التفاصيل البيبلوغرافية
| العنوان: |
De novo designing, assessment of target affinity and binding interactions against aromatase: Discovery of novel leads as anti-breast cancer agents. |
| المؤلفون: |
Verma, Sant Kumar, Ratre, Pooja, Jain, Akhlesh Kumar, Liang, Chengyuan, Gupta, Ghanshyam Das, Thareja, Suresh |
| المصدر: |
Structural Chemistry; Apr2021, Vol. 32 Issue 2, p847-858, 12p |
| مصطلحات موضوعية: |
HORMONE receptor positive breast cancer, AROMATASE, AROMATASE inhibitors, INTERNET servers |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
|
Copyright of Structural Chemistry is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
