Amal G. Al-Bakri

The assessment of the antibacterial and antifungal activities of aspirin, EDTA and aspirin–EDTA combination and their effectiveness as antibiofilm agents

Aims:  To evaluate the antimicrobial activities of aspirin, EDTA and an aspirin‐EDTA (A‐EDTA) combination against Pseudomonas aeruginosa, Escherichia coli and Candida albicans in planktonic and biofilm cultures.

The epidemiology and molecular characterization of methicillin-resistant staphylococci sampled from a healthy Jordanian population.

The prevalence of natural carriage and molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) isolates in a Jordanian community were investigated. The MRSA nasal carriage rate in 227 healthy volunteers was 7·5% and the majority (81%) of MRSA harboured the resistance element SCCmec type IVe and were of a novel spa type t9519 (76%); other significant spa gene types were t223 (14·7%) and t044 (5·9%). All MRSA isolates were susceptible to other classes of antibiotics, and tested positive for at least three virulence factor encoding genes, but only two harboured the pvl gene. MR-CoNS carriage was 54·2% and these isolates were characterized by single, double and untypable SCCmec elements, with Staphylococcus epidermidis SCCmec type IVa predominating. Of eight subjects with nasal co-colonization of MR-CoNS + MRSA, three shared SCCmec type IV in both groups of organisms. This is the first report of methicillin-resistant staphylococci carriage in a Jordanian community and its findings are important for epidemiological study and infection control measures of these organisms.

In Silico Screening for Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors Using Physicochemical Filters and High-Throughput Docking Followed by In Vitro Evaluation

Reverse transcriptase, being the pivot in human immunodeficiency virus replication, is one of the most attractive targets for the development of new antiretroviral agents. We applied a virtual screening workflow based on a combination of physicochemical filters with high‐throughput rigid molecular docking to discover novel efficient lead scaffolds for human immunodeficiency virus type 1 reverse transcriptase inhibition. In our protocol, different filters were employed to enrich the lead‐likeness and improve the ligands efficiency of the filtered compounds. Out of the 238 819 compounds included in the Natinal Cancer Institute database, 500 virtual screening hits were retrieved employing filter and fred (molecular docking engine) softwares. Four compounds from the 20 highest ranking scored hits tested positive in human immunodeficiency virus type 1 reverse transcriptase using non‐radioactive colorimetric assay method. These results demonstrate that our virtual screening protocol is able to enrich novel scaffolds for human immunodeficiency virus type 1 reverse transcriptase inhibition that could be useful for drug development in the area of acquired immune‐deficiency syndrome treatment.

Determination of the antibiofilm, antiadhesive, and anti-MRSA activities of seven Salvia species

Background: Several Salvia species are indigenous to Jordan and are widely used as beverages and spices and for their medicinal properties. The objective of the study was to establish the antimicrobial activities, including the antiadhesive and antibiofilm effects of seven different Salvia species. Materials and Methods: Methods used for planktonic culture included agar diffusion, broth microdilution, and minimal biocidal concentration determination while viable count was used for the determination of the antibiofilm and antiadhesion activities. Overnight cultures of reference strains of Candida albicans, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and clinical strains of methicillin-resistant S. aureus (MRSA) were used as test microorganisms. Results: An antimicrobial activity toward planktonic cultures demonstrated a significant bacteriocidal activity (≥4 log cycle reduction) for the S. triloba extract against S. aureus including MRSA. Its volatile oil exhibited an antimicrobial activity covering all tested microorganisms with the exception of P. aeruginosa. S. triloba extract and volatile oil were successful in preventing and controlling the biofilm, demonstrating antiadhesion and antibiofilm activities, respectively. Conclusion: These reported activities for S. triloba extract and volatile oil allows their listing as potential antibiofilm and anti-MRSA natural agents. This might suggest their use as an antiseptic in the prophylaxis and treatment of S. aureus-associated skin infections. The antimicrobial activity of the other tested Salvia species was negligible.

Discovery of New Antifungal Leads via Pharmacophore Modeling and QSAR Analysis of Fungal N‐Myristoyl Transferase Inhibitors Followed by In Silico Screening

N‐Myristoyl transferase is an essential enzyme for fungal growth and survival. The continuous interest in the development of new antifungal agents prompted recent interest in developing new potent inhibitors of fungal N‐myristoyl transferase. In this context, we combined pharmacophore and QSAR modeling to explore the structural requirements for potent N‐myristoyl transferase inhibitors employing 55 known N‐myristoyl transferase ligands. Four binding pharmacophore models emerged in the optimal QSAR equations ( = 0.81–0.83, F‐statistic = 47.89–58.83,  = 0.77–0.80, against 11 external test inhibitors = 0.61–0.71). The successful pharmacophores were complemented with exclusion spheres to optimize their receiver operating characteristic curve profiles. The QSAR equations and their associated pharmacophore models were validated by the identification and experimental evaluation of new promising antifungal leads retrieved from the NCI database and our in‐house‐built database of established drugs and agrochemicals.

Major characteristics of Staphylococcus aureus colonizing Jordanian infants

Colonization of infants with methicillin‐resistant Staphylococcus aureus (MRSA) carries specific toxin genes. In particular, Panton–Valentine leukocidin (PVL) are a risk factor for subsequent infection during hospitalization. This prospective study investigated important epidemiological characteristics of Staphylococcus aureus colonizing the nares and intestines of Jordanian infants.

