Noha A. Saleh

Structural and electronic properties of new fullerene derivatives and their possible application as HIV-1 protease inhibitors.

Density functional theory (DFT) calculations have been carried out at the hybrid Becke 3-Lee-Yang-Parr; B3LYP/3-21G** level of theory to study two series of hydroxy-chalca-acetic acid-(4-pyrrolidin-1-yl-phenyl) ester [C(60)-C(2)H(4)N-(4-XCOCH(2)OH)C(6)H(4)] and hydroxy-chalcoacetic acid-[2-(2-hydroxy-acetylchalcanyl)-4-pyrrolidin-1-yl-phenyl] ester[C(60)-C(2)H(4)N-(3,4-XCOCH(2)OH)C(6)H(4)]. The X atom is O, S or Se for the two series. The vibrational spectra, physical, chemical, thermodynamics and Quantitative Structure Activity Relationship (QSAR) properties of the studied molecules are calculated and discussed. We have evaluated these molecules as HIV-1 protease inhibitors based on the hydrogenation interaction between the hydroxymethylcarbonyl (HMC) groups and the two aspartic acid of the HIV-1 protease active site. Results show that some of the investigated fullerene-based derivatives can be considered promising as HIV-1 protease inhibitors.

The QSAR and docking calculations of fullerene derivatives as HIV-1 protease inhibitors.

The inhibition of HIV-1 protease is considered as one of the most important targets for drug design and the deactivation of HIV-1. In the present work, the fullerene surface (C60) is modified by adding oxygen atoms as well as hydroxymethylcarbonyl (HMC) groups to form 6 investigated fullerene derivative compounds. These compounds have one, two, three, four or five O atoms+HMC groups at different positions on phenyl ring. The effect of the repeating of these groups on the ability of suggested compounds to inhibit the HIV protease is studied by calculating both Quantitative Structure Activity Relationship (QSAR) properties and docking simulation. Based on the QSAR descriptors, the solubility and the hydrophilicity of studied fullerene derivatives increased with increasing the number of oxygen atoms+HMC groups in the compound. While docking calculations indicate that, the compound with two oxygen atoms+HMC groups could interact and binds with HIV-1 protease active site. This is could be attributed to the active site residues of HIV-1 protease are hydrophobic except the two aspartic acids. So that, the increase in the hydrophilicity and polarity of the compound is preventing and/or decreasing the hydrophobic interaction between the compound and HIV-1 protease active site.

Platelet-rich plasma for resistant oral erosions of pemphigus vulgaris: A pilot study

Oral erosions and ulcers of pemphigus vulgaris (PV) are a debilitating condition that is usually difficult to treat. The wound healing properties of platelet‐rich plasma (PRP) encouraged us to evaluate its usefulness in treatment of non‐healing oral PV lesions. Seven patients with chronic oral PV, resistant to conventional therapy, were treated with weekly to monthly injections of PRP of affected mucosal membranes. All recruits reported improvement in pain and mastication and 6 of 7 patients had an improvement in pemphigus disease area index scores with PRP treatment. PRP injections seems to accelerate the healing process and decrease the pain and eating discomfort associated with the oral erosions and ulcers induced by PV.

QSAR Analysis and Molecular Docking Simulation of Suggested Peptidomimetic NS3 Protease Inhibitors

Based on the N-terminal hexapeptide product of hydrolysis (EDVVCC) at HCV NS5A/5B junction, three modified groups of compounds are built. The first group contains linear peptides while the second and third groups contain P1-P3 and P2-P4 macrocyclic structures, respectively. Quantitative Structure Activity Relationship (QSAR) characterization and docking simulations are performed in order to investigate the potential of these compounds as HCV NS3/4A protease inhibitors. Based on the QSAR properties, the three most stable compounds due to their lowest total energy are P1-P3 and P2-P4 macrocycles of azahexapeptide sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azahexapeptide sequence (DDIVP norvaline). They also have high surface area, solvent accessible surface area, volume, molar refractivity and polarizabilty. They have moderately low dipole moment and good log P values, as well. The docking scores of the best two P2-P4 macrocycles are just acceptable. The two compounds 5A/5B hexapeptide sequence (DDIVP vinyl amino cyclopropane) and P2-P4 macrocycle of azapentapeptide sequence (DIVP vinyl amino cyclopropane) yielded the best docking scores.

Recent Trends on QSAR in the Pharmaceutical Perceptions

Description: Quantitative Structure-Activity Relationship (QSAR) is a field where true multidisciplinary approaches are being used. This volume titled Recent Trends on QSAR in the Pharmaceutical Perceptions offers an overview on the latest advancements in the field. The e-book explains both basic approaches and new approaches and ideas in QSAR research, providing readers with an impression of recent inclinations and advances in different aspects of the QSAR strategies, such as descriptors, methods of modeling and validation. This e-book is a valuable reference for pharmacologists, medicinal chemists, drug designers, biotechnologists and industry (pharmaceutical and chemical) professionals. It should serve as an important reference material to stimulate interactions and bridge the gap between participants in academia and industries.

Cathelicidin (LL-37) level in the scalp hair of patients with tinea capitis.

