Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD)

American oyster defensin (AOD) was previously purified from acidified gill extract of the American oyster, Crassostrea virginica. AOD is composed of 38 amino acids with three disulfide bonds and exhibits strong antimicrobial activity against Gram-positive bacteria as well as significant activity against Gram-negative bacteria. Here, to develop promising peptides into antibiotic candidates, we designed five arginine-rich analogs (A0, A1, A2, A3, and A4), predicted their loop and extended strand/random structures—including nine amino acids and a disulfide bond derived from the C-terminus of AOD—and described their antimicrobial and cytotoxic effects, as well as their modes of action. In our experimental results, the A3 and A4 analogs exhibited potent antimicrobial activity against all test organisms—including four Gram-positive bacteria, six Gram-negative bacteria, and Candida albicans—without cell toxicity. A sequence of experiments, including a membrane permeabilization assay, DNA binding study, and DNA polymerization inhibition test, indicated that the two analogs (A3 and A4) possibly did not act directly on the bacterial membrane but instead interacted with intracellular components such as DNA or DNA amplification reactions. AOD analogs also showed strong bacterial inhibition activity in the plasma environment. In addition, analog-treated microbial cells clearly exhibited membrane disruption, damage, and leakage of cytoplasmic contents. Collectively, our results suggest that two analogs, A3 and A4, have potent antimicrobial activity via DNA interaction and have the potential for development into novel antimicrobial agents.

Download Full-text

Enaminone-Derived Pyrazoles with Antimicrobial Activity

Journal of Chemistry ◽

10.1155/2019/2467970 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10

Author(s):

Mashooq Ahmad Bhat ◽

Mohamed A. Al-Omar ◽

Ahmed M. Naglah ◽

Abdul Arif Khan

Keyword(s):

Antimicrobial Activity ◽

Gram Negative Bacteria ◽

Significant Activity ◽

Disc Diffusion ◽

Initial Screening ◽

Gram Positive ◽

Gram Negative ◽

Disc Diffusion Assay ◽

Gram Positive Bacteria ◽

Diffusion Assay

A series of pyrazoles derived from the substituted enaminones were synthesized and were evaluated for antimicrobial activity. All the compounds were characterized by the spectral data and elemental analysis. The synthesized compounds were initially screened for their antimicrobial activity against ATCC 6538, NCTC 10400, NCTC 10418, and ATCC 27853. During initial screening, compounds (P1, P6, and P11) presented significant antimicrobial activity through disc diffusion assay. These compounds were further evaluated for antimicrobial activity at different time points against Gram-positive and Gram-negative bacteria and presented significant activity for 6 hours. The activity was found to be greater against Gram-positive bacteria. In contrast at 24 hours, the activity was found only against Gram-positive bacteria except compound (P11), showing activity against both types of bacteria. Compound (P11) was found to have highest activity against both Gram-positive and Gram-negative bacteria.

Download Full-text

Replacement of l-Amino Acids by d-Amino Acids in the Antimicrobial Peptide Ranalexin and Its Consequences for Antimicrobial Activity and Biodistribution

Molecules ◽

10.3390/molecules24162987 ◽

2019 ◽

Vol 24 (16) ◽

pp. 2987 ◽

Cited By ~ 2

Author(s):

Cornelius Domhan ◽

Philipp Uhl ◽

Christian Kleist ◽

Stefan Zimmermann ◽

Florian Umstätter ◽

...

