scholarly journals Search for hits and early leads from soil bacteria to combat infectious diseases

2018 ◽  
Vol 12 (02.1) ◽  
pp. 24S
Author(s):  
Jennifer Herrmann
Keyword(s):  
Natural Products ◽  
Soil Bacteria ◽  
Antimicrobial Agents ◽  
State Of The Art ◽  
Large Fraction ◽  
Analytical Techniques ◽  
Gram Negative Bacteria ◽  
Topoisomerase Inhibitors ◽  
Antimicrobial Compound ◽  
Cellular Targets

Introduction: Natural products are the source of a large fraction of the current pharmaceutics available against human disease. However, the discovery of novel compounds with new mechanisms of action is becoming increasingly challenging. We focused our work on soil-dwelling Myxobacteria from highly diverse samples, which are more and more recognized as an important natural product source. Methodology: Our discovery pipeline combines traditional whole cell-based activity screens with state-of-the-art analytical techniques and a comprehensive dereplication process. Having identified an antimicrobial compound we aim at elucidating its target, MOA and MOR in diverse microbiological screens and by applying ‘omic’ technologies. Results: Two case studies of currently investigated compound classes will be highlighted. Cystobactamids are novel topoisomerase inhibitors that display very pronounced activity on Gram-positive and Gram-negative bacteria. Telomycins from Streptomyces canus bind to cardiolipin and our studies revealed other putative cellular targets. Conclusion: We were able to isolate several new natural products with potent and selective activity against clinically relevant pathogens. Interestingly, underlying MOAs often differ from those of already described antimicrobial agents.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals Super-Cationic Peptide Dendrimers—Synthesis and Evaluation as Antimicrobial Agents

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 695
Author(s):  
Estelle J. Ramchuran ◽  
Isabel Pérez-Guillén ◽  
Linda A. Bester ◽  
René Khan ◽  
Fernando Albericio ◽  
...  
Keyword(s):  
Antibacterial Agent ◽  
Antimicrobial Agents ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Cationic Peptide ◽  
Public Health Concern ◽  
Gram Negative ◽  
Peptide Dendrimers ◽  
Microbial Infections ◽  
Lead Candidate

Microbial infections are a major public health concern. Antimicrobial peptides (AMPs) have been demonstrated to be a plausible alternative to the current arsenal of drugs that has become inefficient due to multidrug resistance. Herein we describe a new AMP family, namely the super-cationic peptide dendrimers (SCPDs). Although all members of the series exert some antibacterial activity, we propose that special attention should be given to (KLK)2KLLKLL-NH2 (G1KLK-L2KL2), which shows selectivity for Gram-negative bacteria and virtually no cytotoxicity in HepG2 and HEK293. These results reinforce the validity of the SCPD family as a valuable class of AMP and support G1KLK-L2KL2 as a strong lead candidate for the future development of an antibacterial agent against Gram-negative bacteria.

Newer Quinolones in the Treatment of Continuous Ambulatory Peritoneal Dialysis (CAPD) Related Infections

1990 ◽  
Vol 10 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Paul Nikolaidis
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Adverse Reactions ◽  
Antimicrobial Agents ◽  
Hospital Staff ◽  
Gram Negative Bacteria ◽  
Promising Alternative ◽  
Gram Negative ◽  
Dosing Intervals ◽  
Good Oral Bioavailability

Newer fluoroquinolones such as ciprofloxacin, pefloxacin, ofloxacin, enoxacin, and fleroxacin are potent antimicrobial agents against many gram-negative bacteria, including Pseudomonas aeruginosa species and staphylococci-sensitive or resistant to methicillin. They are almost completely absorbed when given orally, reaching therapeutic plasma and dialysate concentrations, and their long half lives permit infrequent dosing intervals. Clinical studies on fluoroquinolones efficacy in continuous ambulatory peritoneal dialysis (CAPD) infections, although not extensive, demonstrate good results. They are well tolerated and the adverse reactions, consisting mainly of gastrointestinal disturbance, were uncommon, mild, and reversible. The fluoroquinolones offer a promising alternative to standard parenteral treatments in CAPD patients, while their good oral bioavailability makes them attractive and convenient for both patients and hospital staff. However, they must be used with caution until we have more information and gain further experience.

scholarly journals OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shira Mandel ◽  
Janna Michaeli ◽  
Noa Nur ◽  
Isabelle Erbetti ◽  
Jonathan Zazoun ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Safety Margin ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

Natural products targeting cancer stem cells: a revisit

2021 ◽  
Vol 28 ◽  
Author(s):  
Jiahua Cui ◽  
Jiajun Qian ◽  
Larry Ming-Cheung Chow ◽  
Jinping Jia
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Therapeutic Potential ◽  
Tumor Development ◽  
Biologically Active ◽  
Cellular Targets ◽  
Drug Candidates ◽  
Enhanced Expression

