Antimicrobial Drug Candidates Research Articles

Synthesis, spectroscopic characterization, antimicrobial activity, and computational studies of five and/or six heterocyclic nitrogen rings linked to thienopyrazole moiety

A new series of thienopyrazoles linked to five and/or six heterocyclic nitrogen rings such as pyrazole, triazole-3-thione, oxadiazole, thiazole-2-thione and/or pyrimidone moieties was synthesized starting from 5-amino-1,3-diphenyl-1H-thieno[3,2-c]pyrazole-6-carboxylic acid hydrazide as a key precursor. For the synthesis of new thienopyrazoles 2–13, the carboxylic acid hydrazide derivative 1 served as a crucial intermediary. These novel heterocyclic structures were confirmed by analytical and spectroscopic methods (m.p., IR, 1H NMR, 13C NMR, and MS). The new compounds 2–13 were evaluated for their antimicrobial activity to identify new drug candidates to combat diseases caused by microbial strains. Against numerous bacterial and fungal strains, certain derivatives of the produced compounds 9 and 11 demonstrated impressive antimicrobial activity. Besides, molecular docking of the newly compounds was conducted against methicillin-resistant Staphylococcus aureus (MRSA) (2 × 3f.pdb). Among the series, compounds 9 and 11 exhibited the best binding affinity towards the target enzyme -10.1 and -10.5 kcal/mol, respectively. The optimized structures and molecular orbitals of the best docked compounds were predicted using DFT (Density Functional Theory) analysis. Our findings represented that both derivatives 9 and 11 could be utilized for development antimicrobial drug candidates.

ProT-Diff: A Modularized and Efficient Strategy for De Novo Generation of Antimicrobial Peptide Sequences by Integrating Protein Language and Diffusion Models.

Antimicrobial peptides (AMPs) are a promising solution for treating antibiotic-resistant pathogens. However, efficient generation of diverse AMPs without prior knowledge of peptide structures or sequence alignments remains a challenge. Here, ProT-Diff is introduced, a modularized deep generative approach that combines a pretrained protein language model with a diffusion model for the de novo generation of AMPs sequences. ProT-Diff generates thousands of AMPs with diverse lengths and structures within a few hours. After silico physicochemical screening, 45 peptides are selected for experimental validation. Forty-four peptides showed antimicrobial activity against both gram-positive or gram-negative bacteria. Among broad-spectrum peptides, AMP_2 exhibited potent antimicrobial activity, low hemolysis, and minimal cytotoxicity. An in vivo assessment demonstrated its effectiveness against a drug-resistant E. coli strain in acute peritonitis. This study not only introduces a viable and user-friendly strategy for de novo generation of antimicrobial peptides, but also provides potential antimicrobial drug candidates with excellent activity. It is believed that this study will facilitate the development of other peptide-based drug candidates in the future, as well as proteins with tailored characteristics.

Synthesis, biological assessment and molecular docking study of new sulfur-linked 1,2,4-triazole and 1,2,3-triazole hybrid derivatives as potential DNA gyrase inhibitors

Abstract A series of new pyridine-1,2,4-triazole-tagged 1,2,3-triazole hybrid molecules were obtained. The new compounds were synthesized via click chemistry of 1,2,4-triazole-3-thiopropargyl compounds and various azides. All compounds were fully characterized through their spectroscopic analyses. Furthermore, cytotoxic activity was assessed by screening against three cancer cell lines including human colon carcinoma (HCT116), human cervix carcinoma (HeLa) and human breast adenocarcinoma (MCF7). In addition, antimicrobial assessment against one gram-positive (Staphylococcus aureus ATCC 29,213), two Gram-negative bacteria (Sarcina lutea and Escherichia coli ATCC 25,922) and one fungal (Candida albicans NRRL Y–477) microorganism‏.‏ Molecular docking studies of the synthesized compounds against DNA gyrase were used to identify their binding ability to the target enzyme. The best docked molecules unveiled binding affinities to the target ranging from −9.5 to −8.8 kcal mol−1. The adsorption, distribution, metabolic, excretion, and toxicity (ADME/Tox) and drug-likeness analyses of the best docked compounds were evaluated using in silico techniques. Based on in vitro and in silico findings, these pyridine-1,2,4-triazole-tagged 1,2,3-triazole hybrid molecules may be helpful in designing potential antimicrobial drug candidates.

