Ellagic acid: A potent glyoxalase-I inhibitor with a unique scaffold

The glyoxalase system, particularly glyoxalase-I (GLO-I), has been approved as a potential target for cancer treatment. In this study, a set of structurally diverse polyphenolic natural compounds were investigated as potential GLO-I inhibitors. Ellagic acid was found, computationally and experimentally, to be the most potent GLO-I inhibitor among the tested compounds which showed an IC50 of 0.71 mol L–1. Its binding to the GLO-I active site seemed to be mainly driven by ionic interaction via its ionized hydroxyl groups with the central Zn ion and Lys156, along with other numerous hydrogen bonding and hydrophobic interactions. Due to its unique and rigid skeleton, it can be utilized to search for other novel and potent GLO-I inhibitors via computational approaches such as pharmacophore modeling and similarity search methods. Moreover, an inspection of the docked poses of the tested compounds showed that chlorogenic acid and dihydrocaffeic acid could be considered as lead compounds worthy of further optimization

Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens

This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility

The evaluation of the synergistic antimicrobial and antibiofilm activity of AamAP1-Lysine with conventional antibiotics against representative resistant strains of both Gram-positive and Gram-negative bacteria

Ammar Almaaytah,1 Ahmad Abualhaijaa,2 Obadah Alqudah31Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Applied Biological Sciences, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Legal Medicine, Toxicology and Forensic Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, JordanBackground and purpose: Antimicrobial resistance toward antibiotics is reaching historical unprecedented levels. There is an urgent and imminent need to develop novel antimicrobial alternatives. Antimicrobial peptides could prove to be a successful group of antimicrobials for drug development. Recently, we have designed a novel synthetic peptide named AamAP1-Lysine. The peptide displayed potent wide-spectrum antimicrobial activities against Gram-positive and Gram-negative bacteria. The purpose of this study is to evaluate the antimicrobial effect of combining AamAP1-Lysine with five different conventional antibiotics each representing a distinct mechanism of action in order to explore the possibility of producing a synergistic mode of action against a resistant strain of Gram-positive and a resistant strain of Gram-negative bacteria.Methodology: The antimicrobial activity of AamAP1-Lysine in combination with five different antibiotics were evaluated for their antimicrobial activity employing standard antimicrobial assays, the synergistic activity of the peptide-antibiotic combinations were evaluated using checkerboard technique in addition to real-time time-kill assays. For the antibiofilm studies, the MBEC values were determined by employing the Calgary device.Results: The combination strategy displayed potent synergistic activities against planktonic bacteria in a significant number of peptide-antibiotic combinations. The synergistic activity managed to reduce the effective minimum inhibitory concentration (MIC) concentrations dramatically with some combinations exhibiting a 64-fold decrease in the effective MIC of AamAP1-Lysine individually. Additionally, the combined synergistic activities of the peptide antibiotics were evaluated, and our results have identified two peptide antibiotic combinations with potent synergistic activities against biofilm growing strains of resistant bacteria.Conclusion: Our results clearly indicate that peptide-antibiotic combinations could prove to be a very effective strategy in combatting multidrug-resistant bacteria and biofilm caused infections.Keywords: antimicrobial peptides, AamAP1-Lysine, bacterial resistance, antibiofilm, synerg

In vivo antimicrobial activity of the hybrid peptide H4: a follow-up study

Ammar Almaaytah,1 Qosay Albalas,2 Karem H Alzoubi3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Medicinal Chemistry and Pharmacognosy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Background: The consistent upsurge in antimicrobial resistance globally is threatening the world population with the prospect of facing the post-antibiotic era. Dry pipelines and a drastic decrease of antimicrobial drug development accompany this rise in antimicrobial resistance. Governments and health authorities are calling for the development of novel classes of antimicrobial agents that would tackle this problem. Antimicrobial peptides represent a promising group of molecules for antimicrobial drug development due to their potency and rapid mode of killing. However, several obstacles, such as high mammalian cell toxicity and lack of target selectivity, have challenged the development of such agents. Methods: We have recently designed a novel hybrid peptide named H4 that exhibits potent antimicrobial activity and low toxicity in vitro. In order to confirm the potential therapeutic efficacy and safety of the peptide, we evaluated the in vivo activity and toxicity of H4 against Staphylococcus aureus peritonitis mice model. Results: Our results indicate that H4 is highly potent in eradicating bacterial infections in vivo with an effective dose50 value of 4.55±0.89 mg/kg. Additionally, the acute systemic toxicity results indicate that the peptide exhibits a high therapeutic index with no significant negative effects on the function of major body organs. Conclusion: H4 is a novel hybrid peptide with great potential for antimicrobial drug development. Keywords: antimicrobial peptides, hybrid peptides, in vivo activity, hybridization, antimicrobial resistance, drug developmen

