Structure Based Drug Designing of Histone Deacetylase-2 inhibitors as an Anticancer Agents (Record no. 19297)
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| control field | OSt |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20230504131108.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 230504b xxu||||| |||| 00| 0 eng d |
| 040 ## - CATALOGING SOURCE | |
| Original cataloging agency | AIKTC-KRRC |
| Transcribing agency | AIKTC-KRRC |
| 100 ## - MAIN ENTRY--PERSONAL NAME | |
| 9 (RLIN) | 20670 |
| Author | Bisht, Somya |
| 245 ## - TITLE STATEMENT | |
| Title | Structure Based Drug Designing of Histone Deacetylase-2 inhibitors as an Anticancer Agents |
| 250 ## - EDITION STATEMENT | |
| Volume, Issue number | Vol.61(9), Sep |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
| Place of publication, distribution, etc. | New Delhi |
| Name of publisher, distributor, etc. | CSIR |
| Year | 2022 |
| 300 ## - PHYSICAL DESCRIPTION | |
| Pagination | 976-988p. |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | Background and purpose- Histone deacetylase 2 (HDAC2) in tumour development and carcinogenesis as a promising therapeutic target for cancer treatment. HDAC-2 belongs to class I histone deacetylase and acts as a transcriptional repressor through the deacetylation of lysine residues present at the N-terminal tail of histone proteins (H2A, H2B, H3 and H4). They are overexpressed in various solid tumours like cutaneous t cell lymphoma, colorectal, prostate cancer, lung cancer, breast cancer, gastric cancer, liver cancer and medulloblastoma. Hence, targeting HDAC-2 could be rewarding strategy to combat cancer. The goal of the research is to design, develop and identification of molecules through docking, Ligplot, ADMET properties and dynamic studies. Objective- To update HDAC-2 databases as a resource for Structure based drug designing. Validation of model by understanding the interaction pattern with known inhibitors. To identify selective and trapping HDAC-2 inhibitors by targeting the catalytic domain through structure-based pharmacophore study. To design novel HDAC inhibitors (HDACi) analogues for further generation of new compounds through software. Molecular dynamics simulations for most active compound. Methods- In the present study HDAC-2 protein (PDB-4LY1) from RCSB PDB screened and retrieved. The different set of data for ligand preparation were downloaded from CHEMBL, NCI, Anticancer databases and FDA approved drugs of HDACi were downloaded from PubChem. The compounds were screened with two software Schrodinger and gold. The multiset framework combining ligand preparation, protein preparation, grid generation, ADMET prediction, molecular docking, Ligplot analysis and molecular dynamics (MD) simulation studies was performed to find the potential compound with HDAC-2 binding affinity. Result- The optimised compound shows high docking score from ChEMBL (-14.078) and NCI library it shows (-12.083) as compared to reference drug Panobinostat (-9.157). binding energy, hydrogen bonding and hydrophobic interaction against the reference compound. 20 compounds were selected as the best HDAC2 inhibitors based on the glide score, binding energy, hydrogen bonding, hydrophobic interaction. Top two compound show Ligplot analysis. Then the one highest docked compound shows dynamic study at 50ns shows binding stability with the inhibitor. Finally find its ADMET property. Conclusion- The virtual screening of drugs through software is ongoing process and 20 modified analogues those which satisfied all the screening results have been found to be better than the conventional drugs available. Further, synthesis, in vivo and cytotoxic studies of synthesised molecules are under process. KEYWORDS- Histone acetylase, histone deacetylase, histone deacetylase-2, molecular dynamics, 4LY1, ADME property, histone deacetylase inhibitor, Optimized Potential for Liquid Simulation 3e, high throughput virtual screening, standard precision, extra precision. |
| 650 #0 - SUBJECT ADDED ENTRY--TOPICAL TERM | |
| 9 (RLIN) | 5009 |
| Topical term or geographic name entry element | GENERAL CHEMISTRY |
| 700 ## - ADDED ENTRY--PERSONAL NAME | |
| 9 (RLIN) | 20671 |
| Co-Author | Subbarao, Dr. Naidu |
| 773 0# - HOST ITEM ENTRY | |
| Title | Indian journal of chemistry (Section B) |
| Place, publisher, and date of publication | New Delhi NISCAIR-CSIR 2005 |
| International Standard Serial Number | 0019-5103 |
| 856 ## - ELECTRONIC LOCATION AND ACCESS | |
| URL | http://op.niscpr.res.in/index.php/IJC/article/view/60668 |
| Link text | Click here |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | |
| Koha item type | Articles Abstract Database |
| Withdrawn status | Lost status | Source of classification or shelving scheme | Damaged status | Not for loan | Permanent Location | Current Location | Shelving location | Date acquired | Barcode | Date last seen | Price effective from | Koha item type |
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| School of Pharmacy | School of Pharmacy | Archieval Section | 2023-05-04 | 2023-0804 | 2023-05-04 | 2023-05-04 | Articles Abstract Database |