Active Antimicrobial Agents Research Articles

Immobilizing hydrolytic active Papain on biodegradable PLLA for biofilm inhibition in cardiovascular applications

Abstract The use of biomaterials in medicine is becoming increasingly important. One of the main concerns is the foreign body associated infection caused by direct microbial contamination or clinical infections. The bacterial biofilm formation on biomaterials depends on their surface properties. Therefore, several anti-adhesive surface modifications were developed. Nevertheless, the demand for antimicrobial agents that prevent bacterial colonisation is still largely unmet. The immobilization of active antimicrobial agents, such as antibacterial peptides or enzymes, offers a potential approach to achieve long-lasting effectiveness. In this investigation, the hydrolytic enzyme papain with its published antibacterial activity was covalently immobilized on the well-established biodegradable biomaterial poly-L-lactic acid (PLLA). For the characterization of the enzymes on the PLLA surfaces, the protein content and enzyme activity were determined. A biofilm assay was performed to test the effect of the papain-modified PLLA samples on the biofilm-forming bacterial strain Clostridioides difficile, one of the most frequently occurring human nosocomial pathogens. The investigated hydrolytic enzyme papain could be immobilized by coupling via the crosslinker EDC to the PLLA surface. Detection was performed by determination of the amount of protein and the reduced biofilm growth after 24 h and 72 h compared to the reference.

Antibiotic Sensitivity Pattern of Clinical Isolates of Pseudomonas aeruginosa at a Tertiary Care Hospital in Saudi Arabia

Among gram-negative microorganisms Pseudomonas aeruginosa is the most common bacteria identified in different clinical specimens of hospitalized patients. A few studies have been conducted in Saudi Arabia regarding antibiotic susceptibility pattern. The purpose of this study was to evaluate the current levels of antibiotic susceptibility and to assess the resistance pattern of antibiotics among the clinical isolates of P. aeruginosa in the King Khalid Hospital, Alkharj, Kingdom of Saudi Arabia. This study was carried out during January, 2015 to May, 2015. A total of 180 different specimens such as sputum, urine, pus swabs, wound swabs etc. were collected from different patients admitted to the hospital. Thirty (30) clinical isolates of P. aeruginosa were isolated from different specimens of the patients suspected of having respiratory tract infection, urinary tract infection, wound infections, etc. The antibiotic susceptibility profiles of all the isolates were determined using Kirby-Bauer disk diffusion method. Piperacillin-tazobactam was found to be the most active antimicrobial agent with 96.7% susceptibility followed by cefepime (83.3%), ceftazidime (83.3%), and ciprofloxacin (76.7%). All isolates were resistant to ertapenem, cefuroxime, cefoxitin and nitrofurantoin. Anti-bacterial treatment strategies should focus on P. aeruginosa, for which the prevalence rates are increasing every year. The usage of piperacillin-tazobactam, cefepime, ceftazidime and ciprofloxacin must be reserved and only be given to the patients after susceptibility test to reduce the resistance of P. aeruginosa against these agents.
 Dhaka Univ. J. Pharm. Sci. 19(1): 77-82, 2020 (June

Preparation of some novel thiazolidinones, imidazolinones, and azetidinone bearing pyridine and pyrimidine moieties with antimicrobial activity

AbstractBy aiming to design new antimicrobial agents, we prepared new series of thiazolidin‐4‐ones(12a–d), imidazolin‐4‐ones(13a–d), and azetidin‐2‐ones (14a–d), having pyridine and pyrimidine moieties. Chemical structures of these derivatives were elucidated by the use of spectral and elemental analyses. All the new substituted pyridopyrimidines were subjected to in vitro antimicrobial testing by estimating the zone of inhibition toward Bacillus subtilis and Staphylococcus aureus, as examples of bacterial species, in addition to Aspergillus flavus and Candida albicans, as examples of fungal species. The results of antimicrobial testing detected that all the screened derivatives displayed antibacterial effect; especially azetidin‐2‐one derivative, (14c), was the most active one. Regarding the antifungal potential, only thiazolidinone derivatives, 12a and 12c, and the imidazolinone, 13c, displayed inhibitory activity toward Aspergillus flavus, while all the tested compounds, 12a–d, 13a–d, and 14a–d, except 14a, produced inhibitory potential toward Candida albicans. Docking studies of the most active antimicrobial agents, 12c, 13c, and 14c, within GLN‐6‐P, recorded good scores with several binding interactions with the active site.

