Computer-aided discovery of antimicrobial agents as potential enoyl acyl carrier protein reductase inhibitors

Purpose: To perform a virtual screening for a set of drug-like ligand library against the Staphylococcus aureus enoyl acyl carrier protein reductase, saFabI.Methods: The virtual screening was conducted based on a previously validated pharmacophoreconstrained docking. Consequently, the top list obtained was filtered using visual inspection where forty compounds were selected for experimental testing using disk-diffusion test and broth dilution method. The hits obtained were checked for their toxicity against human fibroblasts cell lines.Results: Three compounds were active against Staphylococcus aureus and other tested gram-positive bacteria. However, no significant inhibitory activity (p < 0.05) was detected against Escherichia coli or Candida albicans. The minimum inhibitory concentration (MIC) values for the most active compounds were identified using the broth dilution method; all of them exhibited inhibitory activity within micromolar range.The docking results showed that the hits obtained exhibited a small size with a nice binding mode to saFabI enzyme, forming the important interactions with the key residues. Furthermore, the best three hits demonstrated good safety profile as they did not show any significant toxicity against human fibroblast cell line.Conclusion: Overall, the newly discovered hits can act as a good starting point in the future for the development of safe and potent antibacterial agents.Keywords: Enoyl acyl carrier protein reductase, saFabI, Antibacterial agents, Docking, Constraint, Virtual screening Tropical Journal of Pharmaceutica

Acute toxicity of essential oils of two Moroccan endemic species: Thymus broussonetii and Thymus leptobotrys

Abstract Thymus species essential oils are widely used in aromatherapy to treat several ailments. However, there is no report on their safety. In this study, we propose to investigate the acute toxicity of T. leptobotrys and T. broussonetii essential oils. These two species were selected on the basis of their frequency of medicinal use and commercial importance. Chemical analysis of these two species essential oil revealed that thymol, borneol, carvacrol and p-cymene were the main chemical constituents in T. broussonetii, whereas the essential oil of T. leptobotrys contains carvacrol (98 %) as the major component. In the acute toxicity assay, the animals showed no stereotypical symptoms associated with toxicity such as convulsion, ataxy, diarrhoea or increased diuresis. The calculated median lethal dose (LD 50 ) was estimated at 4.47 g/kg for T. broussonetii and 2.66 g/kg for T. leptobotrys

Evaluation of functional dynamics during osseointegration and regeneration associated with oral implants

The aim of this paper is to review current investigations on functional assessments of osseointegration and assess correlations to the peri-implant structure.The literature was electronically searched for studies of promoting dental implant osseointegration, functional assessments of implant stability, and finite element (FE) analyses in the field of implant dentistry, and any references regarding biological events during osseointegration were also cited as background information.Osseointegration involves a cascade of protein and cell apposition, vascular invasion, de novo bone formation and maturation to achieve the primary and secondary dental implant stability. This process may be accelerated by alteration of the implant surface roughness, developing a biomimetric interface, or local delivery of growth-promoting factors. The current available pre-clinical and clinical biomechanical assessments demonstrated a variety of correlations to the peri-implant structural parameters, and functionally integrated peri-implant structure through FE optimization can offer strong correlation to the interfacial biomechanics.The progression of osseointegration may be accelerated by alteration of the implant interface as well as growth factor applications, and functional integration of peri-implant structure may be feasible to predict the implant function during osseointegration. More research in this field is still needed. To cite this article: Chang P-C, Lang NP, Giannobile WV. Evaluation of functional dynamics during osseointegration and regeneration associated with oral implants. Clin. Oral Impl. Res . 21 , 2010; 1–12.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78668/1/j.1600-0501.2009.01826.x.pd

System reliability-redundancy optimization with cold-standby strategy by an enhanced nest cuckoo optimization algorithm

Three main ways can be followed to design for system reliability, namely component reliability allocation, redundancy allocation (active or standby) and reliability-redundancy allocation. Standby redundancy provides higher reliability than the active one, but its modelling is more complicated. This paper considers the system reliability-redundancy allocation with cold-standby strategy and proposes a new approach to its solution, called enhanced nest cuckoo optimization algorithm (ENCOA). ENCOA uses more realistic procedures than the cuckoo optimization algorithm (COA) in terms of egg laying and survivor cuckoos, based on advanced studies of the European cuckoo's lifestyle available in the literature. Four case studies are investigated in order to highlight the applicability and the performance of the proposed approach. The results are compared to those obtained in previous works of literature

Multi-objective availability and cost optimization by PSO and COA for series-parallel systems with subsystems failure dependencies

System availability and cost are two of the elements of system dependability. Most systems involve subsystems with failure dependencies. The failure dependencies complicate the optimization of those elements. In this paper, the multi-objective optimization problem of availability and cost is addressed for series-parallel systems with subsystems failure dependencies in case of strong dependency. The problem is solved by applying the particle swarm optimization (PSO) algorithm and the cuckoo optimization algorithm (COA). The multi-objective optimization problem is converted to a single one using the weighted-sum method. The results of a system consisting of six subsystems are analyzed with a comparison of the methods. The best value of the system availability and cost, number of function evaluations, CPU time, and standard deviation reveal that the COA has outperformed the PSO