In Silico and In vitro Analysis of Phenolic Acids for Identification of Potential DHFR Inhibitors as Antimicrobial and Anticancer Agents.

BACKGROUND: DHFR is an indispensable enzyme required for the survival of almost all prokaryotic and eukaryotic cells, making it an attractive molecular target for drug design. OBJECTIVE: In this study, a combined in silico and in vitro approach was utilized to screen out potential anticancer and antimicrobial agents by using DHFR PDB ID 2W9S (for antimicrobial) and 1U72 (for anticancer). METHODS: Computational work was performed using Maestro Schrodinger Glide software. The DHFR inhibitory activity of the selected compounds was assessed using the DHFR test kit (CS0340-Sigma- Aldrich). RESULTS: Exhaustive analysis of in silico results revealed that some natural phenolic acids have a good docking score when compared to standards, i.e., trimethoprim and methotrexate, and have astonishing interactions with crucial amino acid residues available in the binding pocket of DHFR, such as Phe 92, Asp 27, Ser 49, Asn 18, and Tyr 98. In particular, digallic acid and chlorogenic acid have amazing interactions with docking scores of -9.9 kcal/mol and -9.6 kcal/mol, respectively, for the targeted protein 2W9S. Docking scores of -10.3 kcal/mol and -10.2 kcal/mol, respectively, for targeted protein 1U72. The best hits were then tested in vitro to evaluate the DHFR inhibitory activity of the compounds. DHFR inhibition activity results are in correlation with molecular docking results. CONCLUSION: In silico and in vitro results confirmed the good binding and inhibitory activity of some phenolic acids to the modeled target proteins. Among all the studied natural phenolic acids, chlorogenic acid, digallic acid, and rosmarinic acid appeared to be the most potential leads for future chemical alteration. This study can provide significant speculative guidance for the design and development of potent DHFR inhibitors in the future by using these compounds as leads.

In silico design of novel bioactive molecules to treat breast cancer with chlorogenic acid derivatives: a computational and SAR approach.

Introduction: Cancer is a vast group of diseases comprising abnormal cells that multiply and grow uncontrollably, and it is one of the top causes of death globally. Several types of cancers are diagnosed, but the incidence of breast cancer, especially in postmenopausal women, is increasing daily. Chemotherapeutic agents used to treat cancer are generally associated with severe side effects on host cells, which has led to a search for safe and potential alternatives. Therefore, the present research has been conducted to find novel bioactive molecules to treat breast cancer with chlorogenic acid and its derivatives. Chlorogenic acid was selected because of its known activity in the field. Methods: Several chlorogenic acid derivatives were subjected to computational studies such as molecular docking, determination of absorption, distribution, metabolism, and excretion (ADME), druglikeness, toxicity, and prediction of activity spectra for substances (PASS) to develop a potential inhibitor of breast cancer. The Protein Data Bank (PDB) IDs used for docking purposes were 7KCD, 3ERT, 6CHZ, 3HB5, and 1U72. Result: Exhaustive analysis of results has been conducted by considering various parameters, like docking score, binding energy, types of interaction with important amino acid residues in the binding pocket, ADME, and toxicity data of compounds. Among all the selected derivatives, CgE18, CgE11, CgAm13, CgE16, and CgE9 have astonishing interactions, excellent binding energy, and better stability in the active site of targeted proteins. The docking scores of compound CgE18 were -11.63 kcal/mol, -14.15 kcal/mol, and -12.90 kcal/mol against breast cancer PDB IDs 7KCD, 3HB5, and 1U72, respectively. The docking scores of compound CgE11 were -10.77 kcal/mol and -9.11 kcal/mol against breast cancer PDB IDs 3ERT and 6CHZ, respectively, whereas the docking scores of epirubicin hydrochloride were -3.85 kcal/mol, -6.4 kcal/mol, -8.76 kcal/mol, and -10.5 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5. The docking scores of 5-fluorouracil were found to be -5.25 kcal/mol, -3.43 kcal/mol, -3.73 kcal/mol, and -5.29 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5, which indicates the designed compounds have a better docking score than some standard drugs. Conclusion: Taking into account the results of molecular docking, drug likeness analysis, absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation, and PASS, it can be concluded that chlorogenic acid derivatives hold promise as potent inhibitors for the treatment of breast cancer.

Polyphenols: Natural Preservatives with Promising Applications in Food, Cosmetics and Pharma Industries; Problems and Toxicity Associated with Synthetic Preservatives; Impact of Misleading Advertisements; Recent Trends in Preservation and Legislation.

The global market of food, cosmetics, and pharmaceutical products requires continuous tracking of harmful ingredients and microbial contamination for the sake of the safety of both products and consumers as these products greatly dominate the consumer's health, directly or indirectly. The existence, survival, and growth of microorganisms in the product may lead to physicochemical degradation or spoilage and may infect the consumer at another end. It has become a challenge for industries to produce a product that is safe, self-stable, and has high nutritional value, as many factors such as physical, chemical, enzymatic, or microbial activities are responsible for causing spoilage to the product within the due course of time. Thus, preservatives are added to retain the virtue of the product to ensure its safety for the consumer. Nowadays, the use of synthetic/artificial preservatives has become common and has not been widely accepted by consumers as they are aware of the fact that exposure to preservatives can lead to adverse effects on health, which is a major area of concern for researchers. Naturally occurring phenolic compounds appear to be extensively used as bio-preservatives to prolong the shelf life of the finished product. Based on the convincing shreds of evidence reported in the literature, it is suggested that phenolic compounds and their derivatives have massive potential to be investigated for the development of new moieties and are proven to be promising drug molecules. The objective of this article is to provide an overview of the significant role of phenolic compounds and their derivatives in the preservation of perishable products from microbial attack due to their exclusive antioxidant and free radical scavenging properties and the problems associated with the use of synthetic preservatives in pharmaceutical products. This article also analyzes the recent trends in preservation along with technical norms that regulate the food, cosmetic, and pharmaceutical products in the developing countries.