Recent Studies on the Antimicrobial Activity of Transition Metal Complexes of Groups 6–12

Antimicrobial resistance is an increasingly serious threat to global public health that requires innovative solutions to counteract new resistance mechanisms emerging and spreading globally in infectious pathogens. Classic organic antibiotics are rapidly exhausting the structural variations available for an effective antimicrobial drug and new compounds emerging from the industrial pharmaceutical pipeline will likely have a short-term and limited impact before the pathogens can adapt. Inorganic and organometallic complexes offer the opportunity to discover and develop new active antimicrobial agents by exploiting their wide range of three-dimensional geometries and virtually infinite design possibilities that can affect their substitution kinetics, charge, lipophilicity, biological targets and modes of action. This review describes recent studies on the antimicrobial activity of transition metal complexes of groups 6–12. It focuses on the effectiveness of the metal complexes in relation to the rich structural chemical variations of the same. The aim is to provide a short vade mecum for the readers interested in the subject that can complement other reviews.

Aztreonam for Neisseria gonorrhoeae: a systematic review and meta-analysis.

Ceftriaxone is the only consistently active antimicrobial agent recommended for the treatment of Neisseria gonorrhoeae. Although some new antimicrobials are in development, the necessity to expand treatment options in the near term may require using older drugs that have not been widely used to treat gonorrhoea. We conducted a literature review of clinical trials and case series, published from 1983 to 2017, reporting treatment efficacy results following administration of 1 g aztreonam intramuscularly or IV for uncomplicated gonococcal infections. We summed trial data, stratified by anatomical site of infection, and calculated summary efficacy estimates and 95% CI for each site of infection. The 10 identified clinical trials enrolled 678, 38 and 16 individuals with urogenital, rectal and pharyngeal gonorrhoea, respectively. Aztreonam had an efficacy of 98.6% (95% CI: 97.5%-99.4%) for urogenital, 94.7% (95% CI: 82.3%-99.4%) for rectal and 81.3% (95% CI: 54.4%-96.0%) for pharyngeal gonococcal infections. Although most clinical trials included in this meta-analysis were conducted >30 years ago, aztreonam appears to have excellent efficacy for urogenital gonorrhoea; its efficacy at extragenital sites remains uncertain.

Novel Benzimidazole Acetamide Derivatives as Antibacterial and Anti-Tubercular Agents: Synthesis and Characterization

The current study focused on the development of novel potentially active anti-microbial agents based on the benzimidazole-acetamide system. A novel series of various substituted benzimidazole- N- phenyl acetamides was synthesized through a feasible scheme characterized by IR, Proton nuclear magnetic resonance (1 HNMR), and MASS spectral methods. All the synthesized compounds were screened for antibacterial activity against two gram-positive strains: Staphylococcus aureus, Bacillus subtilis; four gramnegative strains: Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, and Klebsiella pneumonia; and anti-tubercular activity against mycobacterial strain: Mycobacterium tuberculosis. Among the 15 compounds (6a–6o) tested, three compounds, 6e, 6f, 6l, and 6m demonstrated high potency with MIC values ranging from 6.25–12.5μg/mL against both gram-positive and gram-negative strains. In addition, compounds 6e, 6f, and 6l displayed the highest anti-tubercular activity with a MIC value of 25μg/mL.

One System for All: Is Mass Spectrometry a Future Alternative for Conventional Antibiotic Susceptibility Testing?

