Discovery Of New Antibacterial Drugs Research Articles

Enhancing effect of natural adjuvant, panduratin A, on antibacterial activity of colistin against multidrug-resistant Acinetobacter baumannii

Colistin- and carbapenem-resistant Acinetobacter baumannii is a serious multidrug resistant (MDR) bacterium in clinical settings. Discovery of new antibacterial drugs against MDR is facing multiple challenges in drug development. Combination of known antibiotics with a robust adjuvant might be an alternative effective strategy for MDR treatment. In the study herein, we report an antibiotic adjuvant activity of a natural compound panduratin A from fingerroot (Boesenbergia rotunda) as a potent adjuvant to colistin. The present study investigated the antibiotic adjuvant effect of panduratin A against 10 colistin- and carbapenem-resistant A. baumannii. Antibacterial activities were tested by broth microdilution method. Biofilm assay was used to determine the efficacy of panduratin A in biofilm formation inhibition on two representative strains Aci46 and Aci44. Genomic and transcriptomic analyses of colistin- and carbapenem-resistant A. baumannii strains were used to identify potential resistance and tolerance mechanism in the bacteria. Panduratin A-colistin combination showed an increased effect on antibacterial in the A. baumannii. However, panduratin A did not improve the antibacterial activity of imipenem. In addition, panduratin A improves anti-biofilm activity of colistin against Aci44 and Aci46, the colistin- and carbapenem-resistant A. baumannii. Panduratin A markedly enhances bactericidal and anti-biofilm activity of colistin against colistin- resistant A. baumannii. Based on genome comparisons, single nucleotide polymorphism (SNP) patterns in six genes encoding biofilm and lipid A biosynthesis were shared in Aci44 and Aci46. In Aci44, we identified a partial sequence of pmrB encoding a polymyxin resistant component PmrB, whereas a full length of pmrB was observed in Aci46. RNA-seq analyses of Aci44 revealed that panduratin A-colistin combination induced expression of ribosomal proteins and oxidative stress response proteins, whereas iron transporter and MFS-type transporter systems were suppressed. Panduratin A-colistin combination could promote intracellular reactive oxygen species (ROS) accumulation could lead to the cidal effect on colistin-resistant A. baumannii. Combination of panduratin A and colistin showed a significant increase in colistin efficacy against colistin- resistant A. baumannii in comparison of colistin alone. Genomic comparison between Aci44 and Aci46 showed mutations and SNPs that might affect different phenotypes. Additionally, based on RNA-Seq, panduratin A-colistin combination could lead to ROS production and accumulation. These findings confirmed the potency of panduratin as colistin adjuvant against multidrug resistant A. baumannii.

Combinatorial discovery of antibacterials via a feature-fusion based machine learning workflow.

The discovery of new antibacterials within the vast chemical space is crucial in combating drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). However, the traditional approach of screening the entire chemical library in an ergodic manner can be laborious and time-consuming. Machine learning-assisted screening of antibacterials alleviates the exploration effort but suffers from the lack of reliable and related datasets. To address these challenges, we devised a combinatorial library comprising over 110 000 candidates based on the Ugi reaction. A focused library was subsequently generated through uniform sampling of the entire library to narrow down the preliminary screening scale. A novel feature-fusion architecture called the latent space constraint neural network was developed which incorporated both fingerprint and physicochemical molecular descriptors to predict the antibacterial properties. This integration allowed the model to leverage the complementary information provided by these descriptors and improve the accuracy of predictions. Three lead compounds that demonstrated excellent efficacy against MRSA while alleviating drug resistance were identified. This workflow highlights the integration of machine learning with the combinatorial chemical library to expedite high-quality data collection and extensive data mining for antibacterial screening.

Repurposing Selamectin as an Antimicrobial Drug against Hospital-Acquired Staphylococcus aureus Infections.

