Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Virtual screening, identification and experimental testing of novel inhibitors of PBEF1/Visfatin/ NMPRTase for glioma therapy. | Chandra et al. Journal of Clinical Bioinformatics 2011 1 5 http content 1 1 5 JOURNAL OF CLINICAL BIOINFORMATICS RESEARCH Open Access Virtual screening identification and experimental testing of novel inhibitors of PBEF1 Visfatin NMPRTase for glioma therapy 1 11 2 2 Nagasuma Chandra Raghu Bhagavat Eshita Sharma P Sreekanthreddy Kumaravel Somasundaram Abstract Background Pre-B-cell colony enhancing factor 1 gene PBEF1 encodes nicotinamide phosphoribosyltransferase NMPRTase which catalyses the rate limiting step in the salvage pathway of NAD metabolism in mammalian cells. PBEF1 transcript and protein levels have been shown to be elevated in glioblastoma and a chemical inhibitor of NMPRTase has been shown to specifically inhibit cancer cells. Methods Virtual screening using docking was used to screen a library of more than 13 000 chemical compounds. A shortlisted set of compounds were tested for their inhibition activity in vitro by an NMPRTase enzyme assay. Further the ability of the compounds to inhibit glioma cell proliferation was carried out. Results Virtual screening resulted in short listing of 34 possible ligands of which six were tested experimentally using the NMPRTase enzyme inhibition assay and further with the glioma cell viability assays. Of these two compounds were found to be significantly efficacious in inhibiting the conversion of nicotinamide to NAD and out of which one compound 3-amino-2-benzyl-7-nitro-4- 2-quinolyl- -1 2-dihydroisoquinolin-1-one was found to inhibit the growth of a PBEF1 over expressing glioma derived cell line U87 as well. Conclusions Thus a novel inhibitor has been identified through a structure based drug discovery approach and is further supported by experimental evidence. Background Gliomas are primary malignant tumors originating in the brain and account for 80 of adult primary brain tumors. The prognosis for patients with glioblastoma multiforme a virulent variety of the disease is rather poor .
