Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome.

Sarecycline is a new narrow-spectrum tetracycline-class antibiotic approved for the treatment of acne vulgaris. Tetracyclines share a common four-ring naphthacene core and inhibit protein synthesis by interacting with the 70S bacterial ribosome. Sarecycline is distinguished chemically from other tetracyclines because it has a 7-[[methoxy(methyl)amino]methyl] group attached at the C7 position of ring D. To investigate the functional role of this C7 moiety, we determined the X-ray crystal structure of sarecycline bound to the Thermus thermophilus 70S ribosome. Our 2.8-Å resolution structure revealed that sarecycline binds at the canonical tetracycline binding site located in the decoding center of the small ribosomal subunit. Importantly, unlike other tetracyclines, the unique C7 extension of sarecycline extends into the messenger RNA (mRNA) channel to form a direct interaction with the A-site codon to possibly interfere with mRNA movement through the channel and/or disrupt A-site codon-anticodon interaction. Based on our biochemical studies, sarecycline appears to be a more potent initiation inhibitor compared to other tetracyclines, possibly due to drug interactions with the mRNA, thereby blocking accommodation of the first aminoacyl transfer RNA (tRNA) into the A site. Overall, our structural and biochemical findings rationalize the role of the unique C7 moiety of sarecycline in antibiotic action.

Diastereomer recognition of three pairs of tetracyclines by electrospray ionization mass spectrometry.

RATIONALE: Stereoisomer profiling is always a difficult issue. Based on the difference between diastereomers, usually because of steric hindrance, isomers can be differentiated by mass spectrometry (MS), although it is often not an easy task. In the current study, tetracycline, chlortetracycline and doxycycline could be distinguished from their respective 4-epimers by MS. METHODS: The electrospray ionization tandem mass spectrometry (ESI-MSn ) analyses were carried out on a Bruker 3000plus ion trap mass spectrometer. For MS/MS experiments, the collision energy was set between 0.18 and 0.45 V to perform energy-resolved mass spectrometry (ERMS). Test solutions were prepared in methanol/water (90:10, v/v) at a concentration of 10 µg/mL. RESULTS: Compared with the collision-induced dissociation (CID) spectrum of protonated tetracycline, the most abundant peak changed from m/z 427 to m/z 410 for 4-epitetracycline. For chlortetracycline and its 4-epimer, differences in relative abundance were observed too. In the CID spectrum of a fragment ion of doxycycline, the abundance of m/z 154 was relatively higher than for the 4-epimer, showing the same trend as in the CID spectra of the other two pairs of tetracyclines. CONCLUSIONS: The CID spectra of tetracycline and chlortetracycline were different from those of their 4-epimers. The CID spectra of protonated doxycycline and its 4-epimer showed only a subtle difference, but the m/z 154 fragment ion in the CID spectra of the fragment ion at m/z 428 offers the possibility to differentiate both epimers.

Functionalized Zirconium Organic Frameworks as Fluorescent Probes for the Detection of Tetracyclines in Water and Pork.

The overuse of tetracyclines (TCs) in livestock breeding may cause a series of health and environmental problems. It is necessary to develop more accurate, convenient, and rapid sensing methods toward TCs, but it is still very challenging. In this work, three isostructural zirconium organic frameworks (Zr-MOFs) have been investigated as probes for the fluorescent sensing of TCs in water. By varying the functional group at the central benzene core, their sensing performances toward TCs can be modified. Under optimized conditions, the limit of detection can be as low as 0.08 nM in a wide detection range of 0-147 µM with high sensitivity and selectivity. These Zr-MOFs can also be applied in the detection of TCs in real pork samples with satisfying reliabilities and correctness. This work provides a new method for the design and optimization of fluorescent sensors toward TCs.

Natural thymol-based ternary deep eutectic solvents: Application in air-bubble assisted-dispersive liquid-liquid microextraction for the analysis of tetracyclines in water.

