Antibacterial Natural Products Research Articles

Integrative Genomics and Bioactivity-Guided Isolation of Novel Antimicrobial Compounds from Streptomyces sp. KN37 in Agricultural Applications.

Actinomycetes have long been recognized as an important source of antibacterial natural products. In recent years, actinomycetes in extreme environments have become one of the main research directions. Streptomyces sp. KN37 was isolated from the cold region of Kanas in Xinjiang. It demonstrated potent antimicrobial activity, but the primary active compounds remained unclear. Therefore, we aimed to combine genomics with traditional isolation methods to obtain bioactive compounds from the strain KN37. Whole-genome sequencing and KEGG enrichment analysis indicated that KN37 possesses the potential for synthesizing secondary metabolites, and 41 biosynthetic gene clusters were predicted, some of which showed high similarity to known gene clusters responsible for the biosynthesis of antimicrobial antibiotics. The traditional isolation methods and activity-guided fractionation were employed to isolate and purify seven compounds with strong bioactivity from the fermentation broth of the strain KN37. These compounds were identified as 4-(Diethylamino)salicylaldehyde (1), 4-Nitrosodiphenylamine (2), N-(2,4-Dimethylphenyl)formamide (3), 4-Nitrocatechol (4), Methylsuccinic acid (5), Phenyllactic acid (6) and 5,6-Dimethylbenzimidazole (7). Moreover, 4-(Diethylamino)salicylaldehyde exhibited the most potent inhibitory effect against Rhizoctonia solani, with an EC50 value of 14.487 mg/L, while 4-Nitrosodiphenylamine showed great antibacterial activity against Erwinia amylovora, with an EC50 value of 5.715 mg/L. This study successfully isolated several highly active antimicrobial compounds from the metabolites of the strain KN37, which could contribute as scaffolds for subsequent chemical synthesis. On the other hand, the newly predicted antibiotic-like substances have not yet been isolated, but they still hold significant research value. They are instructive in the study of active natural product biosynthetic pathways, activation of silent gene clusters, and engineering bacteria construction.

Antibacterial Marinopyrroles and Pseudilins Act as Protonophores.

Elucidating the mechanism of action (MoA) of antibacterial natural products is crucial to evaluating their potential as novel antibiotics. Marinopyrroles, pentachloropseudilin, and pentabromopseudilin are densely halogenated, hybrid pyrrole-phenol natural products with potent activity against Gram-positive bacterial pathogens like Staphylococcus aureus. However, the exact way they exert this antibacterial activity has not been established. In this study, we explore their structure-activity relationship, determine their spatial location in bacterial cells, and investigate their MoA. We show that the natural products share a common MoA based on membrane depolarization and dissipation of the proton motive force (PMF) that is essential for cell viability. The compounds show potent protonophore activity but do not appear to destroy the integrity of the cytoplasmic membrane via the formation of larger pores or interfere with the stability of the peptidoglycan sacculus. Thus, our current model for the antibacterial MoA of marinopyrrole, pentachloropseudilin, and pentabromopseudilin stipulates that the acidic compounds insert into the membrane and transport protons inside the cell. This MoA may explain many of the deleterious biological effects in mammalian cells, plants, phytoplankton, viruses, and protozoans that have been reported for these compounds.

Jugiones A-D: Antibacterial Xanthone-Anthraquinone Heterodimers from Australian Soil-Derived Penicillium shearii CMB-STF067.

The Australian roadside soil-derived fungus Penicillium shearii CMB-STF067 was prioritized for chemical investigation based on an SDA cultivation extract exhibiting both antibacterial properties and natural products with unprecedented molecular formulae (GNPS). Subsequent miniaturized 24-well plate cultivation profiling (MATRIX) identified red rice as optimal for the production of the target chemistry, with scaled-up cultivation, extraction and fractionation yielding four new xanthone-anthraquinone heterodimers, jugiones A-D (1-4), whose structures were assigned by detailed spectroscopic analysis and biosynthetic considerations. Of note, where 1-2 and 4 were active against the Gram-positive bacteria vancomycin-resistant Enterococcus faecalis (IC50 2.6-3.9 μM) and multiple-drug-resistant clinical isolates of Staphylococcus aureus (IC50 1.8-6.4 μM), and inactive against the Gram-negative bacteria Escherichia coli (IC50 > 30 μM), the closely related analog 3 exhibited no antibacterial properties (IC50 > 30 μM). Furthermore, where 1 was cytotoxic to human carcinoma (IC50 9.0-9.8 μM) and fungal (IC50 4.1 μM) cells, 2 and 4 displayed no such cytotoxicity (IC50 > 30 μM), revealing an informative structure activity relationship (SAR). We also extended the SAR study to other known compounds of this heterodimer class, which showed that the modification of ring G can reduce or eliminate the cytotoxicity while retaining the antibacterial activity.

Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery.

Often referred to as the "second genome", the human microbiome is at the epicenter of complex inter-habitat biochemical networks like the "gut-brain axis", which has emerged as a significant determinant of cognition, overall health and well-being, as well as resistance to antibiotics and susceptibility to diseases. As part of a broader understanding of the nexus between the human microbiome, diseases and microbial interactions, whether encoded secondary metabolites (natural products) play crucial signalling roles has been the subject of intense scrutiny in the recent past. A major focus of these activities involves harvesting the genomic potential of the human microbiome via bioinformatics guided genome mining and culturomics. Through these efforts, an impressive number of structurally intriguing antibiotics, with enhanced chemical diversity vis-à-vis conventional antibiotics have been isolated from human commensal bacteria, thereby generating considerable interest in their total synthesis and expanding their therapeutic space for drug discovery. These developments augur well for the discovery of new drugs and antibiotics, particularly in the context of challenges posed by mycobacterial resistance and emerging new diseases. The current landscape of various synthetic campaigns and drug discovery initiatives on antibacterial natural products from the human microbiome is captured in this review with an intent to stimulate further activities in this interdisciplinary arena among the new generation.

Stereoselective synthesis of thailandamide A methyl ester.

A convergent strategy for the stereoselective synthesis of the methyl ester of the structurally challenging and highly labile antibacterial polyene polyketide natural product thailandamide A has been developed. The key steps include the Zincke aldehyde reaction, Stille cross coupling, Negishi reaction, Julia-Kocienski olefination, cross metathesis, and the less explored Pd(I)-based Heck coupling to access different unsaturation bonds. Additionally, Urpi acetal aldol, Evans methylation, and Crimmins acetate aldol reactions were employed to construct four out of six asymmetric centers of the molecule.

Melanin antibacterial activity of two new strains, SN1 and SN2, of Exophiala phaeomuriformis against five human pathogens

Abstract Melanin is an almost ubiquitous pigment of brown to dark black color synthesized by living organisms. It has excellent potential for application in several fields, especially in pharmaceuticals. Yeasts are known for their ability to synthesize pigments, including melanin. These yeasts are considered black yeasts. However, there is little information on the synthesis of melanin by these yeasts. This work was designed to study the ability of black yeast to produce a diffusible dark pigment on agar. Two strains of black yeast, SN1 and SN2, were isolated from hydrocarbon-polluted soils. Based on morphological, physiological, and molecular analyses, the two strains SN1 and SN2 were identified as new species of the Exophiala phaeomuriformis strain. After pigment extraction, melanin was characterized using UV and Fourier transform infrared spectroscopy. We found that melanin synthesis is strongly affected by light and optimal parameters such as temperature 30°C, salinity between 10 and 30 ppt, and basic pH. Both melanin extracts also showed inhibitory activity against pathogenic germs, and activities were observed on E. coli (33.33 ± 2.88 mm), Pseudomonas aeruginosa (29.33 ± 4.61 mm), and Staphylococcus aureus (24.3 ± 7.65 mm). It was concluded that the melanin of the E. phaeomuriformis strain isolated from oil-polluted soils had high antibacterial activity. This high antibacterial activity could be a suitable source of new antibacterial natural products.

Inhibitors targeting BamA in gram-negative bacteria

Antibiotic resistance has led to an increase in the number of patient hospitalizations and deaths. The situation for gram-negative bacteria is especially dire as the last new class of antibiotics active against these bacteria was introduced to the clinic over 60 years ago, thus there is an immediate unmet need for new antibiotic classes able to overcome resistance. The outer membrane, a unique and essential structure in gram-negative bacteria, contains multiple potential antibacterial targets including BamA, an outer membrane protein that folds and inserts transmembrane β-barrel proteins. BamA is essential and conserved, and its outer membrane location eliminates a barrier that molecules must overcome to access this target. Recently, antibacterial small molecules, natural products, peptides, and antibodies that inhibit BamA activity have been reported, validating the druggability of this target and generating potential leads for antibiotic development. This review will describe these BamA inhibitors, highlight their key attributes, and identify challenges with this potential target.