Comparative study of volatile oil constituents, anti-microbial properties, and antibiofilm activities in Eucalyptus camaldulensis and Eucalyptus globulus: insights from central Saudi Arabia

Eucalyptus is a fragrant plant with a highly volatile oil content grown worldwide. This study investigated the phytochemical and biological features of two Eucalyptus species, E. camaldulensis and E. globulus, cultivated in Central Saudi Arabia. Phytochemical analysis revealed 17 compounds in E. camaldulensis and 13 in E. globulus, with α-pinene and 1,8-cineole being both plants’ most abundant volatile components. The antimicrobial activity revealed that Salmonella typhimurium ATCC 13311 and Candida albicans ATCC 10231 are the most susceptible to E. camaldulensis, with the zone of inhibition diameters (ZIDs) of 17.0 ± 0.2 mm and 22.0 ± 0.3 mm, respectively. In contrast, for E. globulus, methicillin-resistant Staphylococcus aureus and Candida albicans ATCC 10231 were the most susceptible, with ZIDs of 13.0 ± 0.2 mm and 20.0 ± 0.2 mm, respectively. E. camaldulensis had minimum inhibitory concentration (MIC) range from 1.56 to 12.5 μL/mL, minimum biocidal concentration (MBC) range from 3.125 to 25.0 μL/mL, minimum biofilm inhibitory concentration (MBIC) range from 3.125 to 25.0 μL/mL, and minimum biofilm eradication concentration (MBEC) from 6.25 to 50.0 μL/mL, while E. globulus had MIC range from 3.125 to 12.5 μL/mL, MBC range from 6.25 to 25.0 μL/mL, MBIC range from 6.25 to 25.0 μL/mL, and MBEC range from 12.5 to 50.0 μL/mL, for the tested organisms. E. camaldulensis demonstrated better antimicrobial activity than E. globulus against the tested organisms, making it a promising antimicrobial drug candidate. Further research is required to determine its effectiveness in treating different human infections.

Synthesis, in silico and in vitro antimicrobial efficacy of substituted arylidene-based quinazolin-4(3H)-one motifs.

Introduction: Quinazolin-4(3H)-one derivatives have attracted considerable attention in the pharmacological profiling of therapeutic drug targets. The present article reveals the development of arylidene-based quinazolin-4(3H)-one motifs as potential antimicrobial drug candidates. Methods: The synthetic pathway was initiated through thermal cyclization of acetic anhydride on anthranilic acid to produce 2-methyl-4H-3,1-benzoxazan-4-one 1, which (upon condensation with hydrazine hydrate) gave 3-amino-2-methylquinazolin-4(3H)-one 2. The reaction of intermediate 2 at its amino side arm with various benzaldehyde derivatives furnished the final products, in the form of substituted benzylidene-based quinazolin-4(3H)-one motifs 3a-l, and with thiophene-2-carbaldehyde to afford 3m. The purified targeted products 3a-m were effectively characterized for structural authentication using physicochemical parameters, microanalytical data, and spectroscopic methods, including IR, UV, and 1H- and 13C-NMR, as well as mass spectral data. The substituted arylidene-based quinazolin-4(3H)-one motifs 3a-m were screened for both in silico and in vitro antimicrobial properties against selected bacteria and fungi. The in silico studies carried out consisted of predicted ADMET screening, molecular docking, and molecular dynamics (MD) simulation studies. Furthermore, in vitro experimental validation was performed using the agar diffusion method, and the standard antibacterial and antifungal drugs used were gentamicin and ketoconazole, respectively. Results and discussion: Most of the compounds possessed good binding affinities according to the molecular docking studies, while MD simulation revealed their levels of structural stability in the protein-ligand complexes. 2-methyl-3-((thiophen-2-ylmethylene)amino) quinazolin-4(3H)-one 3m emerged as both the most active antibacterial agent (with an minimum inhibitory concentration (MIC) value of 1.95μg/mL) against Staphylococcus aureus and the most active antifungal agent (with an MIC value of 3.90μg/mL) against Candida albicans, Aspergillus niger, and Rhizopus nigricans.