Four new thymol-based ternary deep eutectic solvents were prepared and evaluated as the extractive phase in air-bubbles assisted dispersive liquid-liquid microextraction for extraction of tetracycline, doxycycline, and oxytetracycline from the water before high-performance liquid chromatography. The maximum extraction efficiencies were obtained using 400 µL of [choline chloride]:[thymol]:[nonanoic acid] in the molar ratio of 1:2:2 at pH = 5. The solvent was characterized by FTIR and NMR spectroscopy. The hydrophobicity of the deep eutectic solvent and its effect on the pH of water samples after mixing was also studied. Besides, the extraction efficiency of the ternary deep eutectic solvent was compared with that of two binary thymol-based deep eutectic solvents, including [choline chloride]:[thymol] and [thymol]:[nonanoic acid] at the same conditions. Under optimal conditions, limits of detection and quantification were 1.2-8.0 and 3.8-26.6 µg/L, respectively. The linear ranges were 18.2-500 µg/L for oxytetracycline, 26.6-500 µg/L for tetracycline, and 3.8-500 µg/L for doxycycline with the determination coefficients > 0.9912. Intra- and inter-day relative standard deviations were 1.2-3.8 and 7.7-11.2%, respectively. The developed method was applied to the analysis of tetracyclines in unspiked and spiked environmental water samples, and the obtained recoveries were 74.5-95.4% with relative standard deviations of 1.2-4.0%.

Development of a surfactant-assisted dispersive solid phase extraction using deep eutectic solvent to extract four tetracycline antibiotics residues in milk samples.

In this study, a new floating dispersive solid phase extraction method based on deep eutectic solvents has been developed in a home-made extraction device for the extraction of four tetracycline antibiotics from milk samples. In this approach, the sorbent (activated carbon) was dispersed in whole parts of solution with the aid of air stream and floated on top of the solution with the aid of the surfactant (lauryl betaine) and air bubbles. After collection of the sorbent, the adsorbed analytes were eluted with tetrabutyl ammonium chloride-propionic acid deep eutectic solvent under sonication. In this method, there was no need of organic dispersive and extraction solvents and the used sorbent was collected on top of the solution and collected without centrifugation. The validation parameters showed that low limits of detection (0.1-0.3 µg/kg) and quantification (0.6-1.0 µg/kg), acceptable enrichment factors (52-60), efficient extraction recoveries (80-91%), and satisfactory relative standard deviations (≤9.8%) were obtained. Eventually, the method was successfully applied on different milk samples and tetracycline was determined in them.

Carboxylation modified meso-porous carbon aerogel templated by ionic liquid for solid-phase microextraction of trace tetracyclines residues using HPLC with UV detection.

A carbon aerogel composite templated and catalyzed by ionic liquid was fabricated to obtain a meso-porous and cross-linked structure while avoiding the freeze and supercritical drying. It was then carboxylated to obtain favorable surface groups. The easily prepared material displayed excellent extraction effect of six tetracyclines (TCs) compared to the non-carboxylated carbon aerogel. A direct immersion solid-phase microextraction method to determine six TCs in aqueous samples was developed coupling with high-performance liquid chromatography (HPLC) with UV-Vis detector set at 355 nm. The experimental parameters affecting the analytical performance of this method, including sample pH, ionic strength, extraction and desorption time, extraction volume, and temperature, were optimized. Adsorption kinetics and thermodynamics models were used to clarify the extraction mechanism. Under the optimized conditions, this method has a wide linear range of 2-1000 µg L-1, low limits of detection of 0.36-0.71 µg L-1, repeatability of 1.85-10.96%, and reproducibility of 4.92-13.47% for six TCs. The method was successfully applied to detect TC residues in egg and poultry farm wastewater samples.

Bacterial natural products in the fight against mosquito-transmitted tropical diseases.

Covering: up to 2019 Secondary metabolites of microbial origin have long been acknowledged as medically relevant, but their full potential remains largely unexploited. Of the countless natural compounds discovered thus far, only 5-10% have been isolated from microorganisms. At the same time, while whole-genome sequencing has demonstrated that bacteria and fungi often encode natural products, only a few genera have yet been mined for new compounds. This review explores the contributions of bacterial natural products to combatting infection by malaria parasites, filarial worms, and arboviruses such as dengue, Zika, Chikungunya, and West Nile. It highlights how molecules isolated from microorganisms ranging from marine cyanobacteria to mosquito endosymbionts can be exploited as antimicrobials and antivirals. Pursuit of this mostly untapped source of chemical entities will potentially result in new interventions against these tropical diseases, which are urgently needed to combat the increase in the incidence of resistance.

