Antimicrobial photodynamic therapy and photodynamic inactivation, or killing bugs with dyes and light--a symposium-in-print

In antimicrobial photodynamic therapy, the photosensitizer (PS) in its ground singlet state absorbs light to give the excited singlet state that can transition to the long-lived triplet state. This PS triplet may undergo energy transfer (Type 2) or electron transfer (Type 1) to oxygen to form reactive oxygen species (singlet oxygen and/or hydroxyl radicals) that can kill both Gram-positive and Gram-negative bacteria and fungi. Infections in animal models can also be treated.     

Umbelliferone Decorated Water-soluble Zinc(II) Phthalocyanines – In Vitro Phototoxic Antimicrobial Anti-cancer Agents

In this contribution we report on the synthesis, characterization and application of water-soluble zinc(II) phthalocyanines, which are decorated with four or eight umbelliferone moieties for photodynamic therapy (PDT). These compounds are linked peripherally to zinc(II) phthalocyanine by a triethylene glycol linker attached to pyridines, leading to cationic pyridinium units, able to increase the water solubility of the system. Beside their photophysical properties they were analyzed concerning their cellular distribution in human hepatocyte carcinoma (HepG2) cells as well as their phototoxicity towards HepG2 cells, Gram-positive (S. aureus strain 3150/12 and B. subtilis strain DB104) and Gram-negative bacteria (E. coli strain UTI89 and E. coli strain Nissle 1917). At low light doses and concentrations, they exhibit superb antimicrobial activity against Gram-positive bacteria as well as anti-tumor activity against HepG2. They are even capable to inactivate Gram-negative bacteria, whereas the dark toxicity remains low. These unique water-soluble compounds can be regarded as all-in-one type photosensitizers with broad applications ranges in the future.     

Polarographic and Voltammetric Behavior of Complex of Pefloxacin with Manganese

Pefloxacin(PEFX) is an antibacterial agent of the fluoroquinolone group with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and has been widely used in clinical therapy. Many papers are reported that the reduction in antimicrobial activity and the decrease in bioavailability of pefloxacin with antiacids and other drugs, that has been attributed to the complex of fluoroquinolone with metal ions commonly found in antiacids and vitamin preparations.     

Photodynamic therapy: A special emphasis on nanocarrier-mediated delivery of photosensitizers in antimicrobial therapy

Resistance to antimicrobial drugs is an impending healthcare problem of growing significance. In the post-antibiotic era, there is a huge push to develop new tools for effectively treating bacterial infections. Photodynamic therapy involves the use of a photosensitizer that is activated by the use of light of an appropriate wavelength in the presence of oxygen. This results in the generation of singlet oxygen molecules that can kill the target cells, including cancerous cells and microbial cells. Photodynamic therapy is shown to be effective against parasites, viruses, algae, and bacteria. To achieve high antimicrobial activity, a sufficient concentration of photosensitizer should enter the microbial cells. Generally, photosensitizers tend to aggregate in aqueous environments resulting in the weakening of photochemical activity and lowering their uptake into cells. Nanocarrier systems are shown to be efficient in targeting photosensitizers into microbial cells and improve their therapeutic efficiency by enhancing the internalization of photosensitizers into microbial cells. This review aims to highlight the basic principles of photodynamic therapy with a special emphasis on the use of nanosystems in delivering photosensitizers for improving antimicrobial photodynamic therapy.     

Antimicrobial C-glucoside from aerial parts of Diospyros nigra

A new C-alkylglucoside, diospyrodin [beta-1C-(1'S*,2'R*,3'R*,4'S*-1',2',3',4',5'-pentahydroxypentyl)-glucopyranoside] (1) has been isolated as its nonaacetate from the leaves and stems of Diospyros nigra. Its structure was elucidated on the basis of chemical and spectral properties and a single crystal X-ray analysis. It showed antimicrobial activity against Gram-positive and Gram-negative bacteria.     