The emergence of multidrug-resistant strains requires the urgent discovery of new antibacterial drugs. In this context, an antibacterial screening of a subset of anthelmintic avermectins against gram-positive and gram-negative strains was performed. Selamectin completely inhibited bacterial growth at 6.3 μg/mL concentrations against reference gram-positive strains, while no antibacterial activity was found against gram-negative strains up to the highest concentration tested of 50 μg/mL. Given its relevance as a community and hospital pathogen, further studies have been performed on selamectin activity against Staphylococcus aureus (S. aureus), using clinical isolates with different antibiotic resistance profiles and a reference biofilm-producing strain. Antibacterial studies have been extensive on clinical S. aureus isolates with different antibiotic resistance profiles. Mean MIC90 values of 6.2 μg/mL were reported for all tested S. aureus strains, except for the macrolide-resistant isolate with constitutive macrolide-lincosamide-streptogramin B resistance phenotype (MIC90 9.9 μg/mL). Scanning Electron Microscopy (SEM) showed that selamectin exposure caused relevant cell surface alterations. A synergistic effect was observed between ampicillin and selamectin, dictated by an FIC value of 0.5 against methicillin-resistant strain. Drug administration at MIC concentration reduced the intracellular bacterial load by 81.3%. The effect on preformed biofilm was investigated via crystal violet and confocal laser scanning microscopy. Selamectin reduced the biofilm biomass in a dose-dependent manner with minimal biofilm eradication concentrations inducing a 50% eradication (MBEC50) at 5.89 μg/mL. The cytotoxic tests indicated that selamectin exhibited no relevant hemolytic and cytotoxic activity at active concentrations. These data suggest that selamectin may represent a timely and promising macrocyclic lactone for the treatment of S. aureus infections.

Chalcone Derivatives as Antibacterial Agents: An Updated Overview.

The indiscriminate use of antibiotics brings an alarming reality: in 2050, bacterial resistance could be the main cause of death in the world, resulting in the death of 10 million people, according to the World Health Organization (WHO). In this sense, to combat bacterial resistance, several natural substances, including chalcones, have been described in relation to antibacterial, representing a potential tool for the discovery of new antibacterial drugs. The objective of this study is to perform a bibliographic survey and discuss the main contributions in the literature about the antibacterial potential of chalcones in the last 5 years. A search was carried out in the main repositories, for which the publications of the last 5 years were investigated and discussed. Unprecedented in this review, in addition to the bibliographic survey, molecular docking studies were carried out to exemplify the applicability of using one of the molecular targets for the design of new entities with antibacterial activity. In the last 5 years, antibacterial activities were reported for several types of chalcones, for which activities were observed for both gram-positive and gram-negative bacteria with high potency, including MIC values in the nanomolar range. Molecular docking simulations demonstrated important intermolecular interactions between chalcones and residues from the enzymatic cavity of the enzyme DNA gyrase, one of the validated molecular targets in the development of new antibacterial agents. The data presented demonstrate the potential of using chalcones in drug development programs with antibacterial properties, which may be useful to combat resistance, a worldwide public health problem.

Marine Based Natural Products: Exploring the Recent Developments in the Identification of Antimicrobial Agents.

The marine ecosystem is the less explored, biologically diverse, and vastest resource to discover novel antimicrobial agents. In recent decades' antimicrobial drugs are losing their effectiveness due to the growing resistance among pathogens, which causes diseases to have considerable death rates across the globe. Therefore, there is a need for the discovery of new antibacterials that can reach the market. There is a gradual growth of compounds from marine sources which are entering the clinical trials. Thus, the prominence of marine natural products in the field of drug design and discovery across the academia and pharmaceutical industry is gaining attention. Herein, the present review covers nearly 200 marine based antimicrobial agents of 11 structural classes discovered from the year 2010 to 2022. All the discussed compounds have exhibited medium to high antimicrobial activity in inhibiting various microorganisms.

Synthesis and Characterization of Novel 2-Acyl-3-trifluoromethylquinoxaline 1,4-Dioxides as Potential Antimicrobial Agents.

The emergence of drug resistance in pathogens leads to a loss of effectiveness of antimicrobials and complicates the treatment of bacterial infections. Quinoxaline 1,4-dioxides represent a prospective scaffold for search of new compounds with improved chemotherapeutic characteristics. Novel 2-acyl-3-trifluoromethylquinoxaline 1,4-dioxides with alteration of substituents at position 2 and 6 were synthesized via nucleophilic substitution with piperazine moiety and evaluated against a broad panel of bacteria and fungi by measuring their minimal inhibitory concentrations. Their mode of action was assessed by whole-genomic sequencing of spontaneous drug-resistant Mycobacterium smegmatis mutants, followed by comparative genomic analysis, and on an original pDualrep2 system. Most of the 2-acyl-3-trifluoromethylquinoxaline 1,4-dioxides showed high antibacterial properties against Gram-positive strains, including mycobacteria, and the introduction of a halogen atom in the position 6 of the quinoxaline ring further increased their activity, with 13c being the most active compound. The mode of action studies confirmed the DNA-damaging nature of the obtained quinoxaline 1,4-dioxides, while drug-resistance may be provided by mutations in redox homeostasis genes, encoding enzymes potentially involved in the activation of the compounds. This study extends views about the antimicrobial and antifungal activities of the quinoxaline 1,4-dioxides and can potentially lead to the discovery of new antibacterial drugs.