The two main pillars of clinical microbiological diagnostics are the identification of potentially pathogenic microorganisms from patient samples and the testing for antibiotic susceptibility (AST) to allow efficient treatment with active antimicrobial agents. While routine microbial species identification is increasingly performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), routine AST still largely relies on conventional and molecular techniques such as broth microdilution or disk and gradient diffusion tests, PCR and automated variants thereof. However, shortly after the introduction of MALDI-TOF MS based routine identification, first attempts to perform AST on the same instruments were reported. Today, a number of different approaches to perform AST with MALDI-TOF MS and other MS techniques have been proposed, some restricted to particular microbial taxa and resistance mechanisms while others being more generic. Further, while some of the methods are in a stage of proof of principles, others are already commercialized. In this review we discuss the different principal approaches of mass spectrometry based AST and evaluate the advantages and disadvantages compared to conventional and molecular techniques. At present, the possibility that MS will soon become a routine tool for AST seems unlikely – still, the same was true for routine microbial identification a mere 15 years ago.

519. Multidrug-resistant Gram-Negative Bacteremia in Pediatric Patients: Is It Time to Change to Empiric Meropenem?

BackgroundThe rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients.MethodsAll episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results.ResultsA total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1.ConclusionIn our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.

Effect of biodegradable polymeric film "Biodept-DF" on biological tightness and physical strength of postoperative suture of the stomach in experiment

Objective. Assessment of the effect of the new biodegradable polymer film "Biodep-DF" developed by us on the biological tightness and physical strength of the postoperative wound of the stomach in the experiment.Material and methods. The study was carried out on 50 guinea-pigs, observing all the requirements of humane treatment of the experimental animals. Animals were divided into groups, operated on the stomach and examined on the physical strength of the stomach scar by pneumocompression and biological tightness by studying the microflora in the scar region.Results. The stiffness of the stomach was higher in the group of animals, where films with decamethoxin and hydrated fullerene C60 were applied. This is especially true at the 3rd and 7th days of the study. Samples taken during the research and microbiological researches showed the absence of pathogenic flora in the area of the scar and surrounding tissues in all terms of observation.Conclusions. The biodegradable polymer film "Biodep DF", thanks to its active protective and antimicrobial agents, increases the strength of the postoperative scar of the stomach in the early postoperative period and provides the biological sealing of the seam after surgical intervention.

First Example of Cationic Cyclopentadienyliron Based Chromene Complexes and Polymers: Synthesis, Characterization, and Biological Applications

The present work encompasses development of a new class of active antimicrobial agents of the ɳ6-arene-ɳ5-cyclopentadienyliron (II) complexes and polymers to expand the existing family of antimicrobials. The design of the first example of these cationic organoiron complexes, incorporating chromene moieties, was successfully accomplished in good yield via the Steglich esterification, followed by the nucleophilic aromatic substitution reactions to isolate their polymeric analogues. Meanwhile, the structural identities of the new materials were confirmed using 1H and 13C NMR, IR, and elemental analysis. The molecular weight of the new polymeric materials was estimated using viscosity measurements, and was found to be in the range of 10,000 and 31,000. The chromene-containing organoiron complexes displayed reversible reduction behaviors as their functionalized polymers. Meanwhile, the TGA thermogram revealed initial weight losses due to the cleavage of the cationic iron moieties, while the second weight losses were dependent upon the etheric linkages in the polymer backbones. This study, therefore, focuses on the exploration of the antimicrobial and antitumor performance of the new materials along with their structure activity relationship.

Antibacterial, antibiofilm and molecular modeling study of some antitumor thiazole based chalcones as a new class of DHFR inhibitors

Some synthesized antitumor derivatives of thiazole based chalcones including thiazolo[2,3-b]quinazoline and pyrido[4,3-d]thiazolo[3,2-a]pyrimidine analogues were subjected to be tested against standard microbial strains. Compound 18 showed higher activity against both Gram-positive and Gram-negative bacteria with MIC of 1.0, 1.0, 2.0, 2.0 and 4.0 μg/ml against S. aureus, B. subtilis, M. luteus, E. coli and P. aeuroginosa respectively which is better than ampicillin and very relative to ciprofloxacin standards. Moreover, this compound shows a good anti-biofilm activity against the Gram positive bacteria. Molecular docking studies of synthesized compounds against DHFR enzyme were carried out. Interestingly, active anticancer candidates 22,38, 40 and 41 in addition to most active antimicrobial agents 15, 18 and 20 bind to DHFR with nearly the same amino acid residues as MTX especially mentioning Arg28, Arg70, Asn64 and Lys68 which support our hypothesis that these compounds could act as antitumor or antibacterial via DHFR inhibition. Flexible alignment and surface mapping techniques have further provided lipophilic distributions supporting effective binding to DHFR. ADMET calculations for compounds 15, 18 and 20 suggested that they could be good orally absorbed antibacterial agents while compound 38 could be an orally absorbed anticancer agent with diminished toxicity. The results highlight studied thiazole based chalcones as efficient leads for designing new future antibacterial drug candidates.

