scholarly journals The Design of Alapropoginine, a Novel Conjugated Ultrashort Antimicrobial Peptide with Potent Synergistic Antimicrobial Activity in Combination with Conventional Antibiotics

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 712
Author(s):  
Ali Salama ◽  
Ammar Almaaytah ◽  
Rula M. Darwish
Keyword(s):  
Antimicrobial Activity ◽  
Hemolytic Activity ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Resistant Bacteria ◽  
Human Red Blood Cells ◽  
Drug Resistant Bacteria ◽  
Different Strains ◽  
Conventional Antibiotics

(1) Background: Antimicrobial resistance represents an urgent health dilemma facing the global human population. The development of novel antimicrobial agents is needed to face the rising number of resistant bacteria. Ultrashort antimicrobial peptides (USAMPs) are considered promising antimicrobial agents that meet the required criteria of novel antimicrobial drug development. (2) Methods: Alapropoginine was rationally designed by incorporating arginine (R), biphenylalanine (B), and naproxen to create an ultrashort hexapeptide. The antimicrobial activity of alapropoginine was evaluated against different strains of bacteria. The hemolytic activity of alapropoginine was also investigated against human erythrocytes. Finally, synergistic studies with antibiotics were performed using the checkerboard technique and the determination of the fractional inhibitory index. (3) Results: Alapropoginine displayed potent antimicrobial activities against reference and multi-drug-resistant bacteria with MIC values of as low as 28.6 µg/mL against methicillin-resistant S. aureus. Alapropoginine caused negligible toxicity toward human red blood cells. Moreover, the synergistic studies showed improved activities for the combined conventional antibiotics with a huge reduction in their antimicrobial concentrations. (4) Conclusions: The present study indicates that alapropoginine exhibits promising antimicrobial activity against reference and resistant strains of bacteria with negligible hemolytic activity. Additionally, the peptide displays synergistic or additive effects when combined with several antibiotics.

scholarly journals Potential of Novel Antimicrobial Peptide P3 from Bovine Erythrocytes and Its Analogs To Disrupt Bacterial MembranesIn Vitroand Display Activity against Drug-Resistant Bacteria in a Mouse Model

2015 ◽  
Vol 59 (5) ◽  
pp. 2835-2841 ◽  
Author(s):  
Qinghua Zhang ◽  
Yanzhao Xu ◽  
Qing Wang ◽  
Bolin Hang ◽  
Yawei Sun ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Body Weight ◽  
Mouse Model ◽  
Antimicrobial Activities ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Resistant Strains ◽  
Bovine Erythrocytes

ABSTRACTWith the emergence of many antibiotic-resistant strains worldwide, antimicrobial peptides (AMPs) are being evaluated as promising alternatives to conventional antibiotics. P3, a novel hemoglobin peptide derived from bovine erythrocytes, exhibited modest antimicrobial activityin vitro. We evaluated the antimicrobial activities of P3 and an analog, JH-3, bothin vitroandin vivo. The MICs of P3 and JH-3 ranged from 3.125 μg/ml to 50 μg/ml when a wide spectrum of bacteria was tested, including multidrug-resistant strains. P3 killed bacteria within 30 min by disrupting the bacterial cytoplasmic membrane and disturbing the intracellular calcium balance. Circular dichroism (CD) spectrometry showed that P3 assumed an α-helical conformation in bacterial lipid membranes, which was indispensable for antimicrobial activity. Importantly, the 50% lethal dose (LD50) of JH-3 was 180 mg/kg of mouse body weight after intraperitoneal (i.p.) injection, and no death was observed at any dose up to 240 mg/kg body weight following subcutaneous (s.c.) injection. Furthermore, JH-3 significantly decreased the bacterial count and rescued infected mice in a model of mouse bacteremia. In conclusion, P3 and an analog exhibited potent antimicrobial activities and relatively low toxicities in a mouse model, indicating that they may be useful for treating infections caused by drug-resistant bacteria.

scholarly journals Combined Use of the Ab105-2фΔCI Lytic Mutant Phage and Different Antibiotics in Clinical Isolates of Multiresistant Acinetobacter Baumannii

2019 ◽  
Author(s):  
Lucia Blasco ◽  
Anton Ambroa ◽  
Maria Lopez ◽  
Laura Fernandez-Garcia ◽  
Ines Bleriot ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Acinetobacter Baumannii ◽  
Antimicrobial Agents ◽  
Galleria Mellonella ◽  
Resistant Bacteria ◽  
Lytic Phage ◽  
Drug Resistant Bacteria ◽  
Multiresistant Strains