Dispensing of non-prescribed antibiotics in Jordan

Ammar Almaaytah,1 Tareq L Mukattash,2 Julia Hajaj2 1Department of Pharmaceutical Technology, 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Objective: Current regulations in Jordan state that antibiotics cannot be sold without a medical prescription. This study aimed to assess the percentage of pharmacies that dispense antibiotics without a medical prescription in the Kingdom of Jordan and identify and highlight the extent and seriousness of such practices among Jordanian pharmacies. Methods: A prospective study was performed, and five different clinical scenarios were simulated at pharmacies investigated including sore throat, otitis media, acute sinusitis, diarrhea, and urinary tract infection in childbearing-aged women. Three levels of demand were used to convince the pharmacists to sell an antibiotic. Results: A total of 202 total pharmacies in Jordan were visited in the present study. The majority of pharmacies (74.3%) dispensed antibiotics without prescription with three different levels of demand. The percentage of pharmacies dispensing antibiotics without a prescription for the sore throat scenario was 97.6%, followed by urinary tract infection (83.3%), diarrhea (83%), and otitis media (68.4%). The lowest percentage of antibiotic dispensing was for the acute sinusitis simulation at 48.5%. Among the pharmacies that dispensed antibiotics, the pharmacists provided an explanation as the number of times per day the drug should be taken in 95.3% of the cases, explained the duration of treatment in 25.7%, and inquired about allergies prior to the sale of the antibiotic in only 17.3%. Only 52 pharmacies (25.7%) refused to dispense any kind of antibiotics, the majority (61.5%) of this refusal response came from acute sinusitis cases, while the minority (2.4%) came from the sore throat cases. Conclusion: The results of this study demonstrate that antibiotics continue to be dispensed without prescription in Jordan in violation with national regulations regarding this practice. The findings of this study could provide a layout for governmental health authorities to implement strict enfrorcment of national regulations regarding antibiotic dispensing in order to avoid the serious complications that could arise in the future as a result of such practices. Keywords: pharmacy, pharmacy practice, non-prescribed antibiotics, microbial resistance, Jorda

English Proverbs into Arabic through Machine Translation

Proverbs are sentences used by people to convey wisdom, truth or morals that have been handed down for generations. Translating them from one language into another through machine translation has been a matter of interest because of their importance in keeping the religious, cultural and historical aspects. The accuracy of machine translation systems has become one of the most important issues nowadays as the demand for online translation is increasing. Therefore, the current study aimed at investigating the linguistic obstacles that machine translation might face in carrying out the same translation from English proverbs into Arabic. It also attempted to confirm the importance of human intervention in solving the issue of accuracy. To achieve these objectives, a group of English proverbs were randomly selected, translated into Arabic by ‘Google translate’ and analysed qualitatively by the researchers. On the one hand, the findings revealed that ‘Google translate’ faced some linguistic obstacles in carrying out the same meaning of English proverbs into Arabic. Lexically, words that have multiple meanings present countless challenges and difficulties to online translation. On the other hand, the different linguistic structures between English and Arabic make the process of translation sometimes a bit challenging as both languages belong to unrelated families. Simply put, machine translation is expected to encounter various problems in providing meaningful logical translation. A detailed discussion is provided and recommendations for further research are given based on the analysis

Development of novel ultrashort antimicrobial peptide nanoparticles with potent antimicrobial and antibiofilm activities against multidrug-resistant bacteria

Ammar Almaaytah,1 Gubran Khalil Mohammed,1 Ahmad Abualhaijaa,2 Qosay Al-Balas3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, 2Department of Applied Biological Sciences, Faculty of Science and Arts, 3Department of Medicinal Chemistry, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Abstract: Conventional antibiotics are facing strong microbial resistance that has recently reached critical levels. This situation is leading to significantly reduced therapeutic potential of a huge proportion of antimicrobial agents currently used in clinical settings. Antimicrobial peptides (AMPs) could provide the medical community with an alternative strategy to traditional antibiotics for combating microbial resistance. However, the development of AMPs into clinically useful antibiotics is hampered by their relatively low stability, toxicity, and high manufacturing costs. In this study, a novel in-house-designed potent ultrashort AMP named RBRBR was encapsulated into chitosan-based nanoparticles (CS-NPs) based on the ionotropic gelation method. The encapsulation efficacy reported for RBRBR into CS-NPs was 51.33%, with a loading capacity of 10.17%. The release kinetics of RBRBR from the nanocarrier exhibited slow release followed by progressive linear release for 14 days. The antibacterial kinetics of RBRBR-CS-NPs was tested against four strains of Staphylococcus aureus for 4 days, and the developed RBRBR-CS-NPs exhibited a 3-log decrease in the number of colonies when compared to CS-NP and a 5-log decrease when compared to control bacteria. The encapsulated peptide NP formulation managed to limit the toxicity of the free peptide against both mammalian cells and human erythrocytes. Additionally, the peptide NPs demonstrated up to 98% inhibition of biofilm formation when tested against biofilm-forming bacteria. Loading RBRBR into CS-NPs could represent an innovative approach to develop delivery systems based on NP technology for achieving potent antimicrobial effects against multidrug-resistant and biofilm-forming bacteria, with negligible systemic toxicity and reduced synthetic costs, thereby overcoming the obstructions to clinical development of AMPs. Keywords: ultrashort antimicrobial peptides, nanoparticles, drug delivery, antibiofil