Potential therapeutic targets from Mycobacterium abscessus (Mab): recently reported efforts towards the discovery of novel antibacterial agents to treat Mab infections.

Mycobacterium abscessus (Mab) are rapidly growing mycobacteria that cause severe and persistent infections in both skin and lung tissues. Treatment regimens involve the extended usage of complex combinations of drugs, often leading to severe adverse side effects, particularly in immunocompromised patients. Current macrolide therapies are gradually proving to be less effective, largely due to emergence of antibiotic resistance; there is therefore an increasing need for the discovery of new antibacterials that are active against Mab. This review highlights recent research centred upon a number of potential therapeutic targets from Mab (Ag85C, ClpC1, GyrB, MmpL3 and TrmD), and discusses the various approaches used to discover small molecule inhibitors, in the search for future antibiotics for the treatment of Mab infections.

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs.

Bacterial resistance has become increasingly serious because of the widespread use and abuse of antibiotics. In particular, the emergence of multidrug-resistant bacteria has posed a serious threat to human public health and attracted the attention of the World Health Organization (WHO) and the governments of various countries. Therefore, the establishment of measures against bacterial resistance and the discovery of new antibacterial drugs are increasingly urgent to better contain the emergence of bacterial resistance and provide a reference for the development of new antibacterial drugs. In this review, we discuss some antibiotic drugs that have been approved for clinical use and a partial summary of the meaningful research results of anti-drug resistant bacterial drugs in different fields, including the antibiotic drugs approved by the FDA from 2015 to 2020, the potential drugs against drug-resistant bacteria, the new molecules synthesized by chemical modification, combination therapy, drug repurposing, immunotherapy and other therapies.

The Biology of Colicin M and Its Orthologs.

The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial. Colicins, due to their antibacterial properties, thus constitute good candidates. These toxin proteins, produced by E. coli to kill enteric relative competitors, exhibit cytotoxicity through ionophoric activity or essential macromolecule degradation. Among the 25 colicin types known to date, colicin M (ColM) is the only one colicin interfering with peptidoglycan biosynthesis. Accordingly, ColM develops its lethal activity in E. coli periplasm by hydrolyzing the last peptidoglycan precursor, lipid II, into two dead-end products, thereby leading to cell lysis. Since the discovery of its unusual mode of action, several ColM orthologs have also been identified based on sequence alignments; all of the characterized ColM-like proteins display the same enzymatic activity of lipid II degradation and narrow antibacterial spectra. This publication aims at being an exhaustive review of the current knowledge on this new family of antibacterial enzymes as well as on their potential use as food preservatives or therapeutic agents.

Chemical Composition and Antimicrobial Activity of Two Sri Lankan Lichens, Parmotrema rampoddense, and Parmotrema tinctorum against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus.

Introduction Medicinal utility of lichens is ascribed to the presence of various secondary metabolites of low molecular weight and they have been used in traditional medicine including Ayurveda in the treatment of wounds and skin disorders. Despite the urgent need to effectively address the antibiotic resistance worldwide, the discovery of new antibacterial drugs has declined in the recent past. This emphasizes the increasing importance of investigating and developing new classes of antibiotics that can withstand antibiotic resistance. Aims of the study. The present study was conducted to investigate the chemical composition and the antibacterial activity of hexane, ethanol, and aqueous extracts of Parmotrema rampoddense and Parmotrema tinctorum, two lichens collected from Belihuloya, Sri Lanka, against Gram-negative and Gram-positive bacteria including twenty clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). Materials and methods. Phytochemical analysis, thin layer chromatography (TLC), and Gas Chromatography Mass Spectrometry (GC-MS) were performed to determine the chemical composition of the two lichens. Hexane, ethanol, and aqueous extracts of both lichens were tested against clinical isolate of Gram-negative and Gram-positive bacteria including twenty clinical isolates of MRSA. Bacterial susceptibility was tested using a disc diffusion assay. Minimum inhibitory concentration (MIC) was determined by a broth microdilution method. Vancomycin was used as the positive control. Results Alectorialic acid, atranorin, atraric acid, orcinol, and O-orsellinaldehyde were among the secondary metabolites identified by the TLC and GC-MS analysis. None of the lichen extracts were active against Gram-negative bacteria but both lichens showed a concentration-dependent activity against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA. Ethanol extract of P. rampoddense showed the highest activity against MSSA with the MIC, 0.0192 mg/ml, but all MRSA isolates investigated showed MIC between 0.096 and 2.4 mg/ml for the same extract. Conclusion Both lichens, P. rampoddense and P. tinctorum, represent potentially important sources of future antimicrobial drugs. Further investigation on the ethanol extract of P. rampoddense will enable us to determine the most active phytoconstituents responsible for the activity, their mechanism of action against bacterial pathogens, and also their cytotoxicity against normal cells.