Microbial degradation of tetracycline in the aquatic environment: a review.

Tetracycline residues have frequently been detected in multi-environmental media, and it could induce antibiotic resistance genes (ARGs) in microorganisms, which has attracted great attention. Where biodegradation processes may be a promising strategy to remove tetracycline. Thus, this study mainly considers: (i) the degradation of tetracycline by microorganisms including single microorganisms and microbial flora; (ii) the elimination of tetracycline during biochemical treatment processes and advanced treatment systems in wastewater treatment plants (WWTPs) and constructed wetlands (CWs); (iii) the degradation of tetracycline by biological coupling processes; (iv) the confusion and problem of tetracycline biodegradation. Furthermore, the characteristics and comparison of tetracycline biodegradation have been discussed in detail. Additionally, future research directions are suggested to reduce tetracycline in the aquatic environment, especially tetracycline biodegradation and the nitrogen conversion process. Highlights Degradation of tetracycline by pure culture strains and microflora was significant. Degradation of tetracycline by biochemical treatment process was summarized. Advanced treatment process in CWs could eliminate tetracycline. Future research directions on biodegradation of tetracycline are proposed.

Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study.

The recent outbreak of novel coronavirus disease-19 (COVID-19) calls for and welcomes possible treatment strategies using drugs on the market. It is very efficient to apply computer-aided drug design techniques to quickly identify promising drug repurposing candidates, especially after the detailed 3D structures of key viral proteins are resolved. The virus causing COVID-19 is SARS-CoV-2. Taking advantage of a recently released crystal structure of SARS-CoV-2 main protease in complex with a covalently bonded inhibitor, N3 (Liu et al., 10.2210/pdb6LU7/pdb), I conducted virtual docking screening of approved drugs and drug candidates in clinical trials. For the top docking hits, I then performed molecular dynamics simulations followed by binding free energy calculations using an end point method called MM-PBSA-WSAS (molecular mechanics/Poisson-Boltzmann surface area/weighted solvent-accessible surface area; Wang, Chem. Rev. 2019, 119, 9478; Wang, Curr. Comput.-Aided Drug Des. 2006, 2, 287; Wang; ; Hou J. Chem. Inf. Model., 2012, 52, 1199). Several promising known drugs stand out as potential inhibitors of SARS-CoV-2 main protease, including carfilzomib, eravacycline, valrubicin, lopinavir, and elbasvir. Carfilzomib, an approved anticancer drug acting as a proteasome inhibitor, has the best MM-PBSA-WSAS binding free energy, -13.8 kcal/mol. The second-best repurposing drug candidate, eravacycline, is synthetic halogenated tetracycline class antibiotic. Streptomycin, another antibiotic and a charged molecule, also demonstrates some inhibitory effect, even though the predicted binding free energy of the charged form (-3.8 kcal/mol) is not nearly as low as that of the neutral form (-7.9 kcal/mol). One bioactive, PubChem 23727975, has a binding free energy of -12.9 kcal/mol. Detailed receptor-ligand interactions were analyzed and hot spots for the receptor-ligand binding were identified. I found that one hot spot residue, His41, is a conserved residue across many viruses including SARS-CoV, SARS-CoV-2, MERS-CoV, and hepatitis C virus (HCV). The findings of this study can facilitate rational drug design targeting the SARS-CoV-2 main protease.

Discovery of a novel analogue of FR901533 and the corresponding biosynthetic gene cluster from Streptosporangium roseum No. 79089.

