Abstract
BackgroundPyrimidine is an important pharmacophore in the field of medicinal chemistry and exhibit a broad spectrum of biological potentials. A study was carried out to identify the target protein of potent bis-pyrimidine derivatives using reverse docking program. PharmMapper, a robust online tool was used for identifying the target proteins based on reverse pharmacophore mapping. The murine macrophage (RAW 264.7) and human embryonic kidney (HEK-293) cancer cell line used for selectivity and safety study.MethodsAn 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 discussionThe 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.ConclusionFrom 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.
Highlights
Pyrimidine is an important pharmacophore in the field of medicinal chemistry and exhibit a broad spectrum of biological potentials
Data set The data set of bis-pyrimidine derivatives (1–20), which exhibited selective antiproliferative activity against human colorectal carcinoma cancer cell line (HCT116) (IC50 = ranging from 0.73 to 4.16 μmol/mL) but not showed significant results against murine macrophage cell line (RAW 264.7) (IC50 = ranging from 3.50 to 4.16 μmol/mL) (Table 1) were selected from the literature for development of the pharmacophore model
Target identification of compounds An open web server PharmMapper was used to identify the possible target of the developed compounds through reverse pharmacophore mapping [6]
Summary
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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