The global health emergency caused by multi-drug resistant bacteria has led to the search for and development of new antimicrobial agents. Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) showing antimicrobial activity against A.baumannii clinical strains (such as Ab177_GEIH-2000 which showed MICs to meropenem and imipenem of 32 µg/ml and 16 µg/ml, respectively as well as belonging to GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585). We then enhanced the time kill curves (in vitro) and in Galleria mellonella survival assays (in vivo) antimicrobial activity of the new lytic phage by combining it with carbapenem antibiotics (meropenem and imipenem). We observed in vitro, an antimicrobial synergistic effect (from 4 log to 7 log CFU/ml) with meropenem plus lytic phage in all combinations analysed (0.1, 1 and 10 MOI of Ab105-2phiΔCI mutant as well as 1/4 and 1/8 MIC of meropenem). Moreover, we had a decrease in bacterial growth of 8 log CFU/ml for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phiΔCI mutant) and of 4 log CFU/ml for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phiΔCI mutant) in both MOI 1 and 10. These results were confirmed in in vivo (G. mellonella) obtaining a higher effectiveness in the combination of imipenem and Ab105-2phiΔCI mutant (P<0.05 by Log Rank-Matel Cox test). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to the antibiotics when used to combat multiresistant strains of Acinetobacter baumannii.

scholarly journals Membrane-active antimicrobial poly(amino-modified alkyl) β-cyclodextrins synthesized via click reactions

MedChemComm ◽  
2018 ◽  
Vol 9 (3) ◽  
pp. 509-518 ◽  
Author(s):  
Hatsuo Yamamura ◽  
Miho Nonaka ◽  
Shingo Okuno ◽  
Ryogo Mitsuhashi ◽  
Hisato Kato ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Hemolytic Activity ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Click Reactions ◽  
Modified Cyclodextrins ◽  
Drug Resistant Bacteria

The modified cyclodextrins exhibited antimicrobial activity against drug-resistant bacteria and less hemolytic activity.

scholarly journals ANTIMICROBIAL ACTIVITIES OF SUCCESSIVE SOLVENT EXTRACTS OF ALBIZIA LEBBECK AND SOLANUM SEAFORTHIANUM AGAINST SOME HUMAN PATHOGENIC MICROORGANISMS

2019 ◽  
pp. 294-296
Author(s):  
HOSUR NARAYANAPPA VENKATESH ◽  
DEVIHALLI CHIKKAIAH MOHANA
Keyword(s):  
Antimicrobial Activity ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Negative Impact ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Albizia Lebbeck ◽  
Minimal Inhibitory Concentrations ◽  
Broth Dilution

Objective: The continuous emergence of multidrug resistance bacteria and yeast, and the negative impact of synthetic preservatives have led to an increased interest in the use of plant extracts as alternative antimicrobial agents. In the present investigation, the antimicrobial activity of successive solvent extracts of Albizia lebbeck and Solanum seaforthianum has been evaluated against human pathogenic bacteria and yeast. Methods: The disc diffusion method was employed for determination of the zone of inhibitions (ZOIs) and twofold broth dilution technique was employed for determination of minimal inhibitory concentrations, and minimal bactericidal/fungicidal concentrations. Results: Among the successive solvent extracts tested, methanol extracts of both A. lebbeck and S. seaforthianum showed highest antibacterial activity with ZOIs ranged between 10.0 and 20.4 mm at 1 mg/disc followed by ethanol (ZOIs 8.1–17.6 mm). The petroleum ether, toluene, and chloroform extracts showed the least activity. The highest activity was observed against Streptococcus faecalis, whereas the least activity was observed against Pseudomonas aeruginosa. Conclusion: The broad-spectrum antimicrobial activity of methanol extract of A. lebbeck and S. seaforthianum could be explored as antimicrobial agents for the management of pathogenic bacteria and yeast.

Synthesis of Some 5-(substituted benzylidene-2, 4-dioxothiazolidin-3-yl) benzoic Acid Derivatives by Conventional and Microwave-assisted Methods and Evaluation of their Potential as Antimicrobial Agents

2019 ◽  
Vol 17 (2) ◽  
pp. 115-129
Author(s):  
Karuna S. Shukla ◽  
Shailendra Pandey ◽  
Pooja Chawla
Keyword(s):  
Antimicrobial Activity ◽  
Benzoic Acid ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Assay Method ◽  
Resistant Bacteria ◽  
Dilution Method ◽  
Chlorobenzoic Acid ◽  
Benzoic Acid Derivatives