Linking quinoline ring to 5-nitrofuran moiety via sulfonyl hydrazone bridge: Synthesis, structural characterization, DFT studies, and evaluation of antibacterial and antifungal activity

In the present work, we report the synthesis, structural characterization, and computational studies of (E)-N'-((5-nitrofuran-2-yl)methylene)quinoline-8-sulfonohydrazide (QNF) as a potential antimicrobial drug candidate. To design the target molecule, we utilized a molecular hybridization technique that connects two antimicrobial pharmacophores (quinoline and 5-nitrofuran rings) with a sulfonyl hydrazone moiety. QNF was synthesized by the condensation of quinoline-8-sulfonohydrazide with 5-nitrofuran-2-carbaldehyde, and characterized by various spectral techniques including single-crystal X-ray crystallography. QNF was extensively evaluated for its antibacterial and antifungal activity. The inhibition capacity of QNF on Candida albicans filamentation and biofilm formation was further investigated. Biofilm inhibition of QNF against C. albicans was supported by molecular docking studies in the binding site of agglutinin-like sequence 3 (Als3). Drug-like profile of QNF was confirmed by in silico calculation of its significant physicochemical properties. Additionally, the optimized geometrical structure, natural bond orbital calculations, frontier molecular orbital and molecular electrostatic potential analysis of QNF were carried out using the density functional theory method at the B3LYP with 6–31+G(d,p) basis set. The predictions of 1H and 13C NMR chemical shift values were performed using the gauge-independent atomic orbital method. Structural parameters and NMR values obtained experimentally were compared with the calculated values.

Unraveling Membrane-Disruptive Properties of Sodium Lauroyl Lactylate and Its Hydrolytic Products: A QCM-D and EIS Study.

Membrane-disrupting lactylates are an important class of surfactant molecules that are esterified adducts of fatty acid and lactic acid and possess industrially attractive properties, such as high antimicrobial potency and hydrophilicity. Compared with antimicrobial lipids such as free fatty acids and monoglycerides, the membrane-disruptive properties of lactylates have been scarcely investigated from a biophysical perspective, and addressing this gap is important to build a molecular-level understanding of how lactylates work. Herein, using the quartz crystal microbalance-dissipation (QCM-D) and electrochemical impedance spectroscopy (EIS) techniques, we investigated the real-time, membrane-disruptive interactions between sodium lauroyl lactylate (SLL)-a promising lactylate with a 12-carbon-long, saturated hydrocarbon chain-and supported lipid bilayer (SLB) and tethered bilayer lipid membrane (tBLM) platforms. For comparison, hydrolytic products of SLL that may be generated in biological environments, i.e., lauric acid (LA) and lactic acid (LacA), were also tested individually and as a mixture, along with a structurally related surfactant (sodium dodecyl sulfate, SDS). While SLL, LA, and SDS all had equivalent chain properties and critical micelle concentration (CMC) values, our findings reveal that SLL exhibits distinct membrane-disruptive properties that lie in between the rapid, complete solubilizing activity of SDS and the more modest disruptive properties of LA. Interestingly, the hydrolytic products of SLL, i.e., the LA + LacA mixture, induced a greater degree of transient, reversible membrane morphological changes but ultimately less permanent membrane disruption than SLL. These molecular-level insights support that careful tuning of antimicrobial lipid headgroup properties can modulate the spectrum of membrane-disruptive interactions, offering a pathway to design surfactants with tailored biodegradation profiles and reinforcing that SLL has attractive biophysical merits as a membrane-disrupting antimicrobial drug candidate.

