Biological activities and phenolic contents of Argania spinosa L (Sapotaceae) leaf extract

Purpose: To investigate the phenolic profile and biological activities of Argania spinosa L. leaves.Methods: The crude methanol extract of leaves of A. spinosa L. Skeels was obtained by ultrasonic extraction, and the total polyphenolic and flavonoid contents were determined by ultra-high performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry (UPLC-ESIQTOF- MS). In vitro antioxidant activity was determined by 2,2-di-phenyl-1-picryl-hydrazil (DPPH) radical assay and antimicrobial activity evaluated using agar disk diffusion method against reference pathogenic strains (Bacillus subtilis ATCC 6633, Bacillus cereus ATCC 14579, Yersinia enterocolitica ATCC 23715, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922). Cytotoxic activity was evaluated by methyl-thiazolyldiphenyl-tetrazolium bromide (MTT) assay.Results: The results revealed abundant polyphenols and flavonoids (221.39 ± 5.70 μg GAEq/1 g and 66.86 ± 3.36 μg CAEq/1 g, respectively) in the leaf extract. UPLC-DAD-ESI-QTOF-MS profiling showed the presence of myrecitin-3-galactoside, myrecitin-3-gluctoside, myrecitin-3-xyloside, quercetin-3- galactoside, quercetin-3-glucoside, quercetin-3-arabinofuranoside, and quercetin-3-rhamnoside. DPPH assay of the leaf extract yielded a half-maximal effective concentration (EC50) value of 125.60 ± 1.87 μg. A. spinosa L. leaves exhibited antibacterial activity against Gram (+) and Gram (-) bacteria, with particularly marked activity against B. subtilis (inhibition zone, 16 mm). Cytotoxicity data showed that the extract inhibited the proliferation of PC3 cells (IC50 ~ 600 μg).Conclusion: A. spinosa L. leaf extract is rich in valuable biologically active compounds and could represent a new resource for natural and preventive therapies.Keywords: Argania spinosa, Polyphenols, Flavonoids, Antioxidant, Antibacterial, Cytotoxi

Antimicrobial and Antibiofilm Activity of UP-5, an Ultrashort Antimicrobial Peptide Designed Using Only Arginine and Biphenylalanine

The recent upsurge of multidrug resistant bacteria (MDRB) among global communities has become one of the most serious challenges facing health professionals and the human population worldwide. Cationic ultrashort antimicrobial peptides (USAMPs) are a promising group of molecules that meet the required criteria of novel antimicrobial drug development. UP-5, a novel penta-peptide, displayed significant antimicrobial activities against various standard and clinical isolates of MDRB. UP-5 displayed MICs values within the range of (10–15 M) and (55–65 M) against Gram-positive and Gram-negative bacteria, respectively. Furthermore, UP-5 displayed antibiofilm activity with minimum biofilm eradication concentration (MBEC) value as equal to twofold higher than MIC value. At the same inhibitory concentrations, UP-5 exhibited very low or negligible toxicity toward human erythrocytes and mammalian cells. Combining UP-5 with conventional antibiotics led to a synergistic or additive mode of action that resulted in the reduction of the MIC values for some of the antibiotics by 99.7% along a significant drop in MIC values of the peptide. The stability profile of UP-5 was evaluated in full mouse plasma and serum with results indicating a more stable pattern in plasma. The present study indicates that USAMPs are promising antimicrobial agents that can avoid the negative characteristics of conventional antimicrobial peptides. Additionally, USAMPs exhibit good to moderate activity against MDRB, negligible toxicity, and synergistic outcomes in combination with conventional antimicrobial agents

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

The design and synthesis of a new lead against tuberculosis

It is estimated that one-third of the world's population has been exposed to the tuberculosis bacterium; killing eight million every year. Since the 1960s there have been no new drugs marketed, which is primarily due to the Mycobacterium tuberculosis bacilli having a complex cell wall structure, intracellular existence in the host and its ability to stay dormant for extended periods.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Computational fragment-based drug design of potential Glo-I inhibitors

AbstractIn this study, a fragment-based drug design approach, particularly de novo drug design, was implemented utilising three different crystal structures in order to discover new privileged scaffolds against glyoxalase-I enzyme as anticancer agents. The fragments were evoluted to indicate potential inhibitors with high receptor affinities. The resulting compounds were served as a benchmark for choosing similar compounds from the ASINEX® database by applying different computational ligand-based drug design techniques. Afterwards, the selection of potential hits was further aided by various structure-based approaches. Then, 14 compounds were purchased, and tested in vitro against Glo-I enzyme. Of the tested 14 hits, the biological screening results showed humble activities where the percentage of Glo-I inhibition ranged from 0–18.70 %. Compound 19 and compound 28, whose percentage of inhibitions are 18.70 and 15.80%, respectively, can be considered as hits that need further optimisation in order to be converted into lead-like compounds

A3, a Scorpion Venom Derived Peptide Analogue with Potent Antimicrobial and Potential Antibiofilm Activity against Clinical Isolates of Multi-Drug Resistant Gram Positive Bacteria

Current research in the field of antimicrobials is focused on developing novel antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they display several attractive features suitable for antimicrobial activity, including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that belongs to the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displayed significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was synthetically modified from AamAP1 in order to enhance its activity and toxicity profile. The design strategy depended on modifying the amino acid sequence of AamAP1 in order to alter its net positive charge, percentage helicity and modify other parameters that are involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 managed to selectively inhibit the growth of a wide range of resistant strains of Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics caused a synergistic antimicrobial behavior that resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. At the concentrations needed to inhibit bacterial growth, A3 displayed minimal mammalian cell toxicity. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics could provide researchers in the antimicrobial drug development field with a potential alternative for conventional antibiotics against MDR bacteria

The practice of defensive medicine among Jordanian physicians: A cross sectional study.

BackgroundDefensive medicine (DM) is a deviation from medical practice that is induced primarily by a threat of liability. While the DM behavior is well studied in the developed countries, little is known in developing countries and never been evaluated in Jordan.ObjectiveTo evaluate the prevalence of DM practice in Jordan among physicians and to investigate reasons behind its practice and potential strategies to alleviate this practice.MethodsIn this Cross-sectional study, self-administered questionnaire was distributed to a sample of physicians in both public and private sectors in Jordan. The collection period was from Jan 2021 to June 2021. The prevalence of DM practice was estimated among the study sample. Frequency scores of different DM behaviors, reasons of DM behaviors, and effectiveness of strategies in changing DM behaviors were summarized as average frequency scores with standard deviations. Multivariable linear regression models were conducted to evaluate potential predictors of total assurance and avoidance behavior scores.ResultsA total of 175 Jordanian physicians completed the survey. The prevalence of adopting (or witnessing) DM behaviors among the study sample was 68% (n = 119). Diagnostic laboratory exams followed by prescribed medications were the most practiced behaviors in excessive rate during a typical working week. Unfavorable legislation for the physician was reported as the headmost reason for practicing DM, followed by pressure from the public and mass media opinion. Continuous update of knowledge, abilities, and performance and following specific protocols and/or appropriate clinical evidence and appropriate multidisciplinary and multi-professional communication were the most effective strategies that can mitigate DM behaviors.ConclusionsDefensive medicine practice is common among Jordanian physicians with concerns about increasing pattern in the future