Cheminformatics Analysis of Fluoroquinolones and their Inhibition Potency Against Four Pathogens.

Drug-resistant bacteria are a worldwide public health concern. As the prevalence of multi-drug resistant pathogens outpaces the discovery of new antibacterials, it is of importance to explore the structure-activity relationships for series of known bactericides with proven scaffolds. Herein, we assembled a set of 507 fluoroquinolone analogues all experimentally tested for their inhibition potency against four pathogens: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. We relied on cheminformatics techniques to characterize and cluster them based on their structural similarity and analyzed the structure-activity relationships identified for each cluster of fluoroquinolones. Then, we utilized machine learning techniques to develop and validate predictive QSAR models for computing the inhibition potencies (pMIC) of analogues for each pathogen. These QSAR models afforded reasonable external prediction performances (R2≥0.6, MAE∼0.4). This study confirmed that (i) there are both global and local inter-pathogen concordance regarding the antibacterial potency of fluoroquinolones, (ii) small clusters of fluoroquinolone analogues are characterized by unique patterns of strain selectivity and potency, the latter being potentially useful to design new analogues with enhanced potency and/or selectivity towards a given pathogen, and (iii) robust QSAR models were obtained allowing for future design of new bioactive fluoroquinolones.

Defining new chemical space for drug penetration into Gram-negative bacteria.

We live in the era of antibiotic resistance, and this problem will progressively worsen if no new solutions emerge. In particular, Gram-negative pathogens present both biological and chemical challenges that hinder the discovery of new antibacterial drugs. First, these bacteria are protected from a variety of structurally diverse drugs by a low-permeability barrier composed of two membranes with distinct permeability properties, in addition to active drug efflux, making this cell envelope impermeable to most compounds. Second, chemical libraries currently used in drug discovery contain few compounds that can penetrate Gram-negative bacteria. As a result of these challenges, intensive screening campaigns have led to few successes, highlighting the need for new approaches to identify regions of chemical space that are specifically relevant to antibacterial drug discovery. Herein we provide an overview of emerging insights into this problem and outline a general approach to addressing it using prospective analysis of chemical libraries for the ability of compounds to accumulate in Gram-negative bacteria. The overall goal is to develop robust cheminformatic tools to predict Gram-negative permeation and efflux, which can then be used to guide medicinal chemistry campaigns and the design of antibacterial discovery libraries.

Antibacterial Activity of the Iranian Scorpion’s Crude Venom (Odontobuthus bidentatus) on Gram-positive and Gram-negative Bacteria

Background: The venoms of some scorpions are rich in bioactive components that may be used in the development and discovery of new antibacterial drugs. The venoms have many components, such as neurotoxins, salts, proteins and peptides with therapeutic properties, and can rapidly eliminate a broad range of bacteria. This study evaluated the anti-bacterial activity of Odontobuthus bidentatus’ crude venom against typical Gram-positive and negative bacteria, such as Staphylococcus aureus, Bacillus subtilis, and Escherichia coli. Methods: The antibacterial effects of the crude venom were evaluated using Minimal Inhibitory Concentration (MIC) and MTT assays and its IC50 value was determined, using GraphPad software. Results: The crude venom significantly inhibited the growth of both Gram-positive and negative bacteria. Also the MTT results showed that the crude venom significantly reduced the viability of E. Coli, S. Aureus, and B. Subtilis bacteria compared with that for the controls. The IC50 values of the venom for E.coli, S.aureus, and B.subtilis were 30.19, 17.64, and 24.13 µM, respectively. Conclusion: The findings suggest that the venom of O. bidentatus scorpion has antibacterial properties. Also, our results offer preliminary clues toward the development of new antibacterial agents and new drugs with high therapeutic potentials for use in animals and humans.