Keyword(s):

Amino Acids ◽

Antimicrobial Activity ◽

Antimicrobial Peptide ◽

The Body ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Strong Antimicrobial Activity

Infections caused by multidrug-resistant bacteria are a global emerging problem. New antibiotics that rely on innovative modes of action are urgently needed. Ranalexin is a potent antimicrobial peptide (AMP) produced in the skin of the American bullfrog Rana catesbeiana. Despite strong antimicrobial activity against Gram-positive bacteria, ranalexin shows disadvantages such as poor pharmacokinetics. To tackle these problems, a ranalexin derivative consisting exclusively of d-amino acids (named danalexin) was synthesized and compared to the original ranalexin for its antimicrobial potential and its biodistribution properties in a rat model. Danalexin showed improved biodistribution with an extended retention in the organisms of Wistar rats when compared to ranalexin. While ranalexin is rapidly cleared from the body, danalexin is retained primarily in the kidneys. Remarkably, both peptides showed strong antimicrobial activity against Gram-positive bacteria and Gram-negative bacteria of the genus Acinetobacter with minimum inhibitory concentrations (MICs) between 4 and 16 mg/L (1.9–7.6 µM). Moreover, both peptides showed lower antimicrobial activities with MICs ≥32 mg/L (≥15.2 µM) against further Gram-negative bacteria. The preservation of antimicrobial activity proves that the configuration of the amino acids does not affect the anticipated mechanism of action, namely pore formation.

Download Full-text

Synthesis and Evaluation of Some Coumarin Based Schiff's Bases as Potential Antimicrobial Agents'

E-Journal of Chemistry ◽

10.1155/2012/791091 ◽

2012 ◽

Vol 9 (4) ◽

pp. 2079-2088 ◽

Cited By ~ 1

Author(s):

Vishakha Bansode ◽

Meenakshi N. Deodhar

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Agents ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

H Nmr ◽

Nmr Data ◽

Bacteria And Fungi

A series of the title compounds 3-(4-(4, 5-dihydro-5-(substituted phenyl)-1H-3-pyrazolyl) phenylimino) methyl)-4-chloro-2H-chromen-2-one 5(a-g) have been synthesized. These compounds were characterized on the basis of their spectral (IR,1H NMR) data and evaluated for antimicrobial activityin vitroagainst gram positive bacteria, gram negative bacteria and fungi. The compound (5b) was found to be the most active with MIC of 20 µg/ml against all the tested organisms.

Download Full-text

Synthesis, Spectroscopy, Single-Crystal Structure Analysis and Antibacterial Activity of Two Novel Complexes of Silver(I) with Miconazole Drug

International Journal of Molecular Sciences ◽

10.3390/ijms22041510 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1510 ◽

Cited By ~ 1

Author(s):

Karolina Stryjska ◽

Izabela Korona-Glowniak ◽

Lilianna Chęcińska ◽

Joachim Kusz ◽

Justyn Ochocki

Keyword(s):

Antimicrobial Activity ◽

Free Ligand ◽

Silver Sulfadiazine ◽

Moderate Activity ◽

Gram Negative Bacteria ◽

Significant Activity ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Silver Salts

In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)2NO3 (1)] and [Ag(MCZ)2ClO4 (2)] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = BF4− (3), SbF6− (4)). The novel silver(I) complexes were characterized by elemental analysis, 1H NMR, 13C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.

Download Full-text

Antimicrobial activity of Pycnarrhena cauliflora (Miers.) Diels. methanol extract

Indonesian Journal of Pharmacology and Therapy ◽

10.22146/ijpther.1656 ◽

2021 ◽

Vol 2 (2) ◽

Author(s):

Eti Nurwening Sholikhah ◽

Maulina Diah ◽

Mustofa ◽

Masriani ◽

Susi Iravati ◽

...

Keyword(s):

Antimicrobial Activity ◽

Methanolic Extract ◽

Biological Activities ◽

Positive Control ◽

Diffusion Method ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Methanolic Extracts