<P>Background: Multiple antibiotic resistant bacteria represent a challenge in the treatment of infections. It is imperative, therefore, that new substances with antimicrobial properties should be searched to fight these microorganisms. Objective: A series of 5-benzylidene-2, 4-dioxothiazolidin-3-yl benzoic acid derivatives were synthesized and evaluated their antimicrobial potential. The compounds were synthesized by both conventional and microwave synthesizers. Methods: In this study, a series of 5-benzylidene-2, 4-dioxothiazolidin-3-yl benzoic acid derivatives were synthesized by Knoevenagel condensation of 2, 4-thiazolidinedione with substituted aryl aldehydes followed by substitution of 3-amino group with p-chlorobenzoic acid. All the synthesized compounds were characterized by spectral (FT-IR, mass and 1HNMR) and elemental analysis. The compounds were evaluated for their in-vitro antimicrobial activities against Gram-positive bacteria, Gram-negative bacteria and a fungal strain by agar well diffusion assay method and solid dilution method. Results: The compounds exhibited appreciable antimicrobial activity. Compound 4-(5-(2- chlorobenzylidene)-2, 4-dioxothiazolidin-3-yl)benzoic acid (3f) expressed potent antimicrobial activities against all of the microbial strains examined in this study with MIC values ranging between 0.6-0.8 µg/mL and diameter of the zone of inhibition between 17.2-19.5 mm at the concentration of 200 µg/mL. Conclusion: There was a marked decrease in the reaction time, under mild conditions through microwave synthesis wherein it presented a green approach towards syntheses of the thiazolidinedione derivatives. All compounds exhibited mild to moderate antimicrobial activity. The results of tested bioactive assay showed that the nature of the substituent on the phenyl ring significantly influenced the antimicrobial activity. Among the chloro, bromo and methoxy substituted derivatives, chloro derivative possessed the highest activity followed by bromo and then methoxy. The position of the substituents on the arylidene nucleus also affected the activity and it was found that generally ortho-substituted derivatives showed better antimicrobial activity than others.</P>

scholarly journals Antimicrobial Activity and Mechanism of Functionalized Quantum Dots

Polymers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1670 ◽  
Author(s):  
Keerthiga Rajendiran ◽  
Zizhen Zhao ◽  
De-Sheng Pei ◽  
Ailing Fu
Keyword(s):  
Quantum Dots ◽  
Antimicrobial Activity ◽  
Polyvinylidene Fluoride ◽  
Resistant Bacteria ◽  
Animal Cells ◽  
Antimicrobial Efficiency ◽  
Drug Resistant Bacteria ◽  
Poly Ethylene ◽  
Bacteria And Fungi ◽  
Conventional Antibiotics

An essential characteristic of quantum dots (QDs) is their antimicrobial activity. Compared with conventional antibiotics, QDs not only possess photoluminescence properties for imaging and photodynamic therapy but also have high structural stability. To enhance their antimicrobial efficiency, QDs usually are functionalized by polymers, including poly(ethylene glycol), polyethyleneimine, and poly-l-lysine. Also, QDs conjugated with polymers, such as poly(vinylpyrrolidone) and polyvinylidene fluoride, are prepared as antimicrobial membranes. The main antimicrobial mechanisms of QDs are associated with inducing free radicals, disrupting cell walls/membranes, and arresting gene expression. The different mechanisms from traditional antibiotics allow QDs to play antimicrobial roles in multi-drug-resistant bacteria and fungi. Since the toxicity of the QDs on animal cells is relatively low, they have broad application in antimicrobial research as an effective alternative of traditional antibiotics.

Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

2019 ◽  
Vol 15 (1) ◽  
pp. 63-70
Author(s):  
Shiv Dev Singh ◽  
Arvind Kumar ◽  
Firoz Babar ◽  
Neetu Sachan ◽  
Arun Kumar Sharma
Keyword(s):  
Antimicrobial Activity ◽  
Potassium Hydroxide ◽  
Antimicrobial Agents ◽  
Pyrimidine Ring ◽  
Antimicrobial Activities ◽  
Screening Methods ◽  
Chlorpheniramine Maleate ◽  
In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

scholarly journals Development of Antimicrobial Stapled Peptides Based on Magainin 2 Sequence

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 444
Author(s):  
Motoharu Hirano ◽  
Chihiro Saito ◽  
Hidetomo Yokoo ◽  
Chihiro Goto ◽  
Ryuji Kawano ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Amino Acid ◽  
Hemolytic Activity ◽  
Helical Structure ◽  
Antimicrobial Activities ◽  
Side Chain ◽  
Membrane Disruption ◽  
Amino Acid Residues ◽  
Electrophysiological Measurements ◽  
Cell Membrane Disruption