FR901533 (1, also known as WS79089B), WS79089A (2), and WS79089C (3) are polycyclic aromatic natural products with promising inhibitory activity to endothelin-converting enzymes. In this work, we isolated five tridecaketide products from Streptosporangium roseum No. 79089, including 1-3, benaphthamycin (4) and a novel FR901533 analogue (5). The structure of 5 was characterized based on spectroscopic data. Compared with the major product 2, the new compound 5 has an additional hydroxyl group at C-12 and an extra methyl group at the 13-OH. The configuration of C-19 of these compounds was determined to be R using Mosher's method. A putative biosynthetic gene cluster for compounds 1-5 was discovered by analyzing the genome of S. roseum No. 79089. This 38.6-kb gene cluster contains 38 open reading frames, including a minimal polyketide synthase (wsaA-C), an aromatase (wsaD), three cyclases (wsaE, F, and W), and a series of tailoring enzymes such as monooxygenases (wsaO1-O7) and methyltransferases (wsaM1 and M2). Disruption of the ketosynthase gene (wsaA) in this gene cluster abolished the production of 1-5, confirming that this gene cluster is indeed responsible for the biosynthesis of 1-5. A type II polyketide biosynthetic pathway was proposed for this group of natural endothelin-converting enzyme inhibitors. KEY POINTS: • Five aromatic tridecaketides were isolated from Streptosporangium roseum No. 79089. • A novel FR901533 analogue, 12-hydroxy-13-O-methyl-WS79089A, was characterized. • The absolute configuration of C-19 of FR901533 and analogues was determined. • The biosynthetic gene cluster of FR901533 and analogues was discovered.

Preparation of hydrophilic molecularly imprinted solid-phase microextraction fiber for the selective removal and extraction of trace tetracyclines residues in animal derived foods.

The present work reported a novel hydrophilic and selective solid-phase microextraction fiber by improved multiple co-polymerization method immobilization of tetracycline molecularly imprinted polymer on a stainless steel wire and directly coupled with high-performance liquid chromatography for sensitive determination of trace tetracyclines residues in animal derived foods. The developed molecularly imprinted polymer coated solid-phase microextraction fibers were characterized through scanning electron microscopy, Fourier transfer infrared spectroscopy, thermogravimetric analysis, and adsorption experiments, the fiber with cross-linked and porous structure was observed and high thermal and chemical stability. The maximum adsorption capacity of this fiber with good selectivity reached 2.35 µg/mg in aqueous matrices, and showed good repeatability (relative standard deviation ≤ 6.6%, n = 5) and satisfying reproducibility between fiber to fiber (relative standard deviation ≤ 7.8%, n = 5). Under the optimized solid-phase microextraction conditions, satisfactory linearity (5-1000 µg/L) and detection limits (0.38-0.72 µg/kg, S/N = 3) for all the tetracyclines were obtained. The practicality of this method was proved by adding tetracycline, oxytetracycline at three levels to milk, chicken, and fish samples with good recoveries of 77.3-104.4%.

Omadacycline: A Modernized Tetracycline.

When tetracyclines were introduced in the 1940s, these antibiotics offered a broad spectrum of activity against multiple types of pathogens. However, their utility waned after the selection of tetracycline resistance in the pathogens against which they were effective. Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class of antibiotics that is unaffected by these resistance mechanisms. It has an appropriate spectrum of activity for community-acquired infections, including those caused by many resistant organisms. Omadacycline offers a well-tolerated treatment for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Omadacycline has minimal known drug-drug interactions, and should be administered in a fasting state, avoiding dairy and cation-containing products for at least 4 hours after dosing. It does not require dose adjustments for sex, age, or hepatic or renal impairment, and has a safety profile similar to that of other oral tetracyclines. Because omadacycline can be administered effectively orally, it can help reduce hospitalization costs associated with intravenous antibiotic administration. This special supplement to Clinical Infectious Diseases offers an in-depth examination of omadacycline development, including discussions of pharmacokinetic and pharmacodynamic trials, spectrum of activity and preclinical data, early clinical trials, phase III clinical trials, and an integrated safety summary.

Omadacycline: A Novel Tetracycline Derivative With Oral and Intravenous Formulations.

Omadacycline, an aminomethylcycline, is a novel member of the tetracycline class of antibiotics. It has received approval by the US Food and Drug Administration for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, and is available in both oral and intravenous formulations. It is also being evaluated in clinical trials for the treatment of cystitis and pyelonephritis. The omadacycline molecule was designed to overcome tetracycline resistance and has broad-spectrum activity that includes gram-positive bacteria, gram-negative bacteria, anaerobes, atypicals, and other drug-resistant strains, like methicillin-resistant Staphylococcus aureus, as well as Yersinia pestis and Bacillus anthracis, organisms of biodefense interest. Omadacycline has minimal drug-drug pharmacokinetic interactions and a favorable safety profile, with the most common adverse events being gastrointestinal symptoms.