Pycnarrhena cauliflora (Miers.) Diels., local name sengkubak, is one of indigenous plants from West Kalimantan that has been used as natural flavor. Pycnorrhena cauliflora is one of species of Menispermaceae family which is rich in bisbenzylisoquinoline alkaloids. This alkaloids are known to have various biological activities including antiprotozoal, antiplasmodial, antifungal and antibacterial activities. This study aimed to investigate antimicrobial activity of the P. cauliflora (Miers.) Diels. methanolic extracts against gram-positive and gram-negative bacteria. The methanolic extract of P. cauliflora (Miers.) Diels., root, leaf and stem were prepared by maceration. The disk-diffusion method was then used to determine the antimicrobial activity of the extracts against Streptococcus pyogenes, S. mutants, Staphylococcus aureus, S. epidermidis, Salmonella typhi, Shigella flexneri, Pseudomonas aeruginosa and Escherichia coli after 18-24 h incubation at 37 oC. Amoxicillin was used as positive control for gram-positive bacteria and ciprofloxacin was used as gram-negative bacteria. The inhibition zones were then measured in mm. Analysis were conducted in duplicates. The results showed in general the methanolic extracts of P. cauliflora (Miers.) Diels. root (inhibition zone diameter= 10-23 mm) were more active than that leaf (0-15 mm) and stem (0-17 mm) extracts against gram-positive bacteria. The zone inhibition diameter of amoxicillin as positive control was 8-42 mm. In addition, the methanolic extracts of P. cauliflora (Miers.) Diels. root (12-17 mm) were also more active than that leaf (0-12 mm) and stem (0-12 mm) extracts against gram-negative bacteria. The zone inhibition diameter of ciprofloxacin as positive control was 33-36 mm. In conclusion, the methanolic extract of P. caulifloria (Miers.) Diels. root is the most extract active against both gram-positive and gram-negative bacteria. Further study will be focused to isolate active compounds in the methanolic extract of the root.

Download Full-text

ANTIMICROBIAL ACTIVITY OF COPPER KAOLINITE AND SURFACTANT MODIFIED COPPER KAOLINITE AGAINST GRAM POSITIVE AND GRAM NEGATIVE BACTERIA

Jurnal Teknologi ◽

10.11113/jt.v78.7827 ◽

2016 ◽

Vol 78 (3-2) ◽

Author(s):

Nor Syafawani Sarah Md Saad ◽

Nik Ahmad Nizam Nik Malek ◽

Chun Shiong Chong

Keyword(s):

Antimicrobial Activity ◽

Synergistic Effects ◽

Wide Spectrum ◽

Copper Nitrate ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

X Ray ◽

Gram Positive Bacteria ◽

Diffusion Technique

The aim of this research was to determine the antimicrobial activity of kaolinite modified with antimicrobial compounds against Gram positive and Gram negative bacteria. Copper kaolinite (Cu-kaolinite) was prepared by loading raw kaolinite with copper nitrate trihydrate (CuNO3) while surfactant modified Cu-kaolinite (SM-Cu-kaolinite) was prepared by adding cationic surfactants hexadecyltrimethyl ammonium (HDTMA) on Cu-Kaolinite. Samples was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analyzer. The antimicrobial activity of the samples was tested against Gram negative bacteria (Escherichia coli ATCC 11229 and Pseudomonas aeruginosa ATCC 15442), and Gram positive bacteria (Staphylococcus aureus ATCC 6538 and Enterococcus faecalis ATCC 29212) through disc diffusion technique (DDT) and minimum inhibition concentration (MIC). The results showed that the antimicrobial activity of Cu-kaolinite increased after modified with HDTMA due to the synergistic effects of Cu ions and HDTMA molecules on the kaolinite. The antimicrobial activity for surfactant modified Cu-kaolinite was greater for Gram positive bacteria compared to Gram negative bacteria. In conclusion, the attachment of HDTMA on Cu-kaolinite contributed to the enhanced antimicrobial activity against wide spectrum of bacteria (Gram positive and Gram negative bacteria).