A Highly Efficient Aggregation-induced Emission Photosensitizer for Photodynamic Combat of Multidrug-resistant Bacteria

With the antibiotic abuse and the resulting increased antibiotic resistance,the bacterial infection has posed a serious threat to human health.Photodynamic therapy is an effective tool for treating localized and superficial infections.It is a promising approach for the treatment of superbugs and with minimal risk of induced antibiotic resistance.Herein,an isoquinolinium-based photosensitizer,LIQ-TPE,with aggregation-induced emission properties is designed and synthesized.It is with high 1O2 generation efficiency and shows efficient antibacterial performance towards both Gram-negative and Gram-positive bacteria,and even methicillin-resistant Staphylococcus aureus(MRSA).LIQ-TPE thus shows great promise as an effective antimicrobial agent to combat the menace of multi-drug resistant bacteria.     

Chemical composition and antibacterial activity of selected essential oils and some of their main compounds

The chemical composition of essential oils of cabreuva (Myrocarpus fastigiatus Allemao, Fabaceae) from Brazil, cedarwood (Juniperus ashei, Cupressaceae) from Texas, Juniper berries (Juniperus communis L., Cupressaceae) and myrrh (Commiphora myrrha (Nees) Engl., Burseraceae) were analyzed using GC/FID and GC/MS. The antimicrobial activity of these essential oils and some of their main compounds were tested against eleven different strains of Gram-positive and Gram-negative bacteria by using agar diffusion and agar serial dilution methods. Animal and plant pathogens, food poisoning and spoilage bacteria were selected. The volatile oils exhibited considerable inhibitory effects against all tested organisms, except Pseudomonas, using both test methods. Higher activity was observed against Gram-positive strains in comparison with Gram-negative bacteria. Cabreuva oil from Brazil showed similar results, but in comparison with the other oils tested, only when higher concentrations of oil were used.     

Cationic fullerenes are effective and selective antimicrobial photosensitizers

Fullerenes are soccer ball-shaped molecules composed of carbon atoms, and, when derivatized with functional groups, they become soluble and can act as photosensitizers. Antimicrobial photodynamic therapy combines a nontoxic photosensitizer with harmless visible light to generate reactive oxygen species that kill microbial cells. We have compared the antimicrobial activity of six functionalized C(60) compounds with one, two, or three hydrophilic or cationic groups in combination with white light against gram-positive bacteria, gram-negative bacteria, and fungi. After a 10 min incubation, the bis- and tris-cationic fullerenes were highly active in killing all tested microbes (4-6 logs) under conditions in which mammalian cells were comparatively unharmed. These compounds performed significantly better than a widely used antimicrobial photosensitizer, toluidine blue O. The high selectivity and efficacy exhibited by these photosensitizers encourage further testing for antimicrobial applications.     

Robust antimicrobial compounds and polymers derived from natural resin acids

We report novel robust resin acid-derived antimicrobial agents that exhibit excellent antimicrobial activities against a broad spectrum of bacteria (6 Gram-positive and 7 Gram-negative) with selective lysis of microbial membranes over mammalian membranes. Our results indicate that hydrophobicity and unique structures of resin acids can be determining factors in dictating the antimicrobial activity.     

A novel class of 1,4-disubstituted 1,2,3-triazoles: Regioselective synthesis,antimicrobial activity and molecular docking studies

A Novel class of 1,4-disubstituted 1,2,3-triazoles have been synthesized in good to excellent yields via Cu(I) accelerated azide-alkyne click chemistry reaction strategy. The newly synthesized compounds were assessed for their in vitro antimicrobial activity against five Gram-positive, seven Gram-negative bacteria and three fungi. Most of the synthesized compounds displayed significant activity against the tested Gram-positive and Gram-negative bacteria. Molecular docking study revealed that all docked compounds are bound efficiently with the active site of Topoisomerase IV (4EMV) receptor with the observed the free energy of binding from −7.79 to −9.44 kcal/mol. Interestingly, compound 13a forms four hydrogen bonds and displayed high binding energy (−9.44 kcal/mol) with the Topoisomerase IV (4EMV) receptor which correlated with their in vitro antimicrobial assays.     

