Results of a large-scale screening programme to detect antibacterial activity from freshwater algae

This report deals with an effort to begin the process of effectively identifying children in rural areas with speech and language problems using existing school personnel. A two-day competency-based workshop for the purpose of training aides to conduct a large-scale screening of speech and language problems in elementary-school-age children is described. Training strategies, implementation, and evaluation procedures are discussed.

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Green synthesis, characterization of silver sulfide nanoparticles and antibacterial activity evaluation

10.31221/osf.io/8byuc ◽

2019 ◽

Author(s):

Chem Int

Keyword(s):

Antibacterial Activity ◽

Large Scale ◽

Research Work ◽

Silver Sulfide ◽

Morphological Properties ◽

Effective Diameter ◽

Novel Approach ◽

Transmission Electron ◽

Green Route ◽

Silver Sulfide Nanoparticles

This research work presents a facile and green route for synthesis silver sulfide (Ag2SNPs) nanoparticles from silver nitrate (AgNO3) and sodium sulfide nonahydrate (Na2S.9H2O) in the presence of rosemary leaves aqueous extract at ambient temperature (27 oC). Structural and morphological properties of Ag2SNPs nanoparticles were analyzed by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The surface Plasmon resonance for Ag2SNPs was obtained around 355 nm. Ag2SNPs was spherical in shape with an effective diameter size of 14 nm. Our novel approach represents a promising and effective method to large scale synthesis of eco-friendly antibacterial activity silver sulfide nanoparticles.

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Identification of N-Substituted Triazolo-azetidines as Novel Antibacterials using pDualrep2 HTS Platform

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190412165316 ◽

2019 ◽

Vol 22 (5) ◽

pp. 346-354

Author(s):

Yan A. Ivanenkov ◽

Renat S. Yamidanov ◽

Ilya A. Osterman ◽

Petr V. Sergiev ◽

Vladimir A. Aladinskiy ◽

...

Keyword(s):

Antibacterial Activity ◽

Large Scale ◽

Underlying Mechanism ◽

Luciferase Assay ◽

Reporter System ◽

E Coli ◽

Starting Point ◽

High Concentrations ◽

Mic Value

Aim and Objective: Antibiotic resistance is a serious constraint to the development of new effective antibacterials. Therefore, the discovery of the new antibacterials remains one of the main challenges in modern medicinal chemistry. This study was undertaken to identify novel molecules with antibacterial activity. Materials and Methods: Using our unique double-reporter system, in-house large-scale HTS campaign was conducted for the identification of antibacterial potency of small-molecule compounds. The construction allows us to visually assess the underlying mechanism of action. After the initial HTS and rescreen procedure, luciferase assay, C14-test, determination of MIC value and PrestoBlue test were carried out. Results: HTS rounds and rescreen campaign have revealed the antibacterial activity of a series of Nsubstituted triazolo-azetidines and their isosteric derivatives that has not been reported previously. Primary hit-molecule demonstrated a MIC value of 12.5 µg/mL against E. coli Δ tolC with signs of translation blockage and no SOS-response. Translation inhibition (26%, luciferase assay) was achieved at high concentrations up to 160 µg/mL, while no activity was found using C14-test. The compound did not demonstrate cytotoxicity in the PrestoBlue assay against a panel of eukaryotic cells. Within a series of direct structural analogues bearing the same or bioisosteric scaffold, compound 2 was found to have an improved antibacterial potency (MIC=6.25 µg/mL) close to Erythromycin (MIC=2.5-5 µg/mL) against the same strain. In contrast to the parent hit, this compound was more active and selective, and provided a robust IP position. Conclusion: N-substituted triazolo-azetidine scaffold may be used as a versatile starting point for the development of novel active and selective antibacterial compounds.

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Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666190122151634 ◽

2019 ◽

Vol 19 (1) ◽

pp. 4-16 ◽

Cited By ~ 6

Author(s):

Qihui Wu ◽

Hanzhong Ke ◽

Dongli Li ◽

Qi Wang ◽

Jiansong Fang ◽

...

Keyword(s):

Machine Learning ◽

Drug Discovery ◽

Large Scale ◽

Recent Progress ◽

High Specificity ◽

Learning Approaches ◽

Anticancer Peptides ◽

The Past ◽

Traditional Approaches ◽

Large Scale Screening

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

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Large-scale High-throughput Screening Revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as Novel Template for Antibacterial Agents

Current Drug Discovery Technologies ◽

10.2174/1570163816666190603095521 ◽

2020 ◽

Vol 17 (5) ◽

pp. 716-724

Author(s):

Yan A. Ivanenkov ◽

Renat S. Yamidanov ◽

Ilya A. Osterman ◽

Petr V. Sergiev ◽

Vladimir A. Aladinskiy ◽

...

