Biotechnology and Bioinformatics - Publications

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Browsing Biotechnology and Bioinformatics - Publications by Subject "3D-QSAR"
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    Development of pyridine dicoumarols as potent anti HIV-1 leads, targeting HIV-1 associated topoisomeraseIIβ kinase
    ( 2017-09-01) Kammari, Kurumurthy ; Devaraya, Kiran ; Bommakanti, Akhila ; Kondapi, Anand K.
    Aim: A structural study of a series of pyridine dicoumarol derivatives with potential activity against a novel Topoisomerase IIβ kinase which was identified in the HIV-1 viral lysate, compounds were designed and synthesized based on a 3D-QSAR study. Materials & methods: Based on QSAR model we have designed and synthesized a series of pyridine dicoumarol derivatives and characterized by spectral studies, all the molecules are biologically evaluated by kinase assay, cytotoxicity assay, ELISA and PCR method. Result: We demonstrated the achievement of water soluble disodium pyridine dicoumarate derivatives showing high anti-HIV-1 activity (IC50 < 25 nM) which provides a crucial point for further development of pyridine dicoumarol series as HIV-1-associated topoisomerase IIβ kinase inhibitors for clinical application against AIDS. Conclusion: A new class of anti-HIV-1 lead compounds have been designed and tested. Further studies would result in development of novel and potential drugs.
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    In silico screening for identification of novel β-1,3-glucan synthase inhibitors using pharmacophore and 3D-QSAR methodologies
    ( 2016-12-01) Meetei, Potshangbam Angamba ; Rathore, R. S. ; Prabhu, N. Prakash ; Vindal, Vaibhav
    The enzyme β-1,3-glucan synthase, which catalyzes the synthesis of β-1,3-glucan, an essential and unique structural component of the fungal cell wall, has been considered as a promising target for the development of less toxic anti-fungal agents. In this study, a robust pharmacophore model was developed and structure activity relationship analysis of 42 pyridazinone derivatives as β-1,3-glucan synthase inhibitors were carried out. A five-point pharmacophore model, consisting of two aromatic rings (R) and three hydrogen bond acceptors (A) was generated. Pharmacophore based 3D-QSAR model was developed for the same reported data sets. The generated 3D-QSAR model yielded a significant correlation coefficient value (R2 = 0.954) along with good predictive power confirmed by the high value of cross-validated correlation coefficient (Q2 = 0.827). Further, the pharmacophore model was employed as a 3D search query to screen small molecules database retrieved from ZINC to select new scaffolds. Finally, ADME studies revealed the pharmacokinetic efficiency of these compounds.
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    In silico screening for identification of novel β-1,3-glucan synthase inhibitors using pharmacophore and 3D-QSAR methodologies
    ( 2016-12-01) Meetei, Potshangbam Angamba ; Rathore, R. S. ; Prabhu, N. Prakash ; Vindal, Vaibhav
    The enzyme β-1,3-glucan synthase, which catalyzes the synthesis of β-1,3-glucan, an essential and unique structural component of the fungal cell wall, has been considered as a promising target for the development of less toxic anti-fungal agents. In this study, a robust pharmacophore model was developed and structure activity relationship analysis of 42 pyridazinone derivatives as β-1,3-glucan synthase inhibitors were carried out. A five-point pharmacophore model, consisting of two aromatic rings (R) and three hydrogen bond acceptors (A) was generated. Pharmacophore based 3D-QSAR model was developed for the same reported data sets. The generated 3D-QSAR model yielded a significant correlation coefficient value (R2 = 0.954) along with good predictive power confirmed by the high value of cross-validated correlation coefficient (Q2 = 0.827). Further, the pharmacophore model was employed as a 3D search query to screen small molecules database retrieved from ZINC to select new scaffolds. Finally, ADME studies revealed the pharmacokinetic efficiency of these compounds.
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    Investigations and design of pyridine-2-carboxylic acid thiazol-2-ylamide analogs as methionine aminopeptidase inhibitors using 3D-QSAR and molecular docking
    ( 2014-01-01) Meetei, Potshangbam Angamba ; Hauser, Alexander S. ; Raju, Prathigadapa S. ; Rathore, R. S. ; Prabhu, N. Prakash ; Vindal, Vaibhav
    Methionine amino peptidases (MetAPs) are metalloproteases that remove co-translational N-terminal methionine from nascent polypeptide chains. Due to their essential role in protein synthesis, MetAPs are considered as potential targets for antibacterial drugs. In the present work, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on a series of pyridine-2-carboxylic acid thiazol-2-ylamidebased MetAP inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The models were developed using 30 training set molecules. The optimum CoMFA and CoMSIA models obtained for the training set were statistically significant with cross-validated correlation coefficients (q2) of 0.799 and 0.704 and conventional correlation coefficients (r2) of 0.989 and 0.954, respectively. These inhibitors were docked into MetAP active site. The CoMFA and CoMSIA field contour maps correlate well with the structural characteristics of the binding pocket of MetAP active site. Using the knowledge of structure-activity relationship and receptor-ligand interactions from 3D-QSAR model and the docked complexes, four new pyridine-2-carboxylic acid thiazol-2-ylamide analogs were designed. These analogs exhibit significantly better predicted activity than the reported molecules. The present work has implications for the development of novel antibiotics as potent MetAP inhibitors. © Springer Science+Business Media 2014.
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    Investigations and design of pyridine-2-carboxylic acid thiazol-2-ylamide analogs as methionine aminopeptidase inhibitors using 3D-QSAR and molecular docking
    ( 2014-01-01) Meetei, Potshangbam Angamba ; Hauser, Alexander S. ; Raju, Prathigadapa S. ; Rathore, R. S. ; Prabhu, N. Prakash ; Vindal, Vaibhav
    Methionine amino peptidases (MetAPs) are metalloproteases that remove co-translational N-terminal methionine from nascent polypeptide chains. Due to their essential role in protein synthesis, MetAPs are considered as potential targets for antibacterial drugs. In the present work, three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on a series of pyridine-2-carboxylic acid thiazol-2-ylamidebased MetAP inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. The models were developed using 30 training set molecules. The optimum CoMFA and CoMSIA models obtained for the training set were statistically significant with cross-validated correlation coefficients (q2) of 0.799 and 0.704 and conventional correlation coefficients (r2) of 0.989 and 0.954, respectively. These inhibitors were docked into MetAP active site. The CoMFA and CoMSIA field contour maps correlate well with the structural characteristics of the binding pocket of MetAP active site. Using the knowledge of structure-activity relationship and receptor-ligand interactions from 3D-QSAR model and the docked complexes, four new pyridine-2-carboxylic acid thiazol-2-ylamide analogs were designed. These analogs exhibit significantly better predicted activity than the reported molecules. The present work has implications for the development of novel antibiotics as potent MetAP inhibitors. © Springer Science+Business Media 2014.