Syntheses of antibacterial peptides,gramicidin S analogs and designed amphiphilic oligopeptides

In order to clarify the relationship between antimicrobial activity and peptide-structure, gramicidin S analogs and cationic α-helical model peptides were designed and synthesized. Introduction of cationic side chains in hydrophilic side of gramicidin S increased antimicrobial activity against Gram-negative bacteria. Amphiphilic structures of the α-helical peptides were found to be effective to show antimicrobial activities against Gram positive bacteria. Increase in number of cationic amino acid residues in the α-helical peptides caused appreciable antimicrobial activities against Gram-negative bacteria, however, induced lower activities against Gram-positive ones.     

Curcumin as a photosensitizer: From molecular structure to recent advances in antimicrobial photodynamic therapy

Nowadays multi-drug resistant microorganisms is a serious public health problem worldwide. To overcome it, new antimicrobial strategies have been developed. Among them, antimicrobial photodynamic therapy is an efficient tool against various micro-organisms in different medical and healthcare fields. The antimicrobial photodynamic protocol is based on the interaction of a photosensitizer, molecular oxygen, and an appropriate light source. Herein, we described the main physical and chemical proprieties of curcumin, an useful natural photosensitizer, including its degradation pathways, analytical methods for quantification, extraction method, synthetic methodologies, and pharmaceutical formulations used. Moreover, a comprehensive review of the past 10 years (2010−2019) concerning the application of curcumin as photosensitizer against microorganisms is described and discussed.     

Synthesis and Antimicrobial Properties of the Novel Fluonnated Bis-ammonium Salts with Two Primary Amine Groups

In order to resolve the increasing resistance phenomena of the Gram-negative bacteria against single chain quaternary ammonium salts (QAS), lysine with a pedant fluorinated bis-ammonium salts was synthesized and its antimicrobial properties were evaluated in this work. The novel fluorinated bis-ammonium salts shows similar activity with conventional single chain quaternary ammonium salts against Gram-positive bacteria but stronger activity against Gram-negative bacteria and yeast compared with the single chained counterpart.     

Chemical composition, olfactory evaluation and antimicrobial activity of selected essential oils and absolutes from Morocco

The chemical compositions of selected essential oils from North Africa, especially Morocco, of geranium, wild Moroccan chamomile and rosemary as well as absolutes of rose and geranium were determined using GC/FID and GC/MS. These oils and absolutes were tested concerning their antimicrobial activity against some food spoilage strains obtained from fresh milk and minced meat products, like sausages and pork fillet, in accordance with ISO testing procedures. Gram-positive (Bacillus cereus and Staphylococcus aureus) and Gram-negative (Escherichia coli, Salmonella abony and Pseudomonas aeruginosa) strains were used, as well as the yeast Candida albicans. Using a serial broth dilution method, all samples demonstrated weak antimicrobial activity against the Gram-negative bacteria and the yeast, compared with the activity towards the Gram-positive bacteria.     

Catecholthioether derivatives: preliminary study of in-vitro antimicrobial and antioxidant activities

In this research, synthesis, antimicrobial and antioxidant activities of a series of catecholthioethers having benzoxazole and tetrazole moieties are described. Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC) assay. The synthesized compounds were tested in vitro against three Gram-positive bacteria including Staphylococcus aureus (clinical isolated), Staphylococcus aureus ATCC 25922, Enterococcus faecium (clinical isolated), and two Gram-negative bacteria including Klebsiella pneumoniae (clinical isolated) and Pseudomonas aeruginosa 27853 and the yeast Candida albicans in comparison with control drugs. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 4-256 μg/ml. This shows compounds having tetrazole moiety were the most active against Gram-negative strains, whereas compounds having benzoxazole moiety were more active against Gram-positive ones. Also both of them showed significant antifungal activity against Candida albicans and had lower activity than the compared control drugs (Sulfamethoxazole and Fluconazole). The antioxidant activity was assessed using two methods, including, 1,1-biphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and reducing power assays. Some of the catecholthioether derivatives showed antioxidant activity more than Trolox and butylated hydroxyanisole (BHA) as reference antioxidants.     