Keyword(s):

Antibacterial Activity ◽

High Throughput ◽

High Throughput Screening ◽

Large Scale ◽

Antibacterial Agents ◽

Sos Response ◽

Luciferase Assay ◽

Translational Machinery ◽

E Coli ◽

New Class

Background: The key issue in the development of novel antimicrobials is a rapid expansion of new bacterial strains resistant to current antibiotics. Indeed, World Health Organization has reported that bacteria commonly causing infections in hospitals and in the community, e.g. E. Coli, K. pneumoniae and S. aureus, have high resistance vs the last generations of cephalosporins, carbapenems and fluoroquinolones. During the past decades, only few successful efforts to develop and launch new antibacterial medications have been performed. This study aims to identify new class of antibacterial agents using novel high-throughput screening technique. Methods: We have designed library containing 125K compounds not similar in structure (Tanimoto coeff.< 0.7) to that published previously as antibiotics. The HTS platform based on double reporter system pDualrep2 was used to distinguish between molecules able to block translational machinery or induce SOS-response in a model E. coli system. MICs for most active chemicals in LB and M9 medium were determined using broth microdilution assay. Results: In an attempt to discover novel classes of antibacterials, we performed HTS of a large-scale small molecule library using our unique screening platform. This approach permitted us to quickly and robustly evaluate a lot of compounds as well as to determine the mechanism of action in the case of compounds being either translational machinery inhibitors or DNA-damaging agents/replication blockers. HTS has resulted in several new structural classes of molecules exhibiting an attractive antibacterial activity. Herein, we report as promising antibacterials. Two most active compounds from this series showed MIC value of 1.2 (5) and 1.8 μg/mL (6) and good selectivity index. Compound 6 caused RFP induction and low SOS response. In vitro luciferase assay has revealed that it is able to slightly inhibit protein biosynthesis. Compound 5 was tested on several archival strains and exhibited slight activity against gram-negative bacteria and outstanding activity against S. aureus. The key structural requirements for antibacterial potency were also explored. We found, that the unsubstituted carboxylic group is crucial for antibacterial activity as well as the presence of bulky hydrophobic substituents at phenyl fragment. Conclusion: The obtained results provide a solid background for further characterization of the 5'- (carbonylamino)-2,3'-bithiophene-4'-carboxylate derivatives discussed herein as new class of antibacterials and their optimization campaign.

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Analytical Validation and Clinical Application of Rapid Serological Tests for SARS-CoV-2 Suitable for Large-Scale Screening

Diagnostics ◽

10.3390/diagnostics11050869 ◽

2021 ◽

Vol 11 (5) ◽

pp. 869

Author(s):

Amedeo De Nicolò ◽

Valeria Avataneo ◽

Jessica Cusato ◽

Alice Palermiti ◽

Jacopo Mula ◽

...

Keyword(s):

Early Diagnosis ◽

Real Time Pcr ◽

Large Scale ◽

High Sensitivity ◽

Analytical Validation ◽

Pcr Assay ◽

Serological Tests ◽

Flow Test ◽

Lateral Flow Test ◽

Large Scale Screening

Recently, large-scale screening for COVID-19 has presented a major challenge, limiting timely countermeasures. Therefore, the application of suitable rapid serological tests could provide useful information, however, little evidence regarding their robustness is currently available. In this work, we evaluated and compared the analytical performance of a rapid lateral-flow test (LFA) and a fast semiquantitative fluorescent immunoassay (FIA) for anti-nucleocapsid (anti-NC) antibodies, with the reverse transcriptase real-time PCR assay as the reference. In 222 patients, LFA showed poor sensitivity (55.9%) within two weeks from PCR, while later testing was more reliable (sensitivity of 85.7% and specificity of 93.1%). Moreover, in a subset of 100 patients, FIA showed high sensitivity (89.1%) and specificity (94.1%) after two weeks from PCR. The coupled application for the screening of 183 patients showed satisfactory concordance (K = 0.858). In conclusion, rapid serological tests were largely not useful for early diagnosis, but they showed good performance in later stages of infection. These could be useful for back-tracing and/or to identify potentially immune subjects.

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