Background: The proposed central role of cancer stem cells (CSCs) in tumor development has been extended to explain the diverse oncologic phenomena such as multidrug resistance, metastasis and tumor recurrence in clinics. Due to the enhanced expression of ATP-binding cassette transporters and anti-apoptotic factors, stagnation on G0 phase and the strong ability of self-renewal, the CSCs were highly resistant to clinical anticancer drugs. Therefore, the discovery of new drug candidates that could effectively eradicate cancer stem cells afforded promising outcomes in cancer therapy. Introduction: Natural products and their synthetic analogues are a rich source of biologically active compounds and several of them have already been recognized as potent CSCs killers. We aim to provide a collection of recently identified natural products that suppressed the survival of the small invasive CSC populations and combated the drug resistance of these cells in chemotherapy. Results and Conclusion: These anti-CSCs natural products included flavonoids, stilbenes, quinones, terpenoids, polyketide antibiotics, steroids and alkaloids. In the present review, we highlighted the therapeutic potential of natural products and their derivatives against the proliferation and drug resistance of CSCs, their working mechanisms and related structure-activity relationships. Meanwhile, in this survey, several natural products with diverse cellular targets such as the naphthoquinone shikonin and the stilbene resveratrol were characterized as promising lead compounds for future development.

Identifying the cellular targets of natural products using T7 phage display

2016 ◽  
Vol 33 (5) ◽  
pp. 626-636 ◽  
Author(s):  
Andrew M. Piggott ◽  
Peter Karuso
Keyword(s):  
Natural Products ◽  
Phage Display ◽  
Chemistry Laboratory ◽  
Cellular Targets ◽  
T7 Phage Display ◽  
T7 Phage

A description of the T7 phage biopanning procedure is provided with tips and advice suitable for setup in a chemistry laboratory.

scholarly journals ISOLASI DAN PENENTUAN INDEKSHIDROLISIS BAKTERI AMILOLITIK DARI TANAH SEDIMENT MANGROVE DI WONOREJO, SURABAYA

2019 ◽  
Vol 10 (1) ◽  
pp. 38
Author(s):  
Aliyah Siti Sundari ◽  
Ni Nyoman Purwani ◽  
Anita Kurniati
Keyword(s):  
Soil Bacteria ◽  
Mangrove Ecosystem ◽  
Soil Characteristics ◽  
Mangrove Sediment ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Lugol’S Iodine ◽  
Gram Staining ◽  
Special Soil

Mangrove sediment is a habitat for various bacteria, one of them is amylolytic bacteria which has the potential to produce amylase enzyme. Amylase enzyme has many benefits in industry, textiles and medical. The mangrove ecosystem area has special soil characteristics, which have the opportunity to have microorganism diversity, one of which is the mangrove ecosystem in the Wonorejo region, Surabaya. This study aims to obtain potential amylolytic bacteria from potential amylolytic isolates derived from mangrove sediment. Soil bacteria were isolated in Starch media for 2% agar and tested with Lugol’s Iodine reagents to measure their amylolytic index. Character isolates observed included colony morphology, Gram staining, and motility. Of the 27 isolates found there were 3 isolates with the highest index values in their activity, namely isolates A.7, A.27 and A.64. Characterization results showed that isolates A.7 and A.64 were Gram negative bacteria, and isolates A.27 were Gram positive bacteria. And the motility results for the three isolates were negative, with the results of a positive catalase test.

scholarly journals Synergistic effects of natural products and commercial antibiotics

2020 ◽  
Author(s):  
Lucia Nitsch-Velasquez
Keyword(s):  
Natural Products ◽  
Synergistic Effects ◽  
Gram Negative Bacteria ◽  
Polar Solvents ◽  
Microbial Strains ◽  
Polar Extracts ◽  
Review Reports ◽  
New Treatments ◽  
Discovery Pipeline

Context: The antimicrobial resistant era requires advances in the approaches and technologies to find new treatments. The enhancement of the antimicrobial activity of commercially available drugs (CADs) by natural products (NPs) has successful mixtures (e.g., clavulanic acid and amoxicillin). Objective: To systematically review reports of synergistic effects of CADs and NPs against opportunistic microbial strains from 2010 to April 2016. Methods: The databases and search engines PubMed, Medline, Scifinder, Scopus, ScienceDirect, Scholar Google were systematically searched. Among the keywords utilized were: synergistic effects natural products and antibioitcs, botanicals and antibiotics bioassays, plant extracts interaction with antibioitics and antibiotic adjuvant bioassays. Only synergistic results were tabulated and analyzed according to CADs, NPs and strains. Results: A set of 76 studies that reported in vitro synergistic effects of CADs and NPs against gram−positive or gram−negative bacteria or fungi opportunistic strains was found. From the 60 reports on antibacterial adjuvants, the most frequent designs involved beta−lactamics or aminoglycosides against Methicillin Resistant Staphylococcus aureus. The assayed NPs encompassed extracts or fractions from 22 different species distributed worldwide (45% extracted with non−polar solvents) and 33 purified compounds (flavonoids, other polyphenols and alkaloids). Conclusions: NPs as potential drug hits for antimicrobial adjuvants had been found and should continue in the drug discovery pipeline. The field certainly would benefit of advances in purification technologies, especially for polar extracts and bioassay platforms.

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