Carboxyl Fe3O4 magnetic nanoparticle-based SPE and HPLC method for the determination of six tetracyclines in water.

A novel carboxyl Fe3O4 magnetic nanoparticle-based solid-phase extraction combined with high-performance liquid chromatography was developed for the analysis of oxytetracycline, tetracycline, demeclocycline, metacycline, chlortetracycline, and doxycycline in water samples. Driven by the electrostatic interaction and the strong chelation between tetracyclines and iron ions, tetracyclines in samples were adsorbed onto the adsorbents. The adsorbed analytes were subsequently eluted with oxalic acid and separated with a C18 column under gradient condition with a mobile phase consisting of methanol, acetonitrile, and oxalic acid at a flow rate of 0.5 mL/min. The detection was performed at variable ultraviolet wavelengths. Under optimized conditions, the developed method gave an enrichment factor of 33.3, linearity ranges of 5.00-1000 µg/L, detection limits of (2.86-5.19) × 10-2 µg/L, quantification limits of (9.54-17.3) × 10-2 µg/L, recoveries of 76.2-98.0%, and intra- and inter-day RSDs of 0.132-15.5% and 2.28-14.5% for these tetracyclines. The established method was successfully applied for the determination of these six tetracyclines in tap water, river water, pond water, and lake water samples. Graphical abstract ᅟ.

Effect of thermal treatment of whey contaminated with antibiotics on the growth of Kluyveromyces marxianus.

The objective of the studies reported in this research communication was to investigate the use of whey contaminated with antibiotics such as cephalosporins, quinolones and tetracyclines as a nutrient medium for the growth of Kluyveromyces marxianus with particular attention to the effect of thermal treatment used to overcome the inhibitory effects of antibiotic concentrations close to the Maximum Residue Limits. The heat treatments at 120 °C for 40 min, 120 °C for 83 min, and 120 °C for 91 min caused total inactivation of cephalosporins, tetracyclines and quinolone residues in whey respectively.

Preparation of low-cost sludge-based mesoporous carbon and its adsorption of tetracycline antibiotics.

Preparation of sludge-derived mesoporous carbon materials (SMCs) through pyrolysis of excess activated sludge from urban municipal sewage plants is an effective means of reducing pollution and utilizing a waste resource. This paper presented a method of SMC preparation in which calcium oxide (CaO), polyacrylamide (PAM), and chitosan (CAS) flocculating agents were used as pore-forming additives. Physical and chemical characterizations of the prepared SMCs were conducted by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS). The prepared SMCs were used to adsorb a tetracycline (TC) antibiotic pollutant. The influences of pH, adsorption time, temperature, and pollutant concentration on TC adsorption capacity were determined. The experiments demonstrated that weakly acidic conditions were conducive to TC adsorption, which mainly occurs via electrostatic and π-π interactions. The TC adsorption process by SMCs conformed better to the pseudo-second-order models, indicating that chemical adsorption was the dominant adsorption process. The isothermal adsorption of TC by the SMCs conformed to the Freundlich model. This implied that TC easily adhered onto the SMC surfaces via multilayer homogeneous adsorption. Thermodynamic studies revealed that the adsorption of TC onto SMCs was spontaneous and endothermic.

A Yeast Three Hybrid Assay for Metabolic Engineering of Tetracycline Derivatives.

Metabolic engineering stands to transform the discovery and production of a wide range of chemicals, but metabolic engineering currently demands considerable resource investments that restrict commercial application. To facilitate the applicability of metabolic engineering, general high-throughput and readily implemented technologies are needed to assay vast libraries of strains producing desirable chemicals. Toward this end, we describe here the development of a yeast three hybrid (Y3H) assay as a general, high-throughput, versatile and readily implemented approach for the detection of target molecule biosynthesis. Our system detects target molecule biosynthesis through a change in reporter gene transcription that results from the binding of the target molecule to a modular protein receptor. We demonstrate the use of the Y3H assay for detecting the biosynthesis of tetracyclines, a major class of antibiotics, based on the interaction between tetracyclines and the tetracycline repressor protein (TetR). Various tetracycline derivatives can be detected using our assay, whose versatility enables its use both as a screen and a selection to match the needs and instrumentation of a wide range of end users. We demonstrate the applicability of the Y3H assay to metabolic engineering by differentiating between producer and nonproducer strains of the natural product tetracycline TAN-1612. The Y3H assay is superior to state-of-the-art HPLC-MS methods in throughput and limit of detection of tetracycline derivatives. Finally, our establishment of the Y3H assay for detecting the biosynthesis of a tetracycline supports the generality of the Y3H assay for detecting the biosynthesis of many other target molecules.