Bacterial Lipoprotein Biosynthetic Pathway as a Potential Target for Structure-based Design of Antibacterial Agents.

Antibiotic resistance is currently a serious problem for global public health. To this end, discovery of new antibacterial drugs that interact with novel targets is important. The biosynthesis of lipoproteins is vital to bacterial survival and its inhibitors have shown efficacy against a range of bacteria, thus bacterial lipoprotein biosynthetic pathway is a potential target. At first, the literature that covered the basic concept of bacterial lipoprotein biosynthetic pathway as well as biochemical characterization of three key enzymes was reviewed. Then, the recently resolved crystal structures of the three enzymes were retrieved from Protein Data Bank (PDB) and the essential residues in the active sites were analyzed. Lastly, all the available specific inhibitors targeting this pathway and their Structure-activity Relationship (SAR) were discussed. We briefly introduce the bacterial lipoprotein biosynthetic pathway and describe the structures and functions of three key enzymes in detail. In addition, we present much knowledge on ligand recognition that may facilitate structure-based drug design. Moreover, we focus on the SAR of LspA inhibitors and discuss their potency and drug-likeness. This review presents a clear background of lipoprotein biosynthetic pathway and provides practical clues for structure-based drug design. In particular, the most up-to-date knowledge on the SAR of lead compounds targeting this pathway would be a good reference for discovery of a novel class of antibacterial agents.

Dual Escherichia coli DNA Gyrase A and B Inhibitors with Antibacterial Activity.

The emergence of multidrug-resistant bacteria is a global health threat necessitating the discovery of new antibacterials and novel strategies for fighting bacterial infections. We report first-in-class DNA gyrase B (GyrB) inhibitor/ciprofloxacin hybrids that display antibacterial activity against Escherichia coli. Whereas DNA gyrase ATPase inhibition experiments, DNA gyrase supercoiling assays, and in vitro antibacterial assays suggest binding of the hybrids to the E. coli GyrA and GyrB subunits, an interaction with the GyrA fluoroquinolone-binding site seems to be solely responsible for their antibacterial activity. Our results provide a foundation for a new concept of facilitating entry of nonpermeating GyrB inhibitors into bacteria by conjugation with ciprofloxacin, a highly permeable GyrA inhibitor. A hybrid molecule containing GyrA and GyrB inhibitor parts entering the bacterial cell would then elicit a strong antibacterial effect by inhibition of both the GyrA and GyrB subunits of DNA gyrase and potentially slow bacterial resistance development.

Balancing Physicochemical Properties of Phenylthiazole Compounds with Antibacterial Potency by Modifying the Lipophilic Side Chain.

Bacterial resistance to antibiotics is presently one of the most pressing healthcare challenges and necessitates the discovery of new antibacterials with unique chemical scaffolds. However, the determination of the optimal balance between structural requirements for pharmacological action and pharmacokinetic properties of novel antibacterial compounds is a significant challenge in drug development. The incorporation of lipophilic moieties within a compound's core structure can enhance biological activity but have a deleterious effect on drug-like properties. In this Article, the lipophilicity of alkynylphenylthiazoles, previously identified as novel antibacterial agents, was reduced by introducing cyclic amines to the lipophilic side chain. In this regard, substitution with methylpiperidine (compounds 14-16) and thiomorpholine (compound 19) substituents significantly enhanced the aqueous solubility profile of the new compounds more than 150-fold compared to the first-generation lead compound 1b. Consequently, the pharmacokinetic profile of compound 15 was significantly enhanced with a notable improvement in both half-life and the time the compound's plasma concentration remained above its minimum inhibitory concentration (MIC) against methicillin-resistant Staphylococcus aureus (MRSA). In addition, compounds 14-16 and 19 were found to exert a bactericidal mode of action against MRSA and were not susceptible to resistance formation after 14 serial passages. Moreover, these compounds (at 2× MIC) were superior to the antibiotic vancomycin in the disruption of the mature MRSA biofilm. The modifications to the alkynylphenylthiazoles reported herein successfully improved the pharmacokinetic profile of this new series while maintaining the compounds' biological activity against MRSA.

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria.

