De novo designing, assessment of target affinity and binding interactions against aromatase: Discovery of novel leads as anti-breast cancer agents
| dc.contributor.author | Verma, Sant Kumar | |
| dc.contributor.author | Ratre, Pooja | |
| dc.contributor.author | Jain, Akhlesh Kumar | |
| dc.contributor.author | Liang, Chengyuan | |
| dc.contributor.author | Gupta, Ghanshyam Das | |
| dc.contributor.author | Thareja, Suresh | |
| dc.date.accessioned | 2024-01-21T10:38:14Z | |
| dc.date.accessioned | 2024-08-13T12:05:08Z | |
| dc.date.available | 2024-01-21T10:38:14Z | |
| dc.date.available | 2024-08-13T12:05:08Z | |
| dc.date.issued | 2020-11-13T00:00:00 | |
| dc.description.abstract | Aromatase inhibitors (AIs) have been emerged as promising anti-cancer agents for the treatment of hormone dependent breast cancer (HDBC) in women because of their excellent ability of inhibiting oestrogen synthesis. Here, we have implicated structure-based comprehensive approaches to discover novel drug/lead-like AIs. The molecular modelling and energy optimization were performed using Chem Office package. The e-LEA3D web server was used to design novel drug/lead-like AIs as well as generation of ADME/drug-likeness parameters. Target binding affinities and mode of binding interactions were mapped using Molegro Virtual Docker (MVD) to re-optimize the best de novo generated molecules. We have successfully designed novel AIs (compounds 1�7) using de novo technique performed on e-LEA3D. All the designed molecules were found optimum drug-like candidates based on various in silico screening parameters including �rule of five�. The energy optimized conformers of generated molecules (1�7) were docked in the active site, corresponding to co-crystallized androstenedione (ASD), of aromatase to predict ligand-target binding affinity and their binding interactions. The molecules (1�7) showed comparable to higher binding affinity towards aromatase with MolDock Score ranges from ? 134.881 to ? 152.453�Kcal/mol as compared with natural substrate ASD (? 128.639�Kcal/mol) and standard letrozole (? 136.784�Kcal/mol). The de novo designed molecules (1�7) can be developed as novel AIs, and their binding properties can be used for the further designing of newer AIs by medicinal chemists. � 2020, Springer Science+Business Media, LLC, part of Springer Nature. | en_US |
| dc.identifier.doi | 10.1007/s11224-020-01673-y | |
| dc.identifier.issn | 10400400 | |
| dc.identifier.uri | http://10.2.3.109/handle/32116/3500 | |
| dc.identifier.url | http://link.springer.com/10.1007/s11224-020-01673-y | |
| dc.language.iso | en_US | en_US |
| dc.publisher | Springer | en_US |
| dc.subject | Anti-cancer agents | en_US |
| dc.subject | Aromatase inhibitors | en_US |
| dc.subject | Breast cancer | en_US |
| dc.subject | De novo designing | en_US |
| dc.subject | e-LEA3D | en_US |
| dc.subject | Molecular docking | en_US |
| dc.title | De novo designing, assessment of target affinity and binding interactions against aromatase: Discovery of novel leads as anti-breast cancer agents | en_US |
| dc.title.journal | Structural Chemistry | en_US |
| dc.type | Article | en_US |
| dc.type.accesstype | Closed Access | en_US |