Magainin 2 (Mag2), which was isolated from the skin of the African clawed frog, is a representative antimicrobial peptide (AMP) that exerts antimicrobial activity via microbial membrane disruption. It has been reported that the helicity and amphipathicity of Mag2 play important roles in its antimicrobial activity. We investigated and recently reported that 17 amino acid residues of Mag2 are required for its antimicrobial activity, and accordingly developed antimicrobial foldamers containing α,α-disubstituted amino acid residues. In this study, we further designed and synthesized a set of Mag2 derivatives bearing the hydrocarbon stapling side chain for helix stabilization. The preferred secondary structures, antimicrobial activities, and cell-membrane disruption activities of the synthesized peptides were evaluated. Our analyses revealed that hydrocarbon stapling strongly stabilized the helical structure of the peptides and enhanced their antimicrobial activity. Moreover, peptide 2 stapling between the first and fifth position from the N-terminus showed higher antimicrobial activity than that of Mag2 against both gram-positive and gram-negative bacteria without exerting significant hemolytic activity. To investigate the modes of action of tested peptides 2 and 8 in antimicrobial and hemolytic activity, electrophysiological measurements were performed.

scholarly journals Biological and Physico-Chemical Characteristics of Arginine-Rich Peptide Gemini Surfactants with Lysine and Cystine Spacers

2021 ◽  
Vol 22 (7) ◽  
pp. 3299
Author(s):  
Damian Neubauer ◽  
Maciej Jaśkiewicz ◽  
Marta Bauer ◽  
Agata Olejniczak-Kęder ◽  
Emilia Sikorska ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Amino Acid ◽  
Cationic Surfactants ◽  
Antimicrobial Agents ◽  
Gemini Surfactants ◽  
Antimicrobial Activities ◽  
Critical Aggregation Concentration ◽  
Cytotoxic Activities ◽  
Candida Sp ◽  
Enhanced Selectivity

Ultrashort cationic lipopeptides (USCLs) and gemini cationic surfactants are classes of potent antimicrobials. Our recent study has shown that the branching and shortening of the fatty acids chains with the simultaneous addition of a hydrophobic N-terminal amino acid in USCLs result in compounds with enhanced selectivity. Here, this approach was introduced into arginine-rich gemini cationic surfactants. L-cystine diamide and L-lysine amide linkers were used as spacers. Antimicrobial activity against planktonic and biofilm cultures of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) strains and Candida sp. as well as hemolytic and cytotoxic activities were examined. Moreover, antimicrobial activity in the presence of human serum and the ability to form micelles were evaluated. Membrane permeabilization study, serum stability assay, and molecular dynamics were performed. Generally, critical aggregation concentration was linearly correlated with hydrophobicity. Gemini surfactants were more active than the parent USCLs, and they turned out to be selective antimicrobial agents with relatively low hemolytic and cytotoxic activities. Geminis with the L-cystine diamide spacer seem to be less cytotoxic than their L-lysine amide counterparts, but they exhibited lower antibiofilm and antimicrobial activities in serum. In some cases, geminis with branched fatty acid chains and N-terminal hydrophobic amino acid resides exhibited enhanced selectivity to pathogens over human cells.

scholarly journals Novel Acetohydrazide Pyrazole Derivatives: Design, Synthesis, Characterization and Antimicrobial Activity

2019 ◽  
Vol 31 (12) ◽  
pp. 2740-2744
Author(s):  
Anil Verma ◽  
Vinod Kumar ◽  
Ramesh Kataria ◽  
Joginder Singh
Keyword(s):  
Mass Spectrometry ◽  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Pyrazole Derivatives ◽  
Reaction Conditions ◽  
Design Synthesis ◽  
Structure Activity ◽  
Electron Withdrawing Group ◽  
Sar Study

Eleven acetohydrazide linked pyrazole derivatives were designed and synthesized via condensation of acetohyadrazide with different substituted formyl pyrazole derivatives under mild reaction conditions. Synthesized compounds were characterized on the basis of IR, NMR (1H & 13C) and mass spectrometry. The antimicrobial activities of all the compounds were screened against four bacterial and two fungal strains. Among the synthesized compounds, three compounds viz. 6b, 6c and 6d were found as efficient antimicrobial agents in reference to the standard drugs viz. ciprofloxacin and amphotericin-B. Further, structure-activity relationship (SAR) study revealed that electron-withdrawing group enhances the antimicrobial potential of synthesized derivatives as compared to other groups present in the ring. Hence, among compounds 6b-c, compound 6d could be explored further against other microbes to prove its vitality.

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