Molecular docking, PKPD, and assessment of toxicity of few chalcone analogues as EGFR inhibitor in search of anticancer
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ORIGINAL RESEARCH
Molecular docking, PKPD, and assessment of toxicity of few chalcone analogues as EGFR inhibitor in search of anticancer agents PurraBuchi Reddy 1 & M. B. Madhusudhana Reddy 1 & Ramkrishna Reddy 1 & Santosh Chhajed 2 & Pramodkumar P. Gupta 3 Received: 6 April 2020 / Accepted: 19 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In the present work, molecular docking of the chalcone analogues with receptor EGFR carried out using erlotinib as reference drug is reported. About 15 chalcone analogues were analyzed CHL(1–15). Molecules CHL2, CHL3, CHL9, CHL11, and CHL15 found strong affinity for receptor EGFR exhibiting binding energies − 7.7 kcal/mol, − 7.5 kcal/mol, − 7.6 kcal/mol, − 7.9 kcal/mol, and − 8.1 kcal/mol, respectively, when erlotinib a reference drug exhibits binding energy − 7.6 kcal/mol. Toxicity for molecules was assessed against the cytochromes P450 (CYP) and P-gp using Swiss ADMET. Molecule CHL9 could be a suitable lead compound inhibitor to CYP1A2 followed by CHL2 inhibitor of CYP1A2 and CYP2C9 and CHL15 with a most stable binding affinity of − 8.1 kcal/mol, inhibiting CYP1A2, CYP2C19, and CYP2D6. CHL3 has a binding affinity of − 7.5 kcal/mol, inhibiting all the 05 CYP enzymes (CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4). CHL11 has a binding affinity of − 7.9 kcal/mol, inhibiting CYP1A2, CYP2C19, and CYP2C9. Considering inhibition of CYP family enzymes by molecules, further here we have perform the enrichment analysis to these CYP family enzymes and reported the metabolic pathways which were probably affected by inhibition of these enzymes using EnrichR online enrichment analysis server. The current predictions over these 15 chalcone derivatives will be needed to further investigate in vivo and in vitro conditions to identify the optimum therapeutic efficacy and least toxicity. Keywords Molecular docking . PKPD . Toxicity . EGFR inhibitor . Anticancer agents
Introduction Introduction is one of the important pharmacophore precursors of isoflavonoids and flavonoids. Chalcones are present in many edible plants. These comprise one of the main classes of small molecules which are naturally occurring exhibiting promising anticancer activity. Several research groups have focused on the antitumor activity of these compounds. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11224-020-01571-3) contains supplementary material, which is available to authorized users. * PurraBuchi Reddy [email protected] 1
Department of Chemistry, Reva University, Bengaluru, Karnataka, India
2
Department of Pharmaceutical Chemistry, MET’s Institute of Pharmacy, Nashik, India
3
School of Biotechnology and Bioinformatics, D Y Patil Deemed to be University, CBD Belapur, Navi Mumbai, Maharashtra, India
Chalcones are reported as one of the useful anticancer motif exhibiting potential activity for various cell lines like breast cancer and prostate cancer at nanomolar concentrations [1]. Newer compounds synthesized chalcone f
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