scholarly journals In Silico Screening for Novel Leucine Aminopeptidase Inhibitors with 3,4-Dihydroisoquinoline Scaffold

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1753 ◽  
Author(s):  
Joanna Ziemska ◽  
Jolanta Solecka ◽  
Małgorzata Jarończyk
Keyword(s):  
Leucine Aminopeptidase ◽  
Three Dimensional ◽  
3D Qsar ◽  
In Vivo Studies ◽  
Statistical Parameters ◽  
Qsar Study ◽  
Lipinski’S Rule ◽  
Aminopeptidase Inhibitors

Cancers are the leading cause of deaths worldwide. In 2018, an estimated 18.1 million new cancer cases and 9.6 million cancer-related deaths occurred globally. Several previous studies have shown that the enzyme, leucine aminopeptidase is involved in pathological conditions such as cancer. On the basis of the knowledge that isoquinoline alkaloids have antiproliferative activity and inhibitory activity towards leucine aminopeptidase, the present study was conducted a study which involved database search, virtual screening, and design of new potential leucine aminopeptidase inhibitors with a scaffold based on 3,4-dihydroisoquinoline. These compounds were then filtered through Lipinski’s “rule of five,” and 25 081 of them were then subjected to molecular docking. Next, three-dimensional quantitative structure-activity relationship (3D-QSAR) study was performed for the selected group of compounds with the best binding score results. The developed model, calculated by leave-one-out method, showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 (0.997) and q2 (0.717). Further, 35 compounds were identified to have an excellent predictive reliability. Finally, nine selected compounds were evaluated for drug-likeness and different pharmacokinetics parameters such as absorption, distribution, metabolism, excretion, and toxicity. Our methodology suggested that compounds with 3,4-dihydroisoquinoline moiety were potentially active in inhibiting leucine aminopeptidase and could be used for further in-depth in vitro and in vivo studies.

scholarly journals Three-Dimensional Zirconia-Based Scaffolds for Load-Bearing Bone-Regeneration Applications: Prospects and Challenges

Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3207
Author(s):  
Kumaresan Sakthiabirami ◽  
Vaiyapuri Soundharrajan ◽  
Jin-Ho Kang ◽  
Yunzhi Peter Yang ◽  
Sang-Won Park
Keyword(s):  
Bone Regeneration ◽  
Biological Activities ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
High Mechanical Strength ◽  
Real World Applications ◽  
3D Fabrication ◽  
Dental Applications

The design of zirconia-based scaffolds using conventional techniques for bone-regeneration applications has been studied extensively. Similar to dental applications, the use of three-dimensional (3D) zirconia-based ceramics for bone tissue engineering (BTE) has recently attracted considerable attention because of their high mechanical strength and biocompatibility. However, techniques to fabricate zirconia-based scaffolds for bone regeneration are in a stage of infancy. Hence, the biological activities of zirconia-based ceramics for bone-regeneration applications have not been fully investigated, in contrast to the well-established calcium phosphate-based ceramics for bone-regeneration applications. This paper outlines recent research developments and challenges concerning numerous three-dimensional (3D) zirconia-based scaffolds and reviews the associated fundamental fabrication techniques, key 3D fabrication developments and practical encounters to identify the optimal 3D fabrication technique for obtaining 3D zirconia-based scaffolds suitable for real-world applications. This review mainly summarized the articles that focused on in vitro and in vivo studies along with the fundamental mechanical characterizations on the 3D zirconia-based scaffolds.

scholarly journals The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Evaluation ◽  
Three Dimensional ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Murine Models ◽  
In Vivo Experiments ◽  
Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

scholarly journals Docking against Lung cancer protein and Drug-likeliness of Bioactive Compounds from Phymatosorus scolopendria (Burm.F.) Pic. Serm.

2020 ◽  
pp. 437-441
Author(s):  
Sujatha Srinivasan ◽  
Catharin S. Sivaraman ◽  
Ramya R. Issac ◽  
Gayathiri Mahalingam ◽  
Gnana D. R. Roke
Keyword(s):  
Lung Cancer ◽  
Bioactive Compounds ◽  
Vinyl Ester ◽  
In Vivo Studies ◽  
Lipinski’S Rule ◽  
Lipinski’S Rule Of Five ◽  
Gas Chromatography Mass Spectroscopy ◽  
Nitrophenyl Ester

Phymatosorus scolopendria (Burm.F.) Pic. Serm. is a medicinally important fern which is used traditionally by various people all over the World. The aim of this research focuses on the docking against lung cancer protein (2ITO) with bioactive compounds of Phymatosorus scolopendria (Burm.F.) Pic. Serm. which is obtained by using Gas Chromatography Mass Spectroscopy.  The same compounds were analysed using Lipinski’s rule of five for its pharmacological prediction. The bioactive compounds were further referred for ADMET property to find its pharmacokinetic potency and prediction towards its potential as drug in future.   Among the four compounds docked with the Lung cancer protein (2ITO) 4-Nitrophenyl laurate shows high docking score followed by Hexadecanoic acid, 4 Nitrophenyl ester and Myristic acid Vinyl ester. Out of four compounds studied three compounds satisfied the  drug-likeliness based on Lipinski’s rule of five. The present work suggests the bioactive compounds of Phymatosorus scolopendria (Burm.F.) Pic. Serm.  for further in vitro and in vivo studies for its anticancer benefits especially related to lung cancer.