Enzymatic Synthesis of a Novel Coumarin Aminophosphonates: Antibacterial Effects and Oxidative Stress Modulation on Selected E. coli Strains.

The objective of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity toward selected LPS-varied E. coli strains. Studied antimicrobial agents were prepared via a Kabachnik-Fields reaction promoted by lipases. The products were provided with an excellent yield (up to 92%) under mild, solvent- and metal-free conditions. A preliminary exploration of coumarin α-amino dimethyl phosphonate analogs as novel antimicrobial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The structure-activity relationship revealed that an inhibitory activity of the synthesized compounds is strongly related to the type of the substituents located in the phenyl ring. The collected data demonstrated that coumarin-based α-aminophosphonates can be potential antimicrobial drug candidates, which is particularly crucial due to the constantly increasing resistance of bacteria to commonly used antibiotics.

Evaluation of some o-benzenedisulfonimido–sulfonamide derivatives as potent antimicrobial agents

Background and Aims: The discovery of new antimicrobials to overcome antimicrobial resistance has always been an important topic for sustainable world health. Since the sulfonamide carrying heterocyclic compounds present a number of advantages as biologically active compounds, in our work reported herein, a small collection of previously synthesized o-benzenedisulfonimido-sulfonamide derivatives were assayed to determine antimicrobial profiles against ten different microorganisms in search of finding promising new antibacterial/antifungal agents. Methods: Eight compounds and their standards were tested against seven bacterial and three fungal strains, including members of Gram-positive, Gram-negative bacteria, and Candida spp., using the microbroth dilution method to measure their MIC (minimum inhibitory concentration) values. Results: All assayed molecules showed different inhibitory effects on ten different targets, with considerable MIC values. Particularly, compound 2 exhibited better antimicrobial activity against the largest number of assayed microorganisms. Conclusion: Further modification and development of o-benzenedisulfonimido-sulfonamide derivatives and additional in vitro studies against putative targets may result in new antimicrobial drug candidates in the near future.

Metabolic and Transcriptional Stress Memory in Sorbus pohuashanensis Suspension Cells Induced by Yeast Extract

Plant stress memory can provide the benefits of enhanced protection against additional stress exposure. Here, we aimed to explore the responses of recurrent and non-recurrent yeast extract (YE) stresses in Sorbus pohuashanensis suspension cells (SPSCs) at metabolomics and transcriptional levels. Biochemical analyses showed that the cell wall integrity and antioxidation capacity of SPSCs in the pretreated group were evidently improved. Metabolic analysis showed that there were 39 significantly altered metabolites in the pretreated group compared to the non-pretreated group. Based on the transcriptome analysis, 219 differentially expressed genes were obtained, which were highly enriched in plant-pathogen interaction, circadian rhythm-plant, oxidative phosphorylation, and phenylpropanoid biosynthesis. Furthermore, the correlation analysis of the transcriptome and metabolome data revealed that phenylpropanoid biosynthesis involved in the production of biphenyl phytoalexins may play a critical role in the memory response of SPSC to YE, and the key memory genes were also identified, including PAL1, BIS1, and BIS3. Collectively, the above results demonstrated that the memory responses of SPSC to YE were significant in almost all levels, which would be helpful for better understanding the adaptation mechanisms of medicinal plants in response to biotic stress, and laid a biotechnological foundation to accumulate favorable antimicrobial drug candidates from plant suspension cells.

Synthesis, molecular docking, ADME study, and antimicrobial potency of piperazine based cinnamic acid bearing coumarin moieties as a DNA gyrase inhibitor.