Download Full-text

DESIGN, SYNTHESIS, DOCKING STUDIES AND BIOLOGICAL EVALUATION OF 2-PHENYL-3-(SUBSTITUTED BENZO[d] THIAZOL-2-YLAMINO)-QUINAZOLINE-4(3H)-ONE DERIVATIVES AS ANTIMICROBIAL AGENTS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i10.28480 ◽

2018 ◽

Vol 10 (10) ◽

pp. 57

Author(s):

Pooja Pisal ◽

Meenakshi Deodhar ◽

Amol Kale ◽

Ganesh Nigade ◽

Smita Pawar

Keyword(s):

Antimicrobial Agents ◽

Docking Studies ◽

Biological Evaluation ◽

Spectral Studies ◽

Gram Negative Bacteria ◽

Significant Activity ◽

Fusion Reactions ◽

Gram Positive ◽

Gram Negative

Objective: A new series 2-phenyl-3-(substituted benzo[d] thiazol-2-ylamino)-quinazoline-4(3H)-one was prepared by the fusion method by reacting 2-phenyl benzoxazine with 2-hydrazino benzothiazole and it was evaluated for their antimicrobial activity against gram positive, gram negative bacteria and fungi.Methods: Titled compounds were synthesized by fusion reactions. These compounds were evaluated by in vitro antibacterial and antifungal activity using the minimum inhibitory concentration and zone of inhibition methods. The synthesized compounds were characterized with the help of infrared, NMR and mass spectral studies. The benzothiazole moiety and the quinazoline ring have previously shown DNA gyrase inhibition and target related antibacterial activity. Thus, molecular docking studies of synthesized compounds were carried out (PDB: 3G75) to study the possible interaction of compounds with the target. The batch grid docking was performed to determine the probable.Results: These compounds showed significant activity against gram positive and gram negative bacteria as well against the fungi. The compound A5 was found to be active against B. subtilis, P aeruginosa and C. albican at 12.5 µg/ml MIC. The compound A3 was found to be active against all microbial strains selected at 25 and 12.5 µg/ml MIC.Conclusion: Though the relationship between the activities shown by these compounds in, the antimicrobial study is still to be established, the docking studies conducted found to be consistent with antimicrobial results. Thus the results indicate that the designed structure can be a potential lead as an antimicrobial agent.

Download Full-text

Increases in Hydrophilicity and Charge on the Polar Face of Alyteserin 1c Helix Change its Selectivity towards Gram-Positive Bacteria

Antibiotics ◽

10.3390/antibiotics8040238 ◽

2019 ◽

Vol 8 (4) ◽

pp. 238 ◽

Cited By ~ 5

Author(s):

Yamil Liscano ◽

Constain H. Salamanca ◽

Lina Vargas ◽

Stefania Cantor ◽

Valentina Laverde-Rojas ◽

...

Keyword(s):

Antimicrobial Activity ◽

Solid Phase ◽

Structural Characteristics ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Mutant Derivative ◽

Conventional Antibiotics ◽

Carboxy Terminal

Recently, resistance of pathogens towards conventional antibiotics has increased, representing a threat to public health globally. As part of the fight against this, studies on alternative antibiotics such as antimicrobial peptides have been performed, and it has been shown that their sequence and structure are closely related to their antimicrobial activity. Against this background, we here evaluated the antibacterial activity of two peptides developed by solid-phase synthesis, Alyteserin 1c (WT) and its mutant derivative (ΔM), which shows increased net charge and reduced hydrophobicity. These structural characteristics were modified as a result of amino acid substitutions on the polar face of the WT helix. The minimum inhibitory concentration (MIC) of both peptides was obtained in Gram-positive and Gram-negative bacteria. The results showed that the rational substitutions of the amino acids increased the activity in Gram-positive bacteria, especially against Staphylococcus aureus, for which the MIC was one-third of that for the WT analog. In contrast to the case for Gram-positive bacteria, these substitutions decreased activity against Gram-negative bacteria, especially in Escherichia coli, for which the MIC was eight-fold higher than that exhibited by the WT peptide. To understand this, models of the peptide behavior upon interacting with membranes of E. coli and S. aureus created using molecular dynamics were studied and it was determined that the helical stability of the peptide is indispensable for antimicrobial activity. The hydrogen bonds between the His20 of the peptides and the phospholipids of the membranes should modulate the selectivity associated with structural stability at the carboxy-terminal region of the peptides.