FORMULATION, OPTIMIZATION AND EVALUATION OF MOXIFLOXACIN HYDROCHLORIDE GASTRO RETENTIVE TABLETS

INDIAN DRUGS ◽  
2021 ◽  
Vol 58 (01) ◽  
pp. 79-84
Author(s):  
Raghavendra K. Gunda ◽  
◽  
A. Vijayalakshmi ◽  
K. Masilamani ◽  
◽  
...  
Keyword(s):  
Fickian Diffusion ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Wet Granulation ◽  
Statistical Parameters ◽  
Compression Technique ◽  
Ich Guidelines ◽  
Gastro Retentive

The objective of the current study was to develop gastro retentive formulation of moxifloxacin. HCl using various drug release modifiers and performing in vitro and in in vivo evaluations. Moxifloxacin is a novel synthetic fluoro quinolone antibacterial agent. Floating, muco adhesive tablets of moxifloxacin. HCl were prepared using variable amounts of HPMCK100M, Lannea coromandelica gum by direct compression technique and wet granulation technique, respectively. Formulations were developed, optimized and checked for pharmacopoeial tests. Results show that all the batches lie within the standard limits. Dissolution parameters of all formulations were sy=ubjected to kinetic fitting and various statistical parameters were determined. Formulation (FS5 ) containing 50 mg of HPMCK100M and 50 mg of LCG, is the best formulation showing similarity f2 =71.734, f1 = 4.271 with the marketed product (Avelox). It follows Higuchi's kinetics, non-fickian diffusion first order kinetics(n=0.717). In vivo studies were performed for the FS5 with 6 healthy rabbits and pharmacokinetic parameters were determined, compared with Avelox and it was found that FS5 produced similar results. Stability studies were performed for FS5 as per ICH guidelines. Results were found to be satisfactory. FS5 is expected to improve patient compliance by means of providing good clinical outcome

scholarly journals Accuracy of aortic annular measurements obtained from three-dimensional echocardiography, CT and MRI: human in vitro and in vivo studies

Heart ◽  
2012 ◽  
Vol 98 (15) ◽  
pp. 1146-1152 ◽  
Author(s):  
Wendy Tsang ◽  
Michael G Bateman ◽  
Lynn Weinert ◽  
Gian Pellegrini ◽  
Victor Mor-Avi ◽  
...  
Keyword(s):  
Three Dimensional ◽  
In Vivo Studies ◽  
Dimensional Echocardiography ◽  
Three Dimensional Echocardiography ◽  
Ct And Mri

Reliability of a Seven-Segment Foot Model with Medial and Lateral Midfoot and Forefoot Segments During Walking Gait

2016 ◽  
Vol 32 (6) ◽  
pp. 608-613 ◽  
Author(s):  
Stephen C. Cobb ◽  
Mukta N. Joshi ◽  
Robin L. Pomeroy
Keyword(s):  
Time Series ◽  
Three Dimensional ◽  
In Vivo Studies ◽  
Multiple Correlation ◽  
Walking Gait ◽  
Foot Model ◽  
Stance Time ◽  
Independent Motion

In-vitro and invasive in-vivo studies have reported relatively independent motion in the medial and lateral forefoot segments during gait. However, most current surface-based models have not defined medial and lateral forefoot or midfoot segments. The purpose of the current study was to determine the reliability of a 7-segment foot model that includes medial and lateral midfoot and forefoot segments during walking gait. Three-dimensional positions of marker clusters located on the leg and 6 foot segments were tracked as 10 participants completed 5 walking trials. To examine the reliability of the foot model, coefficients of multiple correlation (CMC) were calculated across the trials for each participant. Three-dimensional stance time series and range of motion (ROM) during stance were also calculated for each functional articulation. CMCs for all of the functional articulations were ≥ 0.80. Overall, the rearfoot complex (leg–calcaneus segments) was the most reliable articulation and the medial midfoot complex (calcaneus–navicular segments) was the least reliable. With respect to ROM, reliability was greatest for plantarflexion/dorsiflexion and least for abduction/adduction. Further, the stance ROM and time-series patterns results between the current study and previous invasive in-vivo studies that have assessed actual bone motion were generally consistent.

scholarly journals In vitro 3D Spheroid Culture Developed on the Parafilm Surface Using HEK-293 Cells

2020 ◽  
Vol 3 (1) ◽  
pp. 220-227
Author(s):  
Erdal Eroğlu
Keyword(s):  
Three Dimensional ◽  
Culture Method ◽  
In Vivo Studies ◽  
Preclinical Research ◽  
Hek 293 ◽  
Hek 293 Cells ◽  
293 Cells ◽  
Hanging Drop Culture

Preclinical research to predict the effects of drugs and chemicals on humans is commonly carried out either by cell culture studies in vitro condition or on animals in vivo condition. While drug studies tested on cells cultured as a monolayer in plastic flasks are incompatible with realistic results, falsifying findings can also be achieved from in vivo studies performed on different species. In recent years, research on drug tests using spheroid cultures formed by growing cells in three-dimensional (3D) in vitro has attracted great interest. 3D spheroid structures are formed by growing the cells in a drop suspended on superhydrophobic surfaces. In this study, HEK-293 cells were investigated on parafilm surfaces displaying superhydrophobic properties by growing in 2 µl volume using hanging drop culture method in terms of spheroid formation. Light microscopy images from spheroid structures were taken on different incubation days and the area of spheroids was measured using the ImageJ program. Our study holds important findings for a chip platform that can be developed for use in vitro drug tests.

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