Synthesis and anti-microbial activities of azomethine and aminomethyl phenol derivatives

A series of azomethine and aminomethyl phenol derivatives has been synthesized and characterized by mass, IR, and NMR spectral techniques.In vitro antimicrobial activities of all these compounds were evaluated against different gram-positive and gram-negative bacterial and fungal strains by measuring zone of inhibition using agar diffusion method. Results of antimicrobial screening indicated that the compound 4a was the most active antimicrobial agent (100 µg/mL). The compounds 3a, 4e, 4f were exhibited best in vitro anti-microbial activity against the gram positive bacterial strains such as Bacillus subtilis, Micrococcus luteus and gram negativebacterialstrain Salmonella typhi andfungalstrain Candida albicans.

PREVALENCE OF BLATEM, BLASHV, AND BLACTX-M GENES AMONG ESBL-PRODUCING KLEBSIELLA PNEUMONIAE AND ESCHERICHIA COLI ISOLATED FROM THALASSEMIA IN ERBIL, IRAQ

BackgroundDue to the recent appearance of organisms that are resistant to several drugs (multidrug-resistant) like Enterobacteriaceae that produce extended-spectrum β-lactamase (ESBL, concerns have remarkably increased regarding the suitable treatment of infections. The present study was an investigation into ESBL molecular characteristics among clinical isolates of Klebsiella pneumoniae and Escherichia coli resulting in urinary tract infections (UTIs) and their pattern of antimicrobial resistance in order to come up with helpful information on the epidemiology of these infections and risk factors accompanied with them.MethodsIn order to conduct the study, 20 K. pneumoniae and 48 E. coli were isolated and retrieved from thalassemia center in Erbil, Iraq during July 2016 and September 2016. The collected strains were analyzed and the profile of their antimicrobial susceptibility was specified. In order to spot β-lactamase genes (i.e. blaTEM, blaSHV, and blaCTX-M), polymerase chain reaction was conducted.ResultsThe findings obtained from multiplex PCR assay showed that out of the collected strains of ESBL-producing E. coli, had 81% blaTEM, 16.2% blaSHV, and 32.4% blaCTX-M genes. Similarly, 64.7% blaTEM, 35.2% blaSHV, and 41.1% blaCTX-M genes existed in the isolates of K. pneumoniae. It was found that antibiotic resistance pattern of E. coli and K. pneumoniae isolates to 20 antibiotics varied widely. It was also concluded that the majority of the K. pneumoniae and E. coli isolates were multi-drug resistant (MDR). Moreover, 75% and 87.5% of respectively K. pneumoniae and E. coli isolates showed the MDR phenotypes.ConclusionTEM prevalence was high among other types of ESBLs. Over all, the most active antimicrobial agents in vitro remained to be the carbapenems.

Encapsulation of coriander essential oil in cyclodextrin nanosponges: A new strategy to promote its use in controlled-release active packaging