The increasing emergence of multidrug-resistant pathogens is one of the biggest threats to human health and food security. The discovery of new antibacterials, and in particular the finding of new scaffolds, is an imperative goal to stay ahead of the evolution of antibiotic resistance. Herein we report the synthesis of a 3-decyltetramic acid analogue of the ureido dipeptide natural antibiotic leopolic acid A. The key step in the synthetic strategy is an intramolecular Lacey–Dieckmann cyclization reaction of a linear precursor to obtain the desired 3-alkyl-substituted tetramic acid core. The synthesized analogue is more effective than the parent leopolic acid A against Gram-positive (Staphylococcus pseudintermedius) and Gram-negative (E. coli) bacteria (MIC 8 µg/mL and 64 µg/mL, respectively). Interestingly, the compound shows a significant activity against Staphylococcus pseudintermedius strains expressing a multidrug-resistant phenotype (average MIC 32 µg/mL on 30 strains tested). These results suggest that this molecule can be considered a promising starting point for the development of a novel class of antibacterial agents active also against resistant strains.

Subcellular Chemical Imaging of Antibiotics in Single Bacteria Using C60-Secondary Ion Mass Spectrometry.

The inherent difficulty of discovering new and effective antibacterials and the rapid development of resistance particularly in Gram-negative bacteria, illustrates the urgent need for new methods that enable rational drug design. Here we report the development of 3D imaging cluster Time-of-Flight secondary ion mass spectrometry (ToF-SIMS) as a label-free approach to chemically map small molecules in aggregated and single Escherichia coli cells, with ∼300 nm spatial resolution and high chemical sensitivity. The feasibility of quantitative analysis was explored, and a nonlinear relationship between treatment dose and signal for tetracycline and ampicillin, two clinically used antibacterials, was observed. The methodology was further validated by the observation of reduction in tetracycline accumulation in an E. coli strain expressing the tetracycline-specific efflux pump (TetA) compared to the isogenic control. This study serves as a proof-of-concept for a new strategy for chemical imaging at the nanoscale and has the potential to aid discovery of new antibacterials.

One-Pot Phosphate-Mediated Synthesis of Novel 1,3,5-Trisubstituted Pyridinium Salts: A New Family of S. aureus Inhibitors.

Polysubstituted pyridinium salts are valuable pharmacophores found in many biologically active molecules. Their synthesis typically involves the use of multistep procedures or harsh reaction conditions. Here, we report water-based phosphate mediated reaction conditions that promote the condensation of arylacetaldehydes with amines to give 1,3,5-pyridinium salts. The reaction, carried out at pH 6, provides conditions suitable for the use of less stable aldehydes and amines in this Chichibabin pyridine condensation. The evaluation of selected 1,3,5-trisubstituted pyridinium salts highlighted that they can inhibit the growth of S. aureus in the low μg/mL range. The synthetic accessibility of these compounds and preliminary growth inhibition data may pave the way towards the discovery of new anti-bacterials based on the 1,3,5-trisubstituted pyridinium scaffold.

Iridoids from Canthium subcordatum iso-butanol fraction with potent biological activities

BackgroundThe continuous emergence of multi-drug-resistant bacteria drastically reduces the efficacy of antibiotic armory and, consequently, increases the frequency of therapeutic failure. The discovery of new antibacterial drugs is an urgent need. The present study reports the antibacterial and antioxidant activities of the methanol extract, fractions and iridoids from Canthium subcordatum, a plant traditionally used as antidiabetic, anti-inflammatory, and antimicrobial.MethodsBroth microdilution assay was used to determine minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of extracts and iridoids against Staphylococcus aureus, Vibrio cholerae and Shigella flexneri. Antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and gallic acid equivalent antioxidant capacity (GAEAC) assays. The samples were also tested for their cytotoxicity against human red blood cells (RBC).ResultsThe methanol extract, hexane, ethyl acetate and iso-butanol fractions from C. subcordatum fruits displayed different degrees of antioxidant (EC50 = 62.83–70.17 μg/ml; GAEAC = 45.63–58.23 μg/ml) and antibacterial (MIC = 128–512 μg/ml) activities. Canthiumoside 1(1) and linearin (7) were the most active antioxidant (EC50 = 1.12–2.03 μg/ml; GAEAC = 79.82–92.35 μg/ml) and antibacterial (MIC = 8–64 μg/ml) compounds while the most sensitive bacterium was Staphylococcus aureus. The tested samples were non-toxic to normal cells.ConclusionOur results demonstrated that compounds 1 and 7 were potent antibacterial agents and DPPH/ABTS·+ radical scavengers, so they warrant further investigation.