Volumetric changes in pharyngeal airway in Class II division 1 patients treated with Forsus-fixed functional appliance: A three-dimensional cone-beam computed tomography study.

OBJECTIVE: Recent years have witnessed a renewed interest to determine a quantifiable relationship between mandibular advancement performed with an orthodontic appliance and the resulting airway volume. The study was conducted to evaluate the volumetric changes in pharyngeal airway space using cone-beam computed tomography (CBCT) in Class II division 1 patients with retrognathic mandible treated by Forsus-fixed functional appliance and to compare them with their pretreatment findings. MATERIALS AND METHODS: Thirty patients with Class II division 1 malocclusion of age group 10-17 years were selected randomly and evaluated for changes in pharyngeal airway volume with and without Forsus-fixed functional appliance. Patients in each group underwent CBCT scan of head and neck region at pretreatment stage and 6 months after the initial scan. Institutional approval for the project was obtained from the Ethical Committee. Volumetric changes of upper (oropharynx) and lower (hypopharynx) pharyngeal airways were measured on scanogram using computer software and intragroup comparisons were done. RESULTS: There was a statistically significant increase in the volume of both hypopharynx and oropharynx and also total airway volume in patients treated with Forsus-fixed functional appliance. Three-dimensional reconstruction of the airway also demonstrates a considerable increase in pharyngeal airway space. CONCLUSION: Forsus-fixed functional appliance can be a promising appliance for improving pharyngeal airway volume in Class II division 1 patients with retrognathic mandible thus preventing obstructive sleep apnea and other respiratory problems in future. However, the long-term implications of this treatment modality need further consideration and a longer period of follow-up.

Informed consent for braces.

The influence of law on the orthodontic profession has greatly increased in the last few decades. Dental law has emerged today as a full-fedged specialty dealing with a variety of areas, like professional negligence, doctor-patient contracts, consumer protection laws, ethics, general and special health legislations and practice regulatory mechanisms. This article highlights the concept of informed consent which is based on the premise that each individual has a right to make decisions concerning his health, disease and treatment. How to cite this article: Jharwal V, Trehan M, Rathore N, Rathee P, Agarwal D, Mathur N. Informed Consent for Braces. Int J Clin Pediatr Dent 2014;7(2):105-108.

Comparison of the Reliability of Anatomic Landmarks based on PA Cephalometric Radiographs and 3D CT Scans in Patients with Facial Asymmetry.

INTRODUCTION: Conventional cephalometry is an inexpensive and well-established method for evaluating patients with dentofacial deformities. However, patients with major deformities and in particular asymmetric cases are difficult to evaluate by conventional cephalometry. Reliable and accurate evaluation in the orbital and midfacial region in craniofacial syndrome patients is difficult due to inherent geometric magnification, distortion and the superpositioning of the craniofacial structures on cephalograms. Both two- and three-dimensional computed tomography (CT) have been proposed to alleviate some of these difficulties. AIMS AND OBJECTIVES: The aim of our study is to compare the reliability of anatomic cephalometric points obtained from the two modalities: Conventional posteroanterior cephalograms and 3D CT of patients with facial asymmetry, by comparison of intra- and interobserver variation of points recorded from frontal X-ray to those recorded from 3D CT. MATERIALS AND METHODS: The sample included nine patients (5 males and 4 females) with an age range of 14 to 21 years and a mean age of 17.11 years, whose treatment plan called for correction of facial asymmetry. All CT scans were measured twice by two investigators with 2 weeks separation for determination of intraobserver and interobserver variability. Similarly, all measurement points on the frontal cephalograms were traced twice with 2 weeks separation. The tracings were superimposed and the average distance between replicate points readings were used as a measure of intra- and interobserver reliability. Intra-and interobserver variations are calculated for each method and the data were imported directly into the statistical program, SPSS 10.0.1 for windows. RESULTS: Intraobserver variations of points defined on 3D CT were small compared with frontal cephalograms. The intraobserver variations ranged from 0 (A1, B1) to 0.6 mm with the variations less than 0.5 mm for most of the points. Interobserver variations of points between first and second tracings defined on PA Ceph and 3D CT were less than 1.5 mm for all the points. A direct comparison of frontal cephalometry and 3D CT using intraobserver variation for the first observer showed that 3D CT was more reliable than frontal cephalometry for 11 points. Direct comparison of frontal cephalometry and 3D CT for the second observer showed a similar tendency with 14 points significantly more reliable for 3D CT. Comparison of frontal cephalometry and 3D CT using interobserver variation for the tracings showed that 3D CT was more reliable than frontal cephalometry. SUMMARY AND CONCLUSION: The study has shown that 3D CT is consistently more accurate and reliable than conventional frontal cephalometry. Unfortunately, the cost of a computerized tomography examination is considerable; this means that, at this stage, its use by surgeons and orthodontists is a last resort.