In this work, we exploit the antimicrobial properties of coriander essential oil (CEO) incorporated in dextrin-derived nanosponges to create a stable controlled release system. Nanosponges (CD-NS) were loaded with CEO, characterized by means of scanning and transmission electron microscopy (SEM and TEM) and X-ray diffraction (XRD), and tested for their antimicrobial activity against foodborne pathogens. A head-space-solid phase microextraction coupled to gas chromatography (HS-SPME-GC–MS) method to assess CEO five major compounds was successfully validated. CEO loading was dependent on solvent and CD-NS choice. Additionally, CEO incorporation in CD-NS increased its crystallinity. While β-CD-NS and HP-β-CD:β-CD-NS incorporated higher CEO amounts than α-NS, the later proved more effective regarding their antimicrobial activity. CEO-α-CD-NS and CEO-HP-β-CD:β-CD-NS revealed a predominant bactericidal activity, CEO-β-CD-NS only exhibited a bacteriostatic action. We describe, for the first time, the incorporation of whole EOs in CD-NS and their ability to provide a controlled oil release, especially in the cases of β-derived-CD-NS, while inhibiting bacterial growth, creating a potential new strategy to overcome the poor efficacy of current antimicrobial food packaging. The manufacturing of antimicrobial food packages is still hindered by the problems posed by its lack of efficiency and poor compound stability. The fact that the cyclodextrin nanosponges synthetized in this work can provide a controlled release of antimicrobial active agent, in this case, coriander essential oil while preserving this compound's antimicrobial activity against foodborne pathogens can open the doors for its use in antimicrobial food packaging films. Furthermore, given that cyclodextrin nanosponges are stable at temperatures over 200 °C, gives the packaging industry the opportunity of incorporating this technology during the extrusion process of film making, making the process of active packaging materials cheaper, faster and more readily scalable. • HP-β: β-CD-NS encapsulated the highest amount of CEO (60 μg/mg NS). • A HS-SPME-GC/MS method was validated to quantify CEO five major compounds. • NS yielded a controlled CEO release dependent on culture medium and temperature. • α-NS and HP-β: β-CD had a predominant bactericidal action on foodborne bacteria. • NS-released CEO was effective at concentrations lower than the MIC for free CEO.

Screening for antifungal activity of garlic (Allium sativum) powder against mycelia growth of three post-harvest pathogens

Screening for antifungal activity of garlic powder against mycelia growth of three post-harvest pathogens (Aspergillus, Rhizopus and Mucor species) was investigated in this study. Five grams of malt extract agar (MEA) were poured into a conical flask, 100 ml of water and different weight of garlic powder (1, 3, 5 and 7 g) were separately added, stirred and later sterilized while MEA medium with no garlic added (0 g) served as control. The mycelia of each post-harvest pathogen was cut with 6mm cork borer and placed on the solidified medium in the Petri dish and incubated at 28±2oC for 72 hours. Phytochemical screening of the garlic powder was also investigated. Results from this study showed that the different weights of the garlic powder apart from the control (0 g garlic) significantly inhibited the mycelia growth of the three post-harvest pathogens tested in the study and the order of antifungal activity of the garlic powder against mycelia growth of Aspergillus, Rhizopus and Mucor species was 7 g > 5 g > 3 g > 1 g > 0 g, 5 g > 7 g >1 g > 3 g > 0 g and 7 g > 5 g > 3 g > 1 g > 0 g respectively. The antifungal activity of the garlic powder may be related to the presence of active antimicrobial agents including alkaloids, saponins, tannins, flavonoids and cardiac glycosides that were detected in the powder. DOI: http://dx.doi.org/10.5281/zenodo.2635824

Quaternary ammonium surfactants derived from leucine and methionine: Novel challenging surface active molecules with antimicrobial activity

Surfactants are versatile excipients, which are commonly employed in several pharmaceutical formulations as emulsifiers, stabilizing or solubilizing agents. In this field, current research is aimed at the design or discovery of amphiphilic molecules with improved characteristics in terms of safety (toxicological profile) and biological activities (e.g. antimicrobial activity, interaction with biomembranes). Quaternary ammonium surfactants derived from amino acids are one such class of compounds with significant potential for pharmaceuticals. In this work, quaternary ammonium surfactants derived from the amino acids leucine and methionine and esterified with fatty acids of different lengths (C10, C12 and C14) were synthesized. These amphiphiles were characterized in terms of critical micelle concentration (CMC) by tensiometry and conductivity measurements, cytotoxicity (MTS and LDH assay on Caco-2 and Calu-3 cell lines) and antimicrobial activity on selected Gram-positive (S. aureus and E. faecalis), Gram-negative (E. coli and P. aeruginosa) and the fungus C. albicans. The derivatives bearing a C12 or a C14 chain displayed CMC, EC50 (from cytotoxicity assays) and minimum inhibition concentration (MIC) values that are comparable to those of benzalkonium chloride (used as reference), especially towards Gram-positive and C. albicans. On the contrary, derivatives bearing a C10 chain have higher CMC, EC50 and MIC values, highlighting the crucial role of the hydrophobic tail in determining both physicochemical and biological properties. The C12-C14 synthesized derivatives may represent a promising alternative to benzalkonium chloride as surface active molecules and antimicrobial agents.