The catechol moiety of obafluorin is essential for antibacterial activity.

Obafluorin is a Pseudomonas fluorescens antibacterial natural product that inhibits threonyl-tRNA synthetase (ThrRS). It acts as a broad-spectrum antibiotic against a range of clinically relevant pathogens and comprises a strained β-lactone ring decorated with catechol and 4-nitro-benzyl moieties. The catechol moiety is widespread in nature and its role in the coordination of ferric iron has been well-characterised in siderophores and Trojan horse antibiotics. Here we use a combination of mutasynthesis, bioassays, enzyme assays and metal binding studies to delineate the role of the catechol moiety in the bioactivity of obafluorin. We use P. fluorescens biosynthetic mutants to generate obafluorin analogues with modified catechol moieties. We demonstrate that an intact catechol is required for both antibacterial activity and inhibition of the ThrRS molecular target. Although recent work showed that the obafluorin catechol coordinates Zn2+ in the ThrRS active site, we find that obafluorin is a weak Zn2+ binder in vitro, contrasting with a strong, specific 1 : 1 interaction with Fe3+. We use bioassays with siderophore transporter mutants to probe the role of the obafluorin catechol in Fe3+-mediated uptake. Surprisingly, obafluorin does not behave as a Trojan horse antibiotic but instead exhibits increased antibacterial activity in the presence of Fe3+. We further demonstrate that Fe3+ binding prevents the hydrolytic breakdown of the β-lactone ring, revealing a hitherto unreported function for the catechol moiety in natural product bioactivity.

Synergistic Antibacterial Effect and Mechanism of Allicin and an Enterobacter cloacae Bacteriophage.

Enterobacter cloacae is a troublesome pathogen causing refractory infections of the lower respiratory tract, urethra and abdominal cavity, endocarditis, osteomyelitis, and neonatal septicemia. It is prone to developing resistance to ordinary antibiotics and has brought a serious problem to clinical treatment. An artful synergistic combination of an antibacterial natural product allicin and a newly isolated bacteriophage, named BD523, was constructed herein. This combination significantly lowered effective dosage of allicin and effectually overcame bacterial drug-resistance. We experimentally evidenced that allicin interacts with bacterial DNA in the groove region by inserting itself into the DNA double helix and, subsequently, disrupts the bacterial DNA by cleaving phosphate diester bonds of deoxynucleotides. Further, BD523 destroys the cell wall and membrane of bacteria by synthesizing lyase proteins, including holin and endolysins. Thus, the synergistic effect of the combination benefits from complementary targeting mechanisms of allicin and BD523. They cooperatively act on bacterial DNA, cell wall, and membrane to improve antibacterial efficiency and avoid drug-resistance. IMPORTANCE Bacterial drug-resistance is a serious problem afflicting pharmacologists all over the world. Many strategies have been developed and practiced to overcome it, but almost no one is satisfactory due to the continual change of bacteria. Combinations of antibiotics and bacteriophages are promising because of the cooperation of 2 bacterial killers with distinct mechanisms. The combination of allicin and an Enterobacter cloacae bacteriophage reported herein can significantly improve the effect of allicin against E. cloacae. Its synergistic effect was even superior to the combination of bacteriophage and neomycin, of which the MIC was significantly lower than allicin. It was ascribed to the complementary antibacterial and the possible resistance-proof mechanism of bacteriophage and allicin. This study provided a pragmatic way to conquer the cunning bacterium, and may offer reference for research and development of new bacterial killers.

Structure Elucidation of Antibiotics.

To date, there are hundreds of characterized natural products with antibacterial activity against pathogenic bacteria, and several have become bonafide antibiotic drugs. The development of antibacterial natural products into antibiotic drugs, both in the past and in the future, hinges upon an accurate description of the exact chemical structure of the compound. Bolstered by some form of mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy is the primary technique for elucidating the chemical structure of organic molecules including natural products. By combining various one-dimensional (1D) and two-dimensional (2D) experiments, the connectivity between atoms is established and a complete "picture" of the molecule is thereby revealed.

