Integrating regression and classification-based QSARs with molecular docking analyses to explore the structure-antiaromatase activity relationships of letrozole-based analogs
Aromatase is a multienzyme complex responsible for the biosynthesis of estrogen and its level has been found higher in breast cancer. Although the designing strategy of aromatase inhibitors (AIs) has continued for more than four decades, it may still be in demand to design highly effective and less toxic AIs. In this study, several chemometric approaches have been used to explore the important structural features of a series of letrozole-based analogs for their promising aromatase inhibitory activity. All techniques are statistically validated individually and in turn, validated with each other along with the structure–activity relationship (SAR) observations. The imidazole ring has been found to interact with the heme iron, whereas the triazole ring system has not shown any interaction. Moreover, imidazole function is better than 1,2,3-triazole, whereas 1,2,3-triazole is better than the 1,2,5-triazole ring system. Additionally, a bulky aryl substitution in the azole ring along with the orientation of the azole nitrogens and the cyanophenyl function has an essential role in the inhibition of aromatase. Furthermore, a cyano group substituted at the phenyl moiety interacts with Arg115, Met374, and Ser478 at the enzyme active site to form hydrogen bonding interactions. These observations are useful for designing potential AIs in the future..
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:95 |
|---|---|
| Enthalten in: |
Canadian journal of chemistry - 95(2017), 12, Seite 1285-1295 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gayen, Shovanlal [VerfasserIn] |
|---|
| Links: |
|---|
| RVK: |
|---|
| doi: |
10.1139/cjc-2017-0419 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC1999105591 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | OLC1999105591 | ||
| 003 | DE-627 | ||
| 005 | 20230715083556.0 | ||
| 007 | tu | ||
| 008 | 171228s2017 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1139/cjc-2017-0419 |2 doi | |
| 028 | 5 | 2 | |a PQ20171228 |
| 035 | |a (DE-627)OLC1999105591 | ||
| 035 | |a (DE-599)GBVOLC1999105591 | ||
| 035 | |a (PRQ)g1308-971e38c9ac78db30f72a5825894740392fa1b7f9217ec7380a6d5bda31675d390 | ||
| 035 | |a (KEY)0073021120170000095001201285integratingregressionandclassificationbasedqsarswi | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 540 |q DE-600 |
| 084 | |a VA 2870 |q AVZ |2 rvk | ||
| 084 | |a 35.00 |2 bkl | ||
| 100 | 1 | |a Gayen, Shovanlal |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Integrating regression and classification-based QSARs with molecular docking analyses to explore the structure-antiaromatase activity relationships of letrozole-based analogs |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 520 | |a Aromatase is a multienzyme complex responsible for the biosynthesis of estrogen and its level has been found higher in breast cancer. Although the designing strategy of aromatase inhibitors (AIs) has continued for more than four decades, it may still be in demand to design highly effective and less toxic AIs. In this study, several chemometric approaches have been used to explore the important structural features of a series of letrozole-based analogs for their promising aromatase inhibitory activity. All techniques are statistically validated individually and in turn, validated with each other along with the structure–activity relationship (SAR) observations. The imidazole ring has been found to interact with the heme iron, whereas the triazole ring system has not shown any interaction. Moreover, imidazole function is better than 1,2,3-triazole, whereas 1,2,3-triazole is better than the 1,2,5-triazole ring system. Additionally, a bulky aryl substitution in the azole ring along with the orientation of the azole nitrogens and the cyanophenyl function has an essential role in the inhibition of aromatase. Furthermore, a cyano group substituted at the phenyl moiety interacts with Arg115, Met374, and Ser478 at the enzyme active site to form hydrogen bonding interactions. These observations are useful for designing potential AIs in the future. | ||
| 650 | 4 | |a amarrage moléculaire | |
| 650 | 4 | |a 2D-QSAR | |
| 650 | 4 | |a inhibiteurs de l’aromatase à base de létrozole | |
| 650 | 4 | |a letrozole-based aromatase inhibitors | |
| 650 | 4 | |a HQSAR | |
| 650 | 4 | |a QSAR-3D CoMFA | |
| 650 | 4 | |a 3D-QSAR comparative molecular field analysis (CoMFA) | |
| 650 | 4 | |a QSAR-2D | |
| 650 | 4 | |a molecular docking | |
| 650 | 4 | |a hologram QSAR (HQSAR) | |
| 650 | 4 | |a Open3DQSAR | |
| 650 | 4 | |a Nitriles | |
| 650 | 4 | |a Antimitotic agents | |
| 650 | 4 | |a Heme | |
| 650 | 4 | |a Estrogen | |
| 650 | 4 | |a Analysis | |
| 650 | 4 | |a Physiological aspects | |
| 650 | 4 | |a Enzymes | |
| 650 | 4 | |a Hydrogen | |
| 650 | 4 | |a Antineoplastic agents | |
| 650 | 4 | |a Triazoles | |
| 700 | 1 | |a Adhikari, Nilanjan |4 oth | |
| 700 | 1 | |a Jha, Tarun |4 oth | |
| 700 | 1 | |a Amin, Sk. Abdul |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Canadian journal of chemistry |d Ottawa, Ont. : Council, 1951 |g 95(2017), 12, Seite 1285-1295 |w (DE-627)129078034 |w (DE-600)2988-9 |w (DE-576)014410583 |x 0008-4042 |7 nnns |
| 773 | 1 | 8 | |g volume:95 |g year:2017 |g number:12 |g pages:1285-1295 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1139/cjc-2017-0419 |3 Volltext |
| 856 | 4 | 2 | |u http://www.nrcresearchpress.com/doi/abs/10.1139/cjc-2017-0419 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a SSG-OLC-CHE | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_59 | ||
| 912 | |a GBV_ILN_70 | ||
| 912 | |a GBV_ILN_2006 | ||
| 912 | |a GBV_ILN_2015 | ||
| 912 | |a GBV_ILN_4125 | ||
| 936 | r | v | |a VA 2870 |
| 936 | b | k | |a 35.00 |q AVZ |
| 951 | |a AR | ||
| 952 | |d 95 |j 2017 |e 12 |h 1285-1295 | ||