Hybridization and antibiotic synergism as a tool for reducing the cytotoxicity of antimicrobial peptides

Ammar Almaaytah,1 Mohammed T Qaoud,1 Ahmad Abualhaijaa,2 Qosay Al-Balas,3 Karem H Alzoubi4 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Applied Biological Sciences, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Medicinal Chemistry, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 4Department Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Introduction: As the development of new antimicrobial agents faces a historical decline, the issue of bacterial drug resistance has become a serious dilemma that threatens the human population worldwide. Antimicrobial peptides (AMPs) represent an attractive and a promising class of antimicrobial agents. Aim: The hybridization of AMPs aimed at merging two individual active fragments of native peptides to generate a new AMP with altered physicochemical properties that translate into an enhanced safety profile. Materials and methods: In this study, we have rationally designed a new hybrid peptide via combining two individual α-helical fragments of both BMAP-27 and OP-145. The resultant peptide, was evaluated for its antimicrobial and antibiofilm activity against a range of microbial strains. The resultant peptide was also evaluated for its toxicity against mammalian cells using hemolytic and anti proliferative assays. Results: The antimicrobial activity of H4 revealed that the peptide is displaying a broad spectrum of activity against both Gram-positive and Gram-negative bacteria including standard and multidrug-resistant bacterial strains in the range of 2.5–25 μM. The new hybrid peptide displayed potent activity in eradicating biofilm-forming cells, and the reported minimum biofilm eradication concentrations were equal to the minimum inhibitory concentration values reported for planktonic cells. Additionally, H4 exhibited reduced toxicity profiles against eukaryotic cells. Combining H4 peptide with conventional antibiotics has led to a dramatic enhancement of the antimicrobial activity of both agents with synergistic or additive outcomes. Conclusion: Overall, this study indicates the success of both the hybridization and synergism strategy in developing AMPs as potential antimicrobial therapeutics with reduced toxicity profiles that could be efficiently employed to eradicate resistant bacterial strains and enhance the selectivity and toxicity profiles of native AMPs. Keywords: antimicrobial peptides, peptide hybridization, antibiotic synergism, biofilms, antimicrobial resistanc

Peptide consensus sequence determination for the enhancement of the antimicrobial activity and selectivity of antimicrobial peptides

Ammar Almaaytah,1 Ya’u Ajingi,2 Ahmad Abualhaijaa,2 Shadi Tarazi,2 Nizar Alshar’i,3 Qosay Al-Balas3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Applied Biological Sciences, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Medicinal Chemistry, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan Abstract: The rise of multidrug-resistant bacteria is causing a serious threat to the world’s human population. Recent reports have identified bacterial strains displaying pan drug resistance against antibiotics and generating fears among medical health specialists that humanity is on the dawn of entering a post-antibiotics era. Global research is currently focused on expanding the lifetime of current antibiotics and the development of new antimicrobial agents to tackle the problem of antimicrobial resistance. In the present study, we designed a novel consensus peptide named “Pepcon” through peptide consensus sequence determination among members of a highly homologous group of scorpion antimicrobial peptides. Members of this group were found to possess moderate antimicrobial activity with significant toxicity against mammalian cells. The aim of our design method was to generate a novel peptide with an enhanced antimicrobial potency and selectivity against microbial rather than mammalian cells. The results of our study revealed that the consensus peptide displayed potent antibacterial activities against a broad range of Gram-positive and Gram-negative bacteria. Our membrane permeation studies displayed that the peptide efficiently induced membrane damage and consequently led to cell death through the process of cell lysis. The microbial DNA binding assay of the peptide was found to be very weak suggesting that the peptide is not targeting the microbial DNA. Pepcon induced minimal cytotoxicity at the antimicrobial concentrations as the hemolytic activity was found to be zero at the minimal inhibitory concentrations (MICs). The results of our study demonstrate that the consensus peptide design strategy is efficient in generating peptides. Keywords: peptide, scorpion, venom, peptide design, antimicrobial peptides, consensus sequenc