant potential measured by FRAP ranged from 1.28 to 94.61 mmol TE g-1. The antioxidant activity (FRAP and DPPH assays) of the essential oils followed the order: C. citratus > M. piperita > P. graveolens > C. bergamia > R. officinalis. In general, when the pH tended to neutrality a higher concentration of essential oil was needed to inactivate the microorganisms. The C. citratus oil presented interesting results regarding the inhibition of both strains of S. aureus, showing a lower MIC50 value and Minimum Bactericidal Concentration (MBC) in the concentrations evaluated for E. coli and S. enterica. Conclusion: The results suggest that C. citratus essential oil has potential as an antibacterial and antioxidant agent.