Combating breast cancer with non-steroidal aromatase inhibitors (NSAIs) : Understanding the chemico-biological interactions through comparative SAR/QSAR study
Copyright © 2017 Elsevier Masson SAS. All rights reserved..
It is a challenging task to design target-specific and less toxic non-steroidal aromatase inhibitors (NSAIs) though the modeling studies for designing anti-aromatase molecules have been continuing for more than two decades to fight the dreaded estrogen-dependent breast cancer. In this article, different validated QSAR models are developed and analyzed to understand important physicochemical and structural parameters modulating the aromatase inhibitory activity of NSAIs. Physicochemical properties such as molar refractivity and dipole moment are found to be the most important parameters for controlling aromatase inhibition. This indicates the characteristic of bulky, complex and steric properties as well as, the flexibility of molecules is playing pivotal roles for aromatase inhibition. In many cases, hydrophobicity also plays important contribution. Regarding the structural point of view, some important indicator parameters are also found to be important for aromatase inhibitory activity. Though azole function is playing a crucial role by coordinating the heme moiety of the aromatase enzyme, the imidazole or the imidazolylmethyl ring systems may be better NSAIs than triazole, tetrazole or other azoles. The 4-pyridylmethyl group containing compounds are also found to be better NSAIs. The QSAR study, in a nutshell, provides a detailed understanding of the effectivity of NSAIs which is dependent mainly on the shape and size as well as the steric features of molecules and the heme-coordinator azole functions. These findings may open up a new horizon for designing new potential NSAIs that can be effective to reduce the mortality rate of breast cancer in future.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:137 |
|---|---|
| Enthalten in: |
European journal of medicinal chemistry - 137(2017) vom: 08. Sept., Seite 365-438 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Adhikari, Nilanjan [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 20.09.2017 Date Revised 20.09.2017 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.ejmech.2017.05.041 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM273009915 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM273009915 | ||
| 003 | DE-627 | ||
| 005 | 20231225000135.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejmech.2017.05.041 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0910.xml |
| 035 | |a (DE-627)NLM273009915 | ||
| 035 | |a (NLM)28622580 | ||
| 035 | |a (PII)S0223-5234(17)30402-6 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Adhikari, Nilanjan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Combating breast cancer with non-steroidal aromatase inhibitors (NSAIs) |b Understanding the chemico-biological interactions through comparative SAR/QSAR study |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.09.2017 | ||
| 500 | |a Date Revised 20.09.2017 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a It is a challenging task to design target-specific and less toxic non-steroidal aromatase inhibitors (NSAIs) though the modeling studies for designing anti-aromatase molecules have been continuing for more than two decades to fight the dreaded estrogen-dependent breast cancer. In this article, different validated QSAR models are developed and analyzed to understand important physicochemical and structural parameters modulating the aromatase inhibitory activity of NSAIs. Physicochemical properties such as molar refractivity and dipole moment are found to be the most important parameters for controlling aromatase inhibition. This indicates the characteristic of bulky, complex and steric properties as well as, the flexibility of molecules is playing pivotal roles for aromatase inhibition. In many cases, hydrophobicity also plays important contribution. Regarding the structural point of view, some important indicator parameters are also found to be important for aromatase inhibitory activity. Though azole function is playing a crucial role by coordinating the heme moiety of the aromatase enzyme, the imidazole or the imidazolylmethyl ring systems may be better NSAIs than triazole, tetrazole or other azoles. The 4-pyridylmethyl group containing compounds are also found to be better NSAIs. The QSAR study, in a nutshell, provides a detailed understanding of the effectivity of NSAIs which is dependent mainly on the shape and size as well as the steric features of molecules and the heme-coordinator azole functions. These findings may open up a new horizon for designing new potential NSAIs that can be effective to reduce the mortality rate of breast cancer in future | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a ) | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a Non steroidal aromatase inhibitors (NSAIs | |
| 650 | 4 | |a Quantitative structure-activity relationships (QSARs) | |
| 650 | 4 | |a Structure-activity relationships (SARs) | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Aromatase Inhibitors |2 NLM | |
| 650 | 7 | |a Aromatase |2 NLM | |
| 650 | 7 | |a EC 1.14.14.1 |2 NLM | |
| 700 | 1 | |a Amin, Sk Abdul |e verfasserin |4 aut | |
| 700 | 1 | |a Saha, Achintya |e verfasserin |4 aut | |
| 700 | 1 | |a Jha, Tarun |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of medicinal chemistry |d 1994 |g 137(2017) vom: 08. Sept., Seite 365-438 |w (DE-627)NLM106608835 |x 1768-3254 |7 nnns |
| 773 | 1 | 8 | |g volume:137 |g year:2017 |g day:08 |g month:09 |g pages:365-438 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejmech.2017.05.041 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 137 |j 2017 |b 08 |c 09 |h 365-438 | ||