Download Full-text

Аntibacterial inorganic agents: efficiency of using multicomponent systems

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-aia-1512 ◽

2020 ◽

Vol 10 (4) ◽

pp. 639-654

Author(s):

А. A. Meleshko ◽

A. G. Afinogenova ◽

G. E. Afinogenov ◽

A. A. Spiridonova ◽

V. P. Tolstoy

Keyword(s):

Antimicrobial Activity ◽

Antibacterial Activity ◽

Antimicrobial Agents ◽

Metal Oxide Nanoparticles ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Nanoscale Systems ◽

Gram Negative ◽

Low Toxicity

Metal and metal oxide nanoparticles (NPs) are promising antibacterial agents. They have a broad antimicrobial activity against both Gram-positive and Gram-negative bacteria, viruses, and protozoans. The use of NPs reduces the possibility of the microbial resistance development. This review briefly shows the general mechanisms and the main factors of antibacterial activity of NPs. In this article, a comprehensive review of the recent researches in the field of new antimicrobial agents with superior long-term bactericidal activity and low toxicity is provided. The review gives the examples of synthesis of double and triple nanocomposites based on following oxides: CuO, ZnO, Fe3O4, Ag2O, MnO2, etc. including metal and nonmetal doped nanocomposites (for example with Ag, Ce, Cr, Mn, Nd, Co, Sn, Fe, N, F, etc.). Compared with bactericidal action of individual oxides, the nanocomposites demonstrate superior antibacterial activity and have synergistic effects. For example, the antimicrobial activity of ZnO against both Gram-positive and Gram-negative bacteria was increased by -100% by formation of triple nanocomposites ZnO—MnO2—Cu2O or ZnO—Ag2O—Ag2S. Similar effect was showed for Ce-doped ZnO and Zn-doped CuO. The present article also provides the examples of nanocomposites containing NPs and organic (chitosan, cellulose, polyvinylpyrrolidone, biopolymers, etc.) or inorganic materials with special structure (graphene oxide, TiO2 nanotubes, silica) which demonstrate controlled release and longterm antibacterial activity. All of the considered nanocomposites and their combinations have a pronounced long-term antimicrobial effect including against antibiotic-resistant strains. They are able to prevent the formation of microbial biofilms on biotic and abiotic surfaces, have low toxicity to eukaryotic cells, demonstrate anti-inflammatory and woundhealing properties in compositions with polymers (sodium alginate, collagen, polyvinylpyrrolidone, etc.). The use of nanoscale systems can solve several important practical problems at the same time: saving of long-term antimicrobial activities while reducing the number of compounds, creation of new antimicrobial agents with low toxicity and reduced environmental impact, development of new biocidal materials, including new coatings for effective antimicrobial protection of medical devices.

Download Full-text

Composition and Antimicrobial Activity of the Essential Oil of a Wild Kiwi

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.322.160 ◽

2011 ◽

Vol 322 ◽

pp. 160-163

Author(s):

Yin Lu ◽

Hong Chen

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Antimicrobial Activity ◽

Fungal Species ◽

Gram Negative Bacteria ◽

Significant Activity ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Leaf Oil ◽

First Time

A medicinal wild kiwi in China, Actinidia valvata Dunn, has been well known for its activities against leprosy and cancers. The compositions and the antimicrobial activity of its leaf oil were reported for the first time. The oil obtained by hydrodistillation and analyzed by GC and GC-MS, was characterized by the high content of monoterpenes. Linalool (48.14%) is the major component identified, followed by 1,2-dimethyl-lindoline (7.94%), linolenic acid methylester (6.57%) and (E)-phytol (5.29%). The antimicrobial activity of the oil was evaluated against four bacterial and three fungal species. The results showed that it exhibited a mild antibacterial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), a significant activity against Gram-negative bacteria (Escherichia coli), and no activity on Pseudomonas aeruginosa. The test fungi were more sensitive to the oil, with a MIC range of 0.78~1.56 μL/mL than bacteria in the range which were significantly higher from 0.78 to 25.50 μL/mL.

Download Full-text