A series of novel piperazine based cinnamic acid bearing coumarin derivatives were designed and synthesized by piperazine based cinnamic acids esterification with 4-hydroxycoumarin and characterized by various spectral techniques like infrared, 1 H nuclear magnetic resonance (NMR), 13 C NMR, and mass. The novel bioactive compounds (7a-7m) screen their potential against different bacterial and fungal strains. Compound 7g (minimum inhibitory concentration [MIC] = 12.5 µg/ml) exhibited potent antibacterial activity against Escherichia colistrain. Compounds 7d, 7f, 7g, 7k, 7l, and 7m showed potent antibacterial activity against all bacterial strains. Compounds 7a, 7g, 7h, 7k, 7l, and 7m exhibited potent antifungal activity against all fungal strains. Furthermore, a molecular docking study revealed that compounds 7d, 7f, 7g, and 7k could bind to the active site of E. coli DNA gyrase subunit B protein and form hydrogen bonding with crucial amino acid residues Arg136 in the active sites. Comprehensively, our study recommends that 7d, 7f, 7g, and 7k could be a promising lead for developing more efficient antimicrobial drug candidates and DNA gyrase inhibitors.

Synthesis, antimicrobial properties and in silico studies of aryloxyacetic acid derivatives with hydrazone or thiazolidine-4-one scaffold

In this work, twenty hydrazide-hydrazone and 4-thiazolidinone derivatives were synthesized starting from m-cresol. Antimicrobial evaluation was carried out by microdilution method against Enterococcus faecalis and Staphylococcus aureus as Gram-positive bacteria and Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria, and three pathogenic fungi Candida albicans, Candida parapsilosis and Candida krusei. Some compounds possessed considerable antimicrobial properties against the tested microorganisms, particularly against E. coli. 4-Thiazolidinones containing 3-methoxyphenyl and 3,5-dichlorophenyl moieties (4h and 4i) were found to be the most active derivatives with MICs of 2 μg/mL against E. coli. N'-[(3,5-dichlorophenyl)methylidene]-2-(3-methylphenoxy)acetohydrazide (3i) also displayed antifungal activity against Candida krusei that was comparable to fluconazole. Calculated drug-likeness and ADMET parameters of the most active compounds confirmed their potential as antimicrobial drug candidates. Molecular docking investigations were carried out in the thiamine diphosphate-binding site of pyruvate dehydrogenase multienzyme complex E1 component (PDHc-E1) to clarify the potential antibacterial mechanism against E. coli. The results showed the potential and importance of developing new hydrazones and 4-thiazolidinones that would be effective against microbial strains. Communicated by Ramaswamy H. Sarma

Discovery of quinolinequinones with N-phenylpiperazine by conversion of hydroxyquinoline as a new class of antimicrobial agents targeting resistant pathogenic microorganisms

The development of new antimicrobial agents is necessary to overcome the emerging antimicrobial resistance among infectious microbial pathogens. Herein, we successfully designed and synthesized quinolinequinones (QQs) with N-phenylpiperazine (QQ1-7) containing strong or weak EDG in the amino moiety by converting hydroxyquinoline (HQ) to the dichloroquinolinequinone (QQ) via chlorooxidation. We performed an extensive antimicrobial activity assessment of the QQs with N-phenylpiperazine (QQ1-7). Among the seven quinolinequinones (QQs) with N-phenylpiperazine tested, QQ3 and QQ4 were the most active molecules against Staphylococcus aureus (ATCC® 29213) with a MIC value of 1.22 μg/mL. In addition to this, while QQ4 was more than six (6) times more effective towards Enterococcus faecalis (ATCC® 29212), QQ3 was twenty-six (26) times more effective against same strain. Furthermore, the evaluation of antimicrobial activity indicated that six of seven synthesized QQs (QQ1-4, QQ6, and QQ7) exhibited superior biological potency, eight (8) times for five of them (QQ1-4 and QQ6) and two (2) times for QQ7, against Staphylococcus epidermidis (ATCC® 12228). Besides, all QQs except QQ5 displayed excellent antifungal activity against the fungi Candida albicans (ATCC® 10231). Among these, the two QQs (QQ3 and QQ4), which showed the lowest values against gram-positive bacterial strains (Staphylococcus aureus (ATCC® 29213), Staphylococcus epidermidis (ATCC® 12228), and Enterococcus faecalis (ATCC® 29212)) as well as fungal strains (Candida albicans (ATCC® 10231) and Candida parapsilosis (ATCC® 22019)), were further evaluated for their biofilm inhibition properties and their mode of action with in vitro potential antimicrobial activity against each of 20 clinically obtained resistant strains of gram-positive bacteria, and bactericidal activity using time-kill curve assay. In this study, we investigated the bactericidal effects of QQ3 against methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans strains. The findings of this study suggest that a significant bactericidal effect was seen with all tested 1 × MIC and 4 × MIC concentrations used within 24 h. Our findings present significant implications for an antimicrobial drug candidate for treating infections, especially those caused by clinically resistant MRSA isolates.

Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has led to serious infections, especially in hospitals and clinics, where treatment and prevention have become more difficult due to the formation of biofilms. Owing to biofilm-derived antibiotic tolerance, the currently available traditional antibiotics have failed to treat MRSA infections. Hence, there is a urgent need to develop novel antibiotics for treating life-threatening MRSA infections. Lugdunin (cyclic peptide-1), a nonribosomal cyclic peptide produced by Staphylococcus lugdunensis, exhibits potent antimicrobial activity against MRSA. Amazingly, cyclic peptide-1 and its analogues cyclic peptide-11 and cyclic peptide-14 have the ability to disperse mature MRSA biofilms and show anti-clinical MRSA activity, including MRSA persister cells. In addition, these three cyclic peptide compounds have non-toxicity, lower hemolytic activity and lack of resistance development. Our results indicate that cyclic peptide-1, cyclic peptide-11, and cyclic peptide-14 have great potential as new antimicrobial drug candidates for the treatment of clinical MRSA infections.

Synthesis and biological evaluation of fluoro-substituted cationic and neutral antibiotic NHC* silver derivatives of SBC3

Two fluoro-substituted neutral carbene silver acetates and thirteen cationic dicarbene silver complexes were synthesised from the appropriate imidazolium precursors in good to very good yields using batch and flow synthesis. Six of the derivatives were characterised by XRD and showed expected structural aspects in the solid state. Most of these fifteen new silver-based antimicrobial drug candidates showed improved stability as well as comparable biological activity against E. coli and Methicillin-resistant S. aureus when compared against the lead compound 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene silver(I) acetate (SBC3). Fluoro-substitution as well as the use of dicarbene complexes have the potential to develop the field of silver-based antimicrobials further.

Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies.

Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources.

Optimization of the antimicrobial peptide Bac7 by deep mutational scanning

BackgroundIntracellularly active antimicrobial peptides are promising candidates for the development of antibiotics for human applications. However, drug development using peptides is challenging as, owing to their large size, an enormous sequence space is spanned. We built a high-throughput platform that incorporates rapid investigation of the sequence-activity relationship of peptides and enables rational optimization of their antimicrobial activity. The platform is based on deep mutational scanning of DNA-encoded peptides and employs highly parallelized bacterial self-screening coupled to next-generation sequencing as a readout for their antimicrobial activity. As a target, we used Bac71-23, a 23 amino acid residues long variant of bactenecin-7, a potent translational inhibitor and one of the best researched proline-rich antimicrobial peptides.ResultsUsing the platform, we simultaneously determined the antimicrobial activity of >600,000 Bac71-23 variants and explored their sequence-activity relationship. This dataset guided the design of a focused library of ~160,000 variants and the identification of a lead candidate Bac7PS. Bac7PS showed high activity against multidrug-resistant clinical isolates of E. coli, and its activity was less dependent on SbmA, a transporter commonly used by proline-rich antimicrobial peptides to reach the cytosol and then inhibit translation. Furthermore, Bac7PS displayed strong ribosomal inhibition and low toxicity against eukaryotic cells and demonstrated good efficacy in a murine septicemia model induced by E. coli.ConclusionWe demonstrated that the presented platform can be used to establish the sequence-activity relationship of antimicrobial peptides, and showed its usefulness for hit-to-lead identification and optimization of antimicrobial drug candidates.

