Identification of novel NAD(P)H dehydrogenase [quinone] 1 antagonist using computational approaches

Journal of Biomolecular Structure & Dynamics
Rajendran SelvakumarKrishnasamy Gunasekaran

Abstract

NAD(P)H: quinone oxidoreductase 1 (NQO1) inhibitors are proved as promising therapeutic agents against cancer. This study is to determine potent NAD(P)H-dependent NQO1 inhibitors with new scaffold. Pharmacophore-based three-dimensional (3D) QSAR model has been built based on 45 NQO1 inhibitors reported in the literature. The structure-function correlation coefficient graph represents the relationship between phase activity and phase predicted activity for training and test sets. A QSAR model statistics shows the excellent correlation of the generated model. Pharmacophore hypothesis (AARR) yielded a statistically significant 3D QSASR model with a correlation coefficient of r2 = 0.99 as well as an excellent predictive power. From the analysis of pharmacophore-based virtual screening using by SPEC database, 4093 hits were obtained and were further filtered using virtual screening filters (HTVS, SP, XP) through structure based molecular docking. Based on glide energy and docking score, seven lead compounds show better binding affinity compared to the co-crystal inhibitor. The results of induced fit docking and prime/MM-GBSA suggest that leads AN-153/J117103 and AT-138/KB09997 binding with the catalytic site. Further, to understandi...Continue Reading

References

Mar 15, 1990·International Journal of Cancer. Journal International Du Cancer·J J Schlager, G Powis
Aug 1, 1995·Free Radical Biology & Medicine·I KoharP T Southwell-Keely
Dec 11, 1999·Journal of Toxicology and Environmental Health. Part a·P LinC Y Chen
Oct 27, 2001·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·S J LewisA C Povey
May 23, 2002·International Journal of Clinical Oncology·Nobuyuki HamajimaKazuo Tajima
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Jul 9, 2005·Molecular Carcinogenesis·Anne M LewisJoseph J Cullen
Jun 21, 2006·Chemical Biology & Drug Design·Steven L DixonShashidhar N Rao
Oct 3, 2006·Bioorganic & Medicinal Chemistry Letters·Karen A NolanRichard A Bryce
Dec 21, 2006·Journal of Korean Medical Science·Chang Gun ChoSang Yoon Kim
May 5, 2007·Journal of Chemical Information and Modeling·David A EvansMichael J Bodkin
Sep 30, 2008·Journal of Chemical Information and Modeling·Wei Deng, Christophe L M J Verlinde
Nov 7, 2008·Journal of Molecular Graphics & Modelling·Hongwu WangVincent S Madison
Jul 15, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Si Yeol SongEun Kyung Choi
Mar 5, 2010·Experimental & Molecular Medicine·Guang Zhi DongHeon Joo Park
Sep 2, 2010·Journal of Chemical Information and Modeling·Oliver KorbThomas E Exner
Aug 14, 2012·Journal of Biomolecular Structure & Dynamics·Periyasamy VijayalakshmiPitchai Daisy
Feb 7, 2014·Journal of Experimental & Clinical Cancer Research : CR·Yang YangLiyan Chen
Feb 18, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yonggang FanWei Wang
Oct 8, 2015·Accounts of Chemical Research·Elizabeth I Parkinson, Paul J Hergenrother
Sep 11, 2012·Journal of Chemical Theory and Computation·Bill R MillerAdrian E Roitberg
May 11, 2010·Journal of Chemical Theory and Computation·Devleena ShivakumarWoody Sherman
Jul 12, 2010·Molecular Informatics·Alexander Tropsha
Dec 15, 2016·Nature Communications·Eun-Taex OhHeon Joo Park
Jun 8, 2017·Journal of Biomolecular Structure & Dynamics·Chandrasekaran RamakrishnanM Michael Gromiha
Jun 24, 2017·Chemical Biology & Drug Design·Claudia López-LiraJorge Soto-Delgado
Jul 28, 2018·Journal of Biomolecular Structure & Dynamics·Yanqiu HuYaping Qiu
Dec 26, 2018·Journal of Biomolecular Structure & Dynamics·Richa AroraRita Kakkar

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Methods Mentioned

BETA
X-ray

Software Mentioned

GBSA
IFD
Prime Generalized Born Surface Area GBSA
SMARTS
qikProp
Schrodinger
Glide
PHASE
Pymol
AA

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