PMID- 22530909
OWN - NLM
STAT- MEDLINE
DCOM- 20121218
LR  - 20191027
IS  - 1875-6638 (Electronic)
IS  - 1573-4064 (Linking)
VI  - 8
IP  - 4
DP  - 2012 Jul
TI  - A QSAR analysis of 2-phenoxy-N-substituted acetamide analogues as 
      hypoxia-inducible factor-1(HIF-1) inhibitors: a rational approach to anticancer 
      drug design.
PG  - 599-614
AB  - A set of thirty one substituted 2-phenoxy-N-phenylacetamide derivatives with 
      HIF-1 inhibitory activities was subjected to 2D and 3D Quantitative Structure 
      Activity Relationship (QSAR) studies using various combinations of descriptors. 
      2D-QSAR was performed using Multiple Linear Regression (MLR), Principal Component 
      Regression (PCR) and Partial Least Squares Regression (PLS) methods. Among these 
      three methods Multiple Linear Regression (MLR) led to the statistically 
      significant best 2D-QSAR Model-I having correlation coefficient r(2) = 0.9469 and 
      cross validated squared correlation coefficient q(2) = 0.8933 with external 
      predictive ability of pred_r(2) = 0.7128 with the descriptors like SssNHE-index, 
      slogp, T_O_N_1 and T_2_Cl_1. 3D-QSAR study was performed using the simulated 
      annealing variable selection procedures k-nearest neighbor molecular field 
      analysis approach. 3D-QSAR shows interesting results in terms of internal and 
      external predictability. Molecular field analysis was applied for the generation 
      of steric, hydrophobic and electrostatic descriptors based on aligned structures 
      which shows good correlative and predictive capabilities in terms of q(2) = 
      0.9672 and pred_r(2) = 0.8480. Hence the model proposed in this work provides 
      important structural insight in designing novel derivatives with specific HIF-1 
      inhibitory activity.
FAU - Noolvi, Malleshappa N
AU  - Noolvi MN
AD  - Department of Pharmaceutical Chemistry, Shree Dhanvantary Pharmacy College, Kim 
      (Surat)-394110, Gujrat, India. mnoolvi@yahoo.co.uk
FAU - Patel, Harun M
AU  - Patel HM
FAU - Kamboj, Sarita
AU  - Kamboj S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Med Chem
JT  - Medicinal chemistry (Shariqah (United Arab Emirates))
JID - 101240303
RN  - 0 (Acetamides)
RN  - 0 (Acetanilides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 8XOE1JSO29 (acetamide)
SB  - IM
MH  - Acetamides/*chemistry/*pharmacology
MH  - Acetanilides/*chemistry/pharmacology
MH  - Antineoplastic Agents/*chemistry/*pharmacology
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - *Drug Design
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors
MH  - Inhibitory Concentration 50
MH  - Linear Models
MH  - Models, Molecular
MH  - Protein Binding/drug effects
MH  - *Quantitative Structure-Activity Relationship
EDAT- 2012/04/26 06:00
MHDA- 2012/12/19 06:00
CRDT- 2012/04/26 06:00
PHST- 2011/06/07 00:00 [received]
PHST- 2011/11/21 00:00 [revised]
PHST- 2012/02/11 00:00 [accepted]
PHST- 2012/04/26 06:00 [entrez]
PHST- 2012/04/26 06:00 [pubmed]
PHST- 2012/12/19 06:00 [medline]
AID - MC-EPUB-20120424-003 [pii]
AID - 10.2174/157340612801216274 [doi]
PST - ppublish
SO  - Med Chem. 2012 Jul;8(4):599-614. doi: 10.2174/157340612801216274.