Anti-Salmonella activity on multidrug-resistant strains and cytotoxicity of extracts and constituents of Garcinia brevipedicellata and Garcinia epunctata

The morbidity of Salmonella infections remains high partly due to emergence of multidrug-resistant (MDR) strains. Garcinia species have demonstrated activity against a wide range of infectious organisms including bacteria. Two species, Garcinia brevipedicellata and G. epunctata were investigated for activity against MDR clinical isolates of Salmonella. Methanol extracts of the leaves of both plants were serially re-extracted using ethyl acetate (EtOAc), acetone (Ace) and methanol (MeOH); and the three extracts tested for antibacterial activity by disc diffusion and microdilution methods, and cytotoxicity effects against monkey kidney epithelial (LLCMK2) cells. Five of eighteen pure compounds isolated, identified and tested for activity include β-sitosterol (1), stigmasterol (2), epunctosides A (3), B (4) from G. epunctata and brevipedicelone D (5) from G. brevipedicellata; among which three are new compounds (3, 4 and 5). The EtOAc extract of G. epunctata and brevipedicelone D (5), recorded maximum diameters of zones of inhibition of 18 and 17 mm respectively corresponding to moderate activity. All the four crude extracts recorded the lowest minimum inhibitory concentration (MIC) of 0.125 µg/mL, corresponding to high activity against MDR Salmonella isolates and control strains. Brevipedicelone D (5) showed moderate activity with the lowest MIC of 16 µg/mL. All the crude extracts and compound 5 were not cytotoxic (CC50 = 250 - 809µg/mL). Low minimum bactericidal concentrations (≤ 2 mg/mL) were recorded against most bacteria strains which may indicate bactericidal activity. This is the first report of moderate to high activity against MDR Salmonella and no cytotoxicity of the leaves and pure compounds from G. brevipedicellata and G. epunctata; hence, the leaves should be further investigated as a potential alternative treatment for infections of these strains and source of an antibacterial natural product lead.

Drug development concerning metallo-β-lactamases in gram-negative bacteria.

β-Lactams have been a clinical focus since their emergence and indeed act as a powerful tool to combat severe bacterial infections, but their effectiveness is threatened by drug resistance in bacteria, primarily by the production of serine- and metallo-β-lactamases. Although once of less clinical relevance, metallo-β-lactamases are now increasingly threatening. The rapid dissemination of resistance mediated by metallo-β-lactamases poses an increasing challenge to public health worldwide and comprises most existing antibacterial chemotherapies. Regrettably, there have been no clinically available inhibitors of metallo-β-lactamases until now. To cope with this unique challenge, researchers are exploring multidimensional strategies to combat metallo-β-lactamases. Several studies have been conducted to develop new drug candidates or calibrate already available drugs against metallo-β-lactamases. To provide an overview of this field and inspire more researchers to explore it further, we outline some promising candidates targeting metallo-β-lactamase producers, with a focus on Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Promising candidates in this review are composed of new antibacterial drugs, non-antibacterial drugs, antimicrobial peptides, natural products, and zinc chelators, as well as their combinations with existing antibiotics. This review may provide ideas and insight for others to explore candidate metallo-β-lactamases as well as promote the improvement of existing data to obtain further convincing evidence.

Total synthesis and antibacterial evaluation of Empetroxepins A and B and related analogs

Empetroxepins A and B, which are 10,11-dihydrodibenz[b,f]oxepins produced by the Black Crowberry (Empetrum nigrum), displayed weak anti-tubercular activity upon isolation, but have not been explored for antibiotic activity despite their molecular similarity to other phenolic antibacterial natural products. Herein we detail the first total synthesis of Empetroxepins A and B via a selective demethylation strategy and antibacterial structure activity relationship (SAR) study of the natural products and related analogs. Empetroxepin A was found to be weakly active against susceptible strains of Staphylococcus aureus (SA) and Bacillus subtilis (BS) with a minimum inhibitory concentration (MIC) of 256 μg/mL against both bacteria, whereas Empetroxepin B was found to be weakly active against only BS (MIC = 256 μg/mL). Neither natural product was active against Escherichia coli (EC). Antibiotic activity was improved through derivatization of the 10,11-dihydrodibenz[b,f]oxepin core with the best compound of the SAR series, 9-chloro-10,11-dihydrodibenzo[b,f]oxepine-2,3,4-triol, having MICs of 8 μg/mL, 16 μg/mL, and 256 μg/mL against SA, BS, and EC respectively.

Bioactivity and Chemical Characterization of Sudanese Bee Honey: Crude Acacia and Its Organic Extracts.