Design, synthesis, in vitro and in silico bioactivity profiles of new urea/thiourea derivatives of 2-pyridyl piperazine as potent antioxidant and antimicrobial agents: chemo-bio-computational approach

Synthesis of a series of new urea and thiourea derivatives of 2-pyridyl piperazine was accomplished by reacting various isocyanates and isothiocyanates in the presence of triethylamine (TEA) at 50 °C. All the title compounds were obtained in high yields and their structures were characterized by IR, 1H, 13C NMR, Mass spectral, and Elemental analysis. The synthesized compounds were screened for in vitro and in silico antioxidant and antimicrobial activities. All the title compounds exhibited potent antioxidant and antimicrobial activities. Out of all, 2c and 2f against DPPH, H2O2 and Nitro oxide have exhibited significant activity and the levels of activity were higher than the reference compounds, ascorbic acid and BHT. Whereas 2a, 2c, 2f and 2j have shown prominent activity in terms of zone of inhibition against all the microbial strains tested than the standards such as levofloxacin and nystatin. In addition in silico studies also conveyed the same that is 2a, 2c, 2f and 2j have displayed the highest binding energies against peroxiredoxins and DNA gyrase protein than the standards akin to the rest of the compounds. In overall, 2c and 2f have exhibited most promising antioxidant and antimicrobial activity than the rest of the title compounds in vitro and in silico. Hence, 2c and 2f will stand as a lead and promising antioxidant and antimicrobial drug candidates in future. Communicated by Ramaswamy H. Sarma

A Facile Synthesis of New Substituted Thiazol-2-amine Derivatives as Potent Antimicrobial Agent

A facile synthesis of a new thiazol-2-amine derivative as antimicrobial agent and condensation with substituted thiourea compounds to afford the corresponding substituted thiazole derivatives in excellent yields. All the reactions were completed within less reaction time at reflux temperature. According to the result obtained, the compounds 3b, 3d, 3e, 3f, 3g, 3i, 3l, and 3m were found the leader antimicrobial activity with the highest MIC values. The synthesized compound can be considered to develop new antimicrobial drug candidates. Amongst these, many compounds show better antibacterial and antifungal activity. The compounds 3b, 3d, 3e, 3l, and 3m exhibited significant antibacterial activity against B. subtilis, S. aureus, and E. coli. The compounds 3f, 3g, 3i show significant antifungal against fungal strains i.e., C. albicans, A. flavus and A. niger.

2-(4-nitrophenyl)iminomethyl phenol Schiff base metal complexes: Synthesis, spectroscopic characterization, anticancer and antimicrobial studies

An imine-based molecule, 2-(4-nitrophenyl)iminomethyl phenol Schiff base (NPIMP) ligand was synthesized by microwave and conventional methods by reaction between 4-nitroaniline (1) and salicyaldehyde (2). The metal complexes of La(III), Co(II), Ni(II) and Cu(II) (3a-d) with NPIMP were synthesized as potential anticancer and antimicrobial drug candidates. The synthesized ligand and metal complexes were structurally characterized by spectral (NMR, FT-IR, LC-MS and UV-Vis), scanning electron microscopy, elemental analysis, powder X-ray diffraction and thermo gravimetric (TG) data. Spectroscopic studies suggested a distorted octahedral structure for all the complexes. The systems were evaluated for their anticancer and antimicrobial activities. The anticancer activity studies revealed that all the complexes exhibited promising activity against MCF-7 breast and HeLa cell lines. Antimicrobial activity has shown that all the complexes were showed certain degree of activity. As for the antimicrobial activity, La(III) and Co(II) complexes displayed potential antibacterial and antifungal activity against the tested microbes.