RESUMEN
Cancer is one of the most prominent causes of death worldwide and tubulin is a crucial protein of cytoskeleton that maintains essential cellular functions including cell division as well as cell signalling, that makes an attractive drug target for cancer drug development. 1,3,4-oxadiazoles disrupt microtubule causing G2-M phase cell cycle arrest and provide anti-proliferative effect. In this study, field-based 3D-QSAR models were developed using 62 bioactive anti-tubulin 1,3,4-oxadiazoles. The best model characterized by PLS factor 7 was rigorously validated using various statistical parameters. Generated 3D-QSAR model having high degree of confidence showed favourable and unfavourable contours around 1,3,4-oxadiazole core that assisted in defining proper spatial positioning of desired functional groups for better bioactivity. A five featured pharmacophore model (AAHHR_1) was developed using same ligand library and validated through enrichment analysis (BEDROC160.9 value = 0.59, Average EF 1% = 27.05, and AUC = 0.74). Total 30,212 derivatives of 1,3,4-oxadiazole obtained from PubChem database was prefiltered through validated pharmacophore model and docked in XP mode on binding cavity of tubulin protein (PDB code: 1SA0) which led into the identification of 11 HITs having docking scores between -7.530 and -9.719 kcal/mol while the reference compound Colchicine exerted docking score of -7.046 kcal/mol. Following the analysis of MM-GBSA and ADME studies, HIT1 and HIT4 emerged as the two promising hits. To verify their thermodynamic stability at the target site, molecular dynamic simulations were carried out. Both HITs were further subjected to DFT analysis to determine their HOMO-LUMO energy gap for ensuring their biological feasibility. Finally, molecular docking based structural exploration for 1,3,4-oxadiazoles to set up a lead of Formula I for further advancements of tubulin polymerization inhibitors as anti-cancer agents.Communicated by Ramaswamy H. Sarma.
RESUMEN
A facile one-step catalyst free methodology has been developed for the regioselective functionalization of 4,6-diphenylpyrimidin-2(1H)-ones under mild conditions. Selectivity towards the O-regioisomer was achieved by using Cs2CO3 in DMF without use of any coupling reagents. A total of 14 regioselective O-alkylated 4,6-diphenylpyrimidines were synthesized in 81-91% yield. In the DFT studies it was observed that the transition state for the formation of the O-regioisomer is more favourable with Cs2CO3 as compared to K2CO3. Furthermore, this methodology was extended to increase the O/N ratio for the alkylation of 2-phenylquinazolin-4(3H)-one derivatives.
RESUMEN
STATEMENT OF PROBLEM: The occurrence porosity in polymethyl methacrylate, the most commonly used denture base material is a problem. The occurrence of oral candidiasis and other infections has also been reported in denture users. PURPOSE: The aim of this study was to evaluate the effect of addition of an antimicrobial agent, silver zeolite on the porosity of denture base resin, which will be an effective tool in the prevention of oral candidiasis among denture wearers. This study also aims to analyze the effect of polymerization technique on porosity in zeolite incorporated dentures to develop a denture base resin which will be easy to process with optimal mechanical and antimicrobial properties. MATERIALS AND METHODS: Eighty rectangular resin specimens (65 mm × 40 mm × 5 mm) were divided into one control group (A) and three experimental groups (B - Microwave cured denture base resin specimens, C - Conventionally cured denture base resin incorporated with antibacterial zeolites, D - Microwave cured denture base resin incorporated with antibacterial zeolites) porosity was calculated by measurement of the specimen volume before and after its immersion in water. Data were analyzed using one-way analysis of variance. RESULTS: The mean values of the percent mean porosity were: A = 0.9555%, B = 0.9590%, C = 0.9630%, D = 0.9695%. No significant differences were found in mean porosity among the groups evaluated. CONCLUSION: Within the limitations of this study, it could be concluded that the addition of zeolites did not result in significant porosity and that the use of microwave processing is a viable option for denture processing.
RESUMEN
AIM: The purpose of this study was to evaluate and compare the flexural strength of commercially available acrylic (trevalone) and modified polymethylmethacrylate (PMMA). MATERIALS AND METHODS: Four groups were tested; Group 1- control group regular MMA, group 2-2% methacrylic acid, 88% MMA, group 3-16% methacrylic acid, 84% MMA group 4- 20% methacrylic acid, 80% MMA 15 resin specimens of each group were polymerized. After processing, the specimens were subjected for flexural strength testing using three point bending test in a Universal Testing Machine. All data was statistically analyzed with one-way ANOVA, differences within the groups were analyzed by Scheffe's analysis. RESULTS: As the ratio of incorporated methacrylic acid to PMMA increased, the flexural strength decreased. Analysis of data revealed a significant decrease in flexural strength of specimens (p < 0.000) after incorporation of 12%, 16%, 20% methacrylic acid to heat polymerized acrylic resin, when compared with the control group. Lowest flexural strength was observed with specimens containing 20% methacrylic acid and highest flexural strength was observed with specimens containing conventional monomer without methacrylic acid. CONCLUSION: It was observed that as the concentration of methacrylic acid in heat polymerized acrylic resin increases, the flexural strength decreases. Lowest flexural strength was observed with specimens containing 20% methacrylic acid and highest flexural strength was observed with specimens containing conventional monomer without methacrylic acid. CLINICAL SIGNIFICANCE: The major advantages of addition of methacrylic acid to polymethylmethacrylate could be for the elderly people with restricted manual dexterity or cognitive disturbances, especially for patients who do not follow an adequate denture cleansing protocol and diabetic patients who are more susceptible for denture stomatitis.