Honey has recently been rediscovered as an antibacterial and wound-healing natural product. The medicinal properties of honey originate from the floral source used by bees. The objective of the current study was to evaluate the antimicrobial activity of Sudanese crude acacia bee honey and its solvent extracts regarding its biological activity and chemical characterization. To verify the nature of the antibacterial agent(s) of honey, sample (A) Sudanese crude unprocessed acacia bee honey obtained from west of Sudan (Nyala) during October 2019 was tested in vitro for antibacterial activity against 10 standard microorganisms Enterobacter aerogenes: ATCC: 13048, Enterococcus faecalis: ATCC: 29212, Escherichia coli: ATCC: 25922, Klebsiella pneumoniae: ATCC: 700603, Pseudomonas aeruginosa: ATCC: 27853, Serratia marcescens: ATCC: 8100, Staphylococcus aureus: ATCC: 29213, Staphylococcus epidermidis: ATCC: 12228, Staphylococcus Methicillin Sensitive MSSA: ATCC: 29213, and Staphylococcus Methicillin-Resistant MRSA: ATCC: 23591. Extraction of honey sample was carried out by petroleum ether followed by ethyl acetate using liquid/liquid extraction technique, using separating funnels. All organic extracts in addition to their aqueous residue were tested in vitro for antibacterial activity against the10 standard microorganisms. Ethyl acetate extract was subjected to gas chromatography-mass spectrometer (GC-MS) for chemical characterization. Sudanese crude unprocessed acacia honey showed inhibitory effects against the 10 standard microorganisms. Petroleum ether extract showed no antibacterial activity against the tested organisms, while its water residue exhibited remarkable activity. The ethyl acetate extract exhibited strong antibacterial activity against the tested organisms, while its aqueous residue showed no activity. Ethyl acetate extract subjected to gas chromatography-mass spectrometer (GC-MS) showed twenty-one chemical constituents. The GC-MS showed twenty-one chemical compounds, and phenolic compound was the highest concentration. Ethyl acetate extract exhibited strong antibacterial activity which can be formulated as topical dressing for wounds and burns. The usage of honey in a professional context should be taken into consideration while treating burns and wounds.

Isolation and purification of terpenoid compounds from Ferula haussknechtii and evaluation of their antibacterial effects

The roots of F. haussknechtii are used by local people in order to treat wounds and urinary infections. Ferula species are rich in bioactive compounds with biological effects. In line with our previous studies about screening antibacterial natural products, five terpenoid derivatives were purified from Ferula haussknechtii. The separation and purification were performed by column chromatography. Their structures were determined by 1 D and 2 D NMR as hawraman 8-p-hydroxybenzoyl-tovarol (1), ferutinin (2), lancerotriol 6-(p-hydroxybenzoate) (3), chimganin (4), and chimgin (5). Then, the antibacterial effects of the purified compounds were evaluated by measuring their MIC values against Gram-positive and Gram-negative bacteria. The results showed that compound (1) had the most antibacterial effect on Bacillus cereus (MIC = 16 µg/mL). The antibacterial effects of F. haussknechtii compounds are in line with their local application and it is suggested that further studies should be conducted to determine their mechanism of action.

Cyclodextrin metal–organic framework by ultrasound-assisted rapid synthesis for caffeic acid loading and antibacterial application

Cyclodextrin metal–organic framework by ultrasound-assisted rapid synthesis for caffeic acid (CA) loading and antibacterial application (U-CD-MOF) was successfully studied and this method shortened the preparation time to a few minutes. It was found that the ultrasonic power, reaction time and temperature would affect the morphology and size of the obtained crystal. Under the optimal conditions, U-CD-MOF had a cubic structure with uniform size of 8.60 ± 1.95 μm. U-CD-MOF was used to load the antibacterial natural product CA to form the composite (CA@U-CD-MOF) and the loading rate of CA@U-CD-MOF to CA could reach 19.63 ± 2.53%, which was more than twice that of γ-CD. Various techniques were applied to characterize the synthesized crystal, including Powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and N2 adsorption. In addition, antibacterial tests were performed on the obtained crystal. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CA@U-CD-MOF for Escherichia coli O157: H7 (E. coli O157: H7) were both 25 mg·mL−1, and the MIC for Staphylococcus aureus (S. aureus). was 25 mg·mL−1. The sustained release behavior of CA@U-CD-MOF to CA in ethanol fitted well to Higuchi model and the loading of CA was supported by molecular docking results. In general, U-CD-MOF was successfully achieved by ultrasound-assisted rapid synthesis and the obtained crystal was further evaluated for potential antibacterial application.

Antibacterial natural products from microbial and fungal sources: a decade of advances.

