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Title |
Molecular designing and in silico evaluation of darunavir derivatives as anticancer agents
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Authors |
Manoj kumar Mahto1, 2, Nanda Kumar Yellapu3, Ravendra Babu Kilaru4, Naga Raju Chamarthi4 & Matcha Bhaskar2* |
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Affiliation |
1Department of Biotechnology, Acharya Nagarjuna University, Guntur, AP, India, 522510; 2Division of Animal Biotechnology, Department of Zoology, Sri Venkateswara University, Tirupati, AP, India, 517502; 3Biomedical Informatics Center, Vector Control Research Center, Indian Council of Medical Research, Pondicherry, India, 605006; 4Department of Chemistry, Sri Venkateswara University, Tirupati, AP, 517502, India
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matchabhaskar2010@gmail.com; *Corresponding author
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Article Type |
Hypothesis |
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Date |
Received April 11, 2014; Accepted April 17, 2014; Published April 23, 2014
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Abstract |
Darunavir is a synthetic nonpeptidic protease inhibitor which has been tested for anticancer properties. To deduce and enhance the anticancer activity of the Darunavir, we have modified its reactive moiety in an effective way. We designed 9 analogues in ChemBioOffice 2010 and minimized using the LigPrep tool of Schrödinger 2011. These analogues can obstruct the activity of other signalling pathways which are implicated in many tumors. Results of the QikProp showed that all the analogues lied in the specified range of all the pharmacokinetic (ADMET) properties required to become the successful drug. Docking study was performed to test its anticancer activity against the biomarkers of the five main types of cancers i.e. bone, brain, breast, colon and skin cancer. Grid was generated for each oncoproteins by specifying the active site amino acids. The binding model of best scoring analogue with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. An analysis of the receptor-ligand interaction studies revealed that these nine Darunavir analogues are active against all cancer biomarkers and have the features to prove themselves as anticancer drugs, further to be synthesized and tested against the cell lines.
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Keywords |
Darunavir, Cancer, EGFR, VEGFR2, Docking, HIV, ADMET
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Citation |
Mahto et al.
Bioinformation 10(4): 221-226 (2014) |
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. |