Morpholine Based Diazenyl Chalcones: Synthesis, Antimicrobial Screening and Cytotoxicity Study.

Microbial infections have been the major cause of morbidity and mortality for the centuries and continue to present the formidable challenge to the human health. Several studies have been performed to explore the antimicrobial potential of various synthesized chalcone derivatives. The morpholine derivatives are also gaining considerable importance due to diverse biological activities. Hybridization of morpholine and chalcone moiety together can be the useful approach for the development of new effective antimicrobial agents. A new series of morpholine based heterocyclic diazenyl chalcones (MD1-MD21) was synthesized, characterized and evaluated for antimicrobial potential by tube dilution and agar diffusion methods. The most active derivatives were also evaluated for cytotoxicity towards mouse fibroblast cell line (L929) and the human lung cancer cell line (A549) and for haemolysis to check the toxicity on human red blood cells. MD-6 was found highly active against different microbial strains, particularly S. typhi, E. coli, A. niger and C. albicans having the MIC in the range of 1.95 µg/ml to 3.91 µg/ml. MD-9 and MD-21 were also found to have good antimicrobial activity. The most active diazenyl derivatives exhibited very low cytotoxicity towards L929 cell line (IC50 ranges from 360 µg/ml - 902.3 µg/ml) and A549 cell line (IC50 ranges from 35.42 µg/ml - 216.4 µg/ml) as compared to the standard drug 5-FU (IC50 ranges from 1 µg/ml - 2 μg/ml) against these cell lines. The active derivatives showed haemolysis of 10-15% up to 150 µg/ml concentration. MD-6, MD-9 and MD-21 were found to be most active antimicrobial agents. These derivatives demonstrated high safety profile by exhibiting very low cytotoxicity and also revealed their safety for human blood cells with haemolysis of 0.2-5.5% at their antimicrobial concentration.

Synthesis of Sulfonated Dihydrofuropyrazoles Derivatives as Antimicrobial Active Agents

A series of sulfonyl dihydrofuropyrazole derivatives was prepared from one pot multi component condensation of sulfonated β-keto ester, aromatic aldehyde, hydrazine, pyridinium ylide in presence of piperidine catalyst under ethanol solvent conditions and subsequent oxidation of SPh group with MCPBA. All the synthesized compounds were characterized by analytical and spectral techniques and screened in vitro for antimicrobial activity. The activity data revealed that most of the compounds exhibited good to significant activities. Compounds 6b, 6i, 6j, 6k, 6m, 6n exhibited good and broad spectrum activity towards all the tested bacterial strains.

Nanoclays in Food and Beverage Packaging

In this study, we present and discuss the technical benefits of using nanoclays as a promising property enhancer in organic polymers for food and beverage packaging. The incorporation of nanoclays can improve the thermal, mechanical, and barrier properties of a host polymer. Both natural hydrophilic and modified organophilic nanoclays provide unique characteristics to the host polymer depending on the selected applications. Besides the advantage of polymer reinforcement, various novel applications of nanoclays in food packaging have been suggested recently, such as control and release for active ingredients, antimicrobial agent, and carrier for the colorimetric indicator system. The existing migration studies discussing the transition from plastic to nanoclay packaging revealed that the diffused level of aluminum and silicon in the nanoclay packaging are within the limitation proposed in Council Directive 90/128/EEC (1990). Therefore, until now, there is no safety restriction in the use of clay nanocomposite films in food packaging applications.

Recent Highlights on the Synthesis of Pyrazoles with Antimicrobial Activity

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.