Tetracycline repurposing in neurodegeneration: focus on Parkinson's disease.

The prevalence of Parkinson's disease, which affects millions of people worldwide, is increasing due to the aging population. In addition to the classic motor symptoms caused by the death of dopaminergic neurons, Parkinson's disease encompasses a wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkinson's disease progression are being developed, drug repurposing, which is the use of existing drugs that have passed numerous toxicity and clinical safety tests for new indications, can be used to identify treatment compounds. This strategy has revealed that tetracyclines are promising candidates for the treatment of Parkinson's disease. Tetracyclines, which are neuroprotective, inhibit proinflammatory molecule production, matrix metalloproteinase activity, mitochondrial dysfunction, protein misfolding/aggregation, and microglial activation. Two commonly used semisynthetic second-generation tetracycline derivatives, minocycline and doxycycline, exhibit effective neuroprotective activity in experimental models of neurodegenerative/ neuropsychiatric diseases and no substantial toxicity. Moreover, novel synthetic tetracyclines with different biological properties due to chemical tuning are now available. In this review, we discuss the multiple effects and clinical properties of tetracyclines and their potential use in Parkinson's disease treatment. In addition, we examine the hypothesis that the anti-inflammatory activities of tetracyclines regulate inflammasome signaling. Based on their excellent safety profiles in humans from their use for over 50 years as antibiotics, we propose the repurposing of tetracyclines, a multitarget antibiotic, to treat Parkinson's disease.

Sorption behavior of tetracyclines on suspended organic matters originating from swine wastewater.

Tetracyclines (TCs) discharged from livestock wastewater have aroused public concerns due to their pharmacological threats to ecosystems and human health. As an important medium in the wastewater, suspended organic matters (SOMs) play vital roles in antibiotics transport and degradation. However, limited information has been reported in the relevant literature. This study investigated TCs sorption behavior on SOM, withdrawn from swine wastewater. High TCs sorption capacities were detected, with the maximum values ranging from 0.337 to 0.679mg/g. Increasing pH and temperature led to the decline of sorption capacity. Results from three-dimensional excitation-emission matrix fluorescence spectroscopy and Fourier transform infrared spectrometry revealed that amide and carboxyl groups were the main functional groups for TCs adsorption. The interactions between SOM and TCs were clarified as predominated by hydrogen-bonding and cation-exchange in acid conditions, and electrostatic repulsion in neutral or alkaline conditions. Adsorption kinetics modeling was conducted, and a satisfactory fitting was achieved with the Freundlich equation. These results indicated that the adsorption process was a rather complex process, involving a combination of cation-exchange and hydrogen-bonding. The results will provide a better understanding of the capability of SOM for TCs transport and abatement in the wastewater treatment process.

Asymmetric Alkylation of Anthrones, Enantioselective Total Synthesis of (-)- and (+)-Viridicatumtoxins B and Analogues Thereof: Absolute Configuration and Potent Antibacterial Agents.

A phase transfer catalyzed asymmetric alkylation of anthrones with cyclic allylic bromides using quinidine- or quinine-derived catalysts is described. Utilizing mild basic conditions and as low as 0.5 mol % catalyst loading, and achieving up to >99:1 dr selectivity, this asymmetric reaction was successfully applied to produce enantioselectively (-)- and (+)-viridicatumtoxins B, and thus allowed assignment of the absolute configuration of this naturally occurring antibiotic. While the developed asymmetric synthesis of C10 substituted anthrones is anticipated to find wider applications in organic synthesis, its immediate application to the construction of a variety of designed enantiopure analogues of viridicatumtoxin B led to the discovery of highly potent, yet simpler analogues of the molecule. These studies are expected to facilitate drug discovery and development efforts toward new antibacterial agents.