Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR
Joint Authors
Shaik, Nur Ahmad
al-Kreathy, Huda M.
Ajabnoor, Ghadah M.
Verma, Prashant Kumar
Banaganapalli, Babajan
Source
Saudi Journal of Biological Sciences
Issue
Vol. 26, Issue 3 (31 Mar. 2019), pp.439-448, 10 p.
Publisher
Publication Date
2019-03-31
Country of Publication
Saudi Arabia
No. of Pages
10
Main Subjects
Topics
Abstract EN
The somatic mutations in ATP binding cleft of the tyrosine kinase binding domain of EGFR are known to occur in 15–40% of non-small cell lung cancer (NSCLC) patients.
Although first and second generation anti-EGFR inhibitors are widely used to treat these patients, their therapeutic efficacy is modest and often results in adverse effects or drug resistance.
Therefore, there is a need to develop novel as well as safe anti-EGFR drugs.
The rapid emergence of computational drug designing provided a great opportunity to both discover and predict the efficacy of novel EGFR inhibitors from plant sources.
In the present study, we designed several chemical analogues of edible curcumin (CUCM) compound and assessed their drug likeliness, ADME and toxicity properties using a diverse range of advanced computational methods.
We also have examined the structural plasticity and binding characteristics of EGFR wild-type and mutant forms (S769L and K846R) against ligand molecules like Gefitinib, native CUCM, and different CUCM analogues.
Through multidimensional experimental approaches, we conclude that CUCM-36 ((1E,4Z,6E)-1- (3,4-Diphenoxyphenyl)-5-hydroxy-7-(4-hydroxy-3-phenoxyphenyl)-1,4,6-heptatrien-3-one) is the best anti-EGFR compound with high drug-likeness, ADME properties, and low toxicity properties.
CUCM-36 compound has demonstrated better affinity towards both wild-type (DG is 8.5 kcal/Mol) and mutant forms (V769L & K846R; DG for both is >9.20 kcal/Mol) compared to natural CUCM and Gefitinib inhibitor.
This study advises the future laboratory assays to develop CUCM-36 as a novel drug compound for treating EGFR positive non-small cell lung cancer patients.
American Psychological Association (APA)
Shaik, Nur Ahmad& al-Kreathy, Huda M.& Ajabnoor, Ghadah M.& Verma, Prashant Kumar& Banaganapalli, Babajan. 2019. Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR. Saudi Journal of Biological Sciences،Vol. 26, no. 3, pp.439-448.
https://search.emarefa.net/detail/BIM-887221
Modern Language Association (MLA)
Shaik, Nur Ahmad…[et al.]. Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR. Saudi Journal of Biological Sciences Vol. 26, no. 3 (Mar. 2019), pp.439-448.
https://search.emarefa.net/detail/BIM-887221
American Medical Association (AMA)
Shaik, Nur Ahmad& al-Kreathy, Huda M.& Ajabnoor, Ghadah M.& Verma, Prashant Kumar& Banaganapalli, Babajan. Molecular designing, virtual screening and docking study of novel curcumin analogue as mutation (S769L and K846R) selective inhibitor for EGFR. Saudi Journal of Biological Sciences. 2019. Vol. 26, no. 3, pp.439-448.
https://search.emarefa.net/detail/BIM-887221
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references : p. 447-448
Record ID
BIM-887221