Materials and Methods: This cross-sectional study was conducted among the GDPs of Karachi. A questionnaire was designed to collect data from 100 GDPs. The questionnaire included general/demographic information (practitioner's education, experience, and place of practice) and an average number of fixed prosthesis constructed by the GDP. The questionnaire was further categorized to evaluate the knowledge/practice of pontic design selection and latest recommendations.
Results: For the maxillary anterior segment, the ridge lap pontic was the most common (32%) followed by the modified ridge lap (28%). In the maxillary posterior segment, the ridge lap pontic was the most common (37%) followed by sanitary design (34%). For the mandibular anterior segment, the modified ridge lap (50%) was the most common followed by ridge lap pontic (17%). In case of the mandibular posterior segment, the sanitary design (34%) was the most common followed by ridge lap pontic (30%).
Conclusions: The pontic design selection for the fixed prosthesis is a neglected domain. The contemporary guidelines are not followed with full spirit by the GDPs leading to wide variations in the pontic design selection.
METHODS: An open web server PharmMapper was used to identify the possible target of the developed compounds through reverse pharmacophore mapping. The results were analyzed and validated through docking with Schrodinger v9.6 using 10 protein GTPase HRas selected as possible target. The docking studies with Schrödinger validated the binding behavior of bis-pyrimidine compounds within GTP binding pocket. MTT and sulforhodamine assay were used as antiproliferative activity.
RESULTS AND DISCUSSION: The protein was found one of the top scored targets of the compound 18, hence, the GTPase HRas protein was found crucial to be targeted for competing cancer. Toxicity study demonstrated the significant selectivity of most active compounds, 12, 16 and 18 showed negligible cell toxicity at their IC50 concentration.
CONCLUSION: From the results, we may conclude that GTPase HRas as a possible target of studied bis-pyrimidine derivatives where the retrieved information may be quite useful for rational drug designing.