侧链带有脂肪族双季铵盐的赖氨酸的合成及抗菌性能分析

为了解决单季铵盐扩链剂所合成的聚氨酯对革兰氏阴性细菌不敏感的问题,文中合成了侧链带有脂肪族双季铵盐的赖氨酸作为聚氨酯的扩链剂(ED8)。用质谱、核磁共振对所合成的产物进行分析。最后,通过采用最低抑菌浓度(MIC)法对ED8进行抗菌性能测试发现,ED8对革兰氏阴性细菌的抗菌效果比单季铵盐扩链剂好8倍。     

Antimicrobial properties of some bis(iminoacenaphthene (BIAN)-supported N-heterocyclic carbene complexes of silver and gold

The AgCl, AgOAc, AuCl, and AuOAc complexes of the new bis(imino)acenaphthene(BIAN)-supported N-heterocyclic carbene ligand and the precursor imidazolium salt have been investigated with respect to their antimicrobial activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Psudomonas aeruginosa. The most active antimicrobial is the precursor imidazolium salt, which has a minimum inhibitory concentration (MIC) value of <40 μg/mL. The MIC values for the silver complexes IPr(BIAN)AgCl and IPr(BIAN)AgOAc against Gram-positive S. aureus are comparable to that for AgNO?, while those against Gram-negative E. coli and P.aeroginosa are significantly larger. Similar behavior was evident for the gold acetate complex IPr(BIAN)AuOAc. However, in the case of the gold chloride analogue, the MIC values are virtually identical for both the Gram-positive and the Gram-negative bacteria.     

Composition and antimicrobial activity of the essential oil of Actinidia macrosperma from China

Actinidia macrosperma is a medicinal plant in China and has been well known for its attraction to cats and activities against leprosy and cancers. The compositions and the antimicrobial activity of its leaf oil were reported for the first time. The oil obtained by hydrodistillation and analyzed by GC and GC-MS, was characterized by the high content of monoterpenes. Linalool (48.14%) is the major component identified, followed by 1,2-dimethyl-lindoline (7.94%), linolenic acid methylester (6.57%) and (E)-phytol (5.29%). The antimicrobial activity of the oil was evaluated against four bacterial and three fungal species. The results showed that it exhibited a mild antibacterial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), a significant activity against Gram-negative bacteria (Escherichia coli), and no activity on Pseudomonas aeruginosa. The test fungi were more sensitive to the oil, with a MIC range of 0.78-1.56 microL mL(-1) than bacteria in the range which were significantly higher from 0.78 to 25.50 microL mL(-1).     

Antimicrobial activity of three baccharis species used in the traditional medicine of Northern Chile

The antimicrobial activities of aqueous ethanol and chloroform extracts of three Baccharis species currently used in Northern Chile folk medicine for the treatment of several infectious and inflammatory disorders were tested against Gram-positive and negative bacteria and fungal spp. using the agar-disc diffusion assay. The results indicated that the activity was more pronounced against Gram-positive than against Gram-negative bacteria and yeast. No significant differences on the antibacterial activity were observed in the aqueous ethanol versus chloroform extracts. None of the plant extracts evaluated exhibited any activity against ten fungi tested.     

A Supramolecular-Based Dual-Wavelength Phototherapeutic Agent with Broad-Spectrum Antimicrobial Activity Against Drug-Resistant Bacteria

With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self-assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one-dimensional wire-like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual-modal properties with significant reactive-oxygen-species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram-positive, Gram-negative, and drug-resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual-modal antimicrobial agents that are able to overcome antibiotic resistance.