Abstract Antimicrobial peptides (AMPs) are considered an important first line of defense against pathogens. Cathelicidin LL‐37 was upregulated in response to fungal infection. In this work we aimed to evaluate cathelicidin LL‐37 in the hair of tinea capitis and compare it to normal controls. Hair samples were collected from 30 children and 30 controls aged from 2 to10 years old, and the level of cathelicidin LL‐37 in the hair was detected by quantitative real‐time PCR. The 30 patients were further subdivided into three subgroups according to their clinical type. Ten patients were scaly type, 10 patients were black dots type, and 10 patients were kerion type. Cathelicidin level in patients ranged from 6.0 to 17.5 with mean ± SD (11.3 ± 2.3) and in control ranged from 1.02 to 6.2, with mean ± SD (2.8 ± 1.5). There was a significant difference between the patients and controls regarding the cathelicidin level; P value was 0. The mean cathelicidin level was lowest in the kerion type10.73 ± 2.6 and highest in the black dot type 12.05 ± 2.76. However, there was no significant difference between the cathelicidin level of the different clinical types of tinea capitis; P value was 0.58. In conclusion, the level of cathelicidin LL‐37 in hair specimens of human tinea capitis was significantly higher than controls.

On the Molecular Modeling Analyses of Novel HIV-1 Protease Inhibitors Based on Modified Chitosan Dimer

The molecular modeling studies include quantitative structure activity relationship, IR spectra, and docking calculations, occurring for novel inhibitors based on chitosan dimer which were tried as HIV protease. The inhibitors were investigated with molecular modeling calculations at different level of theories. Each compound has phenol with hydroxymethylcarbonyl (HMC) group which added to chitosan in positions 2, 3, 2′, or 3′. The geometry of studied compounds is optimized with semiempirical PM3 method. Quantitative structure activity relationship (QSAR) properties of the suggested compounds are calculated at the same level of theory. Depending on QSAR calculations, the compounds with positions 2 and 2′ are less hydrophilic. The position 2′ compound makes good docking interaction into HIV protease active site. Calculated IR spectra indicate that the interaction through hydrogen bonding through the hydrogen of OH at positions 3 and 3′ gives rise to two OH bands one for chitosan and the other for phenol and HMC group. While at position 3′ CH band starts to appear.

Clinical and dermoscopic evaluation of combined (salicylic acid 20% and azelaic acid 20%) versus trichloroacetic acid 25% chemical peel in acne: a RCT

Abstract Background: Combined azelaic acid (AA) and salicylic acid (SA) have not been previously used for acne. Objective: To compare the efficacy of this combination versus trichloroacetic acid (TCA) 25% peel in acne. Methods: Thirty-four patients were included in this trial. Patients received four sessions 2 weeks apart. The combined solution was applied to one side of the face, while TCA was applied to the other. Our outcomes were physician-reported clinical improvement, dermoscopic assessment of the erythema and patient’s satisfaction. Results: After two sessions, a significant clinical improvement was observed in non-inflammatory lesions in the TCA-treated side-treated TCA and in inflammatory lesions in the SA/AA-treated side. At the end, both modalities led to significant improvement, with no significant difference in between. Patients reported more discomfort with the TCA-treated side. There was no significant different clinical improvement in both treated sides as regards SPT. Erythema improved in both sides. Patients were more satisfied by the SA/AA-treated side. Conclusion: Chemical peeling is effective in controlling mild–moderate acne in SPT III-IV. Combined SA 20% and AA 20% are recommended at early stage of treatment if patients have more inflammatory lesions, while TCA is recommended if patients have more non-inflammatory lesions.

Design and Development of Some Viral Protease Inhibitors by QSAR and Molecular Modeling Studies

There are many aspects to understand biological interactions. Computational methods have been of great help to solve these problems, particularly where the experiment is least feasible or very costly. The mystery of biological problems and the success of theoretical approaches to solve them have led to develop newer and newer theoretical methods, which have been largely facilitated by the development of efficient computers. They are now cheap and save time and money both to solve any problem. Results are almost verified by experiment. For biological systems, quantitative structure–activity relationship (QSAR) and molecular modeling studies have acquired the leading role. In this chapter, the application QSAR and molecular modeling approaches in the design and development of inhibitors of various viral proteases is discussed.

Structure-based drug design of novel peptidomimetic cellulose derivatives as HCV-NS3 protease inhibitors

&NA; Hepatitis C Virus (HCV) represents a global health threat not only due to the large number of reported worldwide HCV infections, but also due to the absence of a reliable vaccine for its prevention. HCV NS3 protease is one of the most important targets for drug design aiming at the deactivation of HCV. In the present work, molecular docking simulations are carried out for suggested novel NS3 protease inhibitors applied to the Egyptian genotype 4. These inhibitors are modifications of dimer cellulose by adding a hexa‐peptide to the cellulose at one of the positions 2, 3, 6, 2′, 3′ or 6′. Results show that the inhibitor compound with the hexa‐peptide at position 6 shows significantly higher simulation docking score with HCV NS3 protease active site. This is supported by low total energy value of docking system, formation of two H‐bonds with HCV NS3 protease active site residues, high binding affinity and increased stability in the interaction system.