Preferential accumulation of gold nanorods into human skin hair follicles: Effect of nanoparticle surface chemistry

HYPOTHESIS Gold nanoparticles (GNP) are considered an ideal model to help understanding the nano-skin interface. The surface functionality of gold nanorods (GNR) is expected to influence the uptake of nanoparticles into specific targets of skin such as hair follicles or dermis. Hence, it should be possible to modify the surface chemistry of GNP to achieve more targeted and safe skin therapy. EXPERIMENTS GNR functionalized with various surface ligands (neutral, anionic, cationic, and hydrophobic) were evaluated for their accumulation into hair follicles of human skin sheets using ex-vivo setup. The extent of GNR accumulation into hair follicles and other skin compartments was quantified by inductively coupled plasma-optical emission spectroscopy (ICP-OES), and their spatial distribution through skin layers was investigated by laser ablation-inductively coupled plasma-mass spectroscopy (LA-ICP-MS). RESULTS The lipophilic properties of sebum-rich hair follicles enhanced the accumulation of hydrophobic polystyrene (PS)-GNR into hair follicles (∼13% of the total applied dose), while neutral polyethylene glycol (PEG)-GNR were distributed into all skin compartments, especially the dermis (∼11.5% of the total applied dose), which exhibits hydrophilic characteristics. Charged GNR showed a negligible percentage of penetration into any of the skin compartments. GNR could be a promising approach for targeted skin disease treatment and transdermal administration of drugs and therapy.

A prodrug approach to enhance azelaic acid percutaneous availability

Abstract Azelaic acid is a dicarboxylic acid compound used in treatment of acne vulgaris. However, high concentration (ca 20%) is needed to guarantee the drug availability in the skin. The latter increases the incidence of side effects such as local irritation. The prodrug strategy to enhance azelaic acid diffusion through skin was not reported before. Thus, a lipophilic prodrug of azelaic acid (diethyl azelate [DEA]) was synthesized and investigated to improve percutaneous availability of azelaic acid, with a subsequent full physical, chemical, and biological characterization. Expectedly, DEA exhibited a significant increase in diffusion compared to azelaic acid through silicone membrane. In contrast, the diffusion results through human stratum corneum (SC) displayed weaker permeation for DEA with expected retention in the SC. Therefore, a desorption study of DEA from SC was conducted to examine the reservoir behavior in SC. Results showed an evidence of sustained release behavior of DEA from SC. Consequently, enhancement of keratolytic effect is expected due to azelaic acid produced from enzymatic conversion of DEA released from SC.

Synthesis, Antibacterial Evaluation and QSAR of α-Substituted-N4-Acetamides of Ciprofloxacin and Norfloxacin

Twenty six α-substituted N4-acetamide derivatives of ciprofloxacin (CIPRO) and norfloxacin (NOR) were synthesized and assayed for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Bacillus subtilis. The derivatives were primarily more active against Gram-positive bacteria. The CIPRO derivatives, CD-7 (Ar = 3-chlorophenyl), CD-9 (Ar = 2-pyrimidyl) and CD-10 (α-phenyl, Ar = 2-pyrimidyl), exhibited lower MIC values, 0.4–0.9 μM, against Staphylococcus aureus than CIPRO, while only compound CD-10 exhibited better activity, 0.1 μM, against Bacillus subtilis than CIPRO. In addition, compounds CD-5 (Ar = 2-methoxyphenyl), CD-6 (α-phenyl, Ar = 2-methoxyphenyl), CD-7 (Ar = 3-Chlorophenyl), CD-8 (α-phenyl, Ar = 3-chlorophenyl) and CD-9 (Ar = 2-pyrimidyl) showed MIC values below 1.0 μM against this strain. The NOR derivatives showed lower activity than NOR itself against Staphylococcus aureus, although ND-6 (α-phenyl, Ar = 2-methoxyphenyl) and ND-7 (Ar = 3-chlorophenyl) showed MIC values less than 2 μM. Two NOR derivatives, ND-7 and ND-6, exhibited MIC values of 0.7 and 0.6, respectively, which were comparable to that of NOR against Bacillus subtilis, while compounds ND-8 (α-phenyl, Ar = 3-chlorophenyl) and ND-10 (α-phenyl, Ar = 2-pyrimidyl) exhibited MIC values less than 1.0 μM against the same strain. QSAR revealed that while polarity is the major contributing factor in the potency against Staphylococcus aureus, it is balanced by lipophilicity and electron density around the acetamide group. On the other hand, electron density around the introduced acetamide group is the major determining factor in the activity against Bacillus subtilis, with a lesser and variable effect for lipophilicity.

Evaluation of paromomycin sulphate permeation using ex vivo human skin model

Abstract Ex vivo evaluation of drug release and skin permeation from topical formulations of antileishmanial drug paromomycin sulphate was carried out using intact full thickness human skin. Potency-based microbiological assay was used for the analysis of paromomycin concentrations. A total percentage drug recovery of 86 ± 26% was obtained. Incubation periods of 1 and 3 h resulted in percentage drug permeation into deep skin layers ranging from 1.3 ± 0.04% to 5.3 ± 2.0% with paraffin-based ointment and from 1.6 ± 0.8% to 3.9 ± 1% with microemulsion-based emulgel. Although a small percentage, this is still significantly higher than those previously reported using animal skin models.