Throughout the ages the world has witnessed the outbreak of many infectious diseases. Emerging microbial diseases pose a serious threat to public health. Increasing resistance of microorganisms towards the existing drugs makes them ineffective. In fact, anti-microbial resistance is declared as one of the top public health threats by WHO. Hence, there is an urge for the discovery of novel antimicrobial drugs to combat with this challenge. Structural diversity and unique pharmacological effects make natural products a prime source of novel drugs. Staggeringly, in spite of its extensive biodiversity, a prominent portion of microorganism species remains unexplored for the identification of bioactives. Microorganisms are a predominant source of new chemical entities and there are remarkable number of antimicrobial drugs developed from it. In this review, we discuss the contributions of microorganism based natural products as effective antibacterial agents, studied during the period of 2010-2020. The review encompasses over 140 structures which are either natural products or semi-synthetic derivatives of microbial natural products. 65 of them are identified as newly discovered natural products. All the compounds discussed herein, have exhibited promising efficacy against various bacterial strains.

Cranberry and Sumac Extracts Exhibit Antibacterial and Anti-Adhesive Effects Against Streptococcus pyogenes.

Group A Streptococci (GAS) or Streptococcus pyogenes is responsible for acute bacterial pharyngitis in children as well as adults. Streptococcal pharyngitis is initiated by successful attachment and colonization of the bacteria, followed by the establishment of the biofilm in various environments. In this study, we examined the antibacterial activities of in-house prepared aqueous and ethanolic extracts of 10 Atlantic Canada fruits in the context of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill kinetics, and adhesion inhibition properties against S. pyogenes. Per our findings, MIC and MBC for all the tested extracts ranged from 0.25 to 8 mg/mL and from 4 to 64 mg/mL, respectively. Accordingly, at 1⁄2 × MBC, cranberry and sumac extracts also lowered the attachment of GAS to the uncoated and fibronectin-coated substratum. Particularly, cranberry and sumac aqueous extracts were more effective against the adhesion of S. pyogenes ATCC 19615 to the fibronectin-coated surface than a clinical strain. In conclusion, ethanolic and aqueous extracts of cranberry and sumac could potentially be incorporated into natural health products designed for the amelioration of strep throat, yet a detailed understanding of its mode of action (e.g., biofilm inhibition and eradication) could pave its path to the field of antibacterial natural health product discovery, design, and development.

A Novel Antifouling RO Polyamide/Myrrh Membrane for Waste Water Purification

In the present work, desalination of real samples from Dumat Al-Jandal Lake water (located in Jouf region) was carried out via reverse osmosis (RO) technique. The growth of bacteria on the surface of RO membrane is an essential issue of this method. It creates defects in membrane properties as salt rejection and preparation. Many approaches have been proposed to prevent the growth of bacteria on membrane. The addition of some materials such as natural products was one of those approaches. In this work, myrrh was chosen because it is well known as an antibacterial natural product. Unmodified RO membrane was prepared in the lab using interfacial polymerization between trimesoyl chloride (TMC, 0.1 M) and m-phenylenediamine (MPD, 0.3 M). The characterization was obtained by using infrared (IR) and scanning electron microscopy (SEM). The properties of RO membrane as water flux and salt rejection were determined using lake water. The obtained results were 25 and 65% for water flux and salt rejection, respectively. In respect of modified RO membrane, myrrh solution with different concentrations was prepared and mixed with membrane materials. The modified membrane was characterized with IR and SEM. Water flux and salt rejection were determined obtaining results of 42 and 41% for water flux and salt rejection, respectively. The resistance of bacterial growth was tested for both modified and unmodified membranes, showing that the modified membrane presented high resistance of bacterial growth in contrast to the unmodified one.

Total synthesis of the antibacterial polyketide natural product thailandamide lactone.

Stereoselective total synthesis of the structurally intriguing polyketide natural product thailandamide lactone was accomplished, and done so using a convergent approach for the first time to the best of our knowledge. The key features of this synthesis included use of a Crimmins acetate aldol reaction, Evans methylation, Urpi acetal aldol reaction, Sharpless asymmetric epoxidation and subsequent γ-lactonization for the installation of six asymmetric centers and the use of the Negishi reaction, Julia-Kocienski olefination, cross metathesis, HWE olefination and intermolecular Heck coupling for construction of a variety of unsaturated linkages. Pd(i)-based Heck coupling was introduced, for the first time to the best of our knowledge, quite efficiently to couple the major eastern and sensitive western segments of the molecule. The antibacterial activity of thailandamide lactone was also evaluated.