Evaluation of drug candidature: In silico ADMET, binding interactions with CDK7 and normal cell line studies of potentially anti-breast cancer enamidines.
| Title: | Evaluation of drug candidature: In silico ADMET, binding interactions with CDK7 and normal cell line studies of potentially anti-breast cancer enamidines. |
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| Authors: | Bansode P; Department of Chemistry, Shivaji University, Kolhapur, 416004, M.S., India.; Anantacharya R; Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur, 577548, Karnataka, India.; Dhanavade M; Department of Microbiology, Shivaji University, Kolhapur, 416004, M.S., India.; Kamble S; Department of Microbiology, Shivaji University, Kolhapur, 416004, M.S., India.; Barale S; Department of Microbiology, Shivaji University, Kolhapur, 416004, M.S., India.; Sonawane K; Department of Microbiology, Shivaji University, Kolhapur, 416004, M.S., India.; Satyanarayan ND; Department of Pharmaceutical Chemistry, Kuvempu University, Post Graduate Centre, Kadur, 577548, Karnataka, India.; Rashinkar G; Department of Chemistry, Shivaji University, Kolhapur, 416004, M.S., India. Electronic address: gsr_chem@unishivaji.ac.in. |
| Source: | Computational biology and chemistry [Comput Biol Chem] 2019 Dec; Vol. 83, pp. 107124. Date of Electronic Publication: 2019 Sep 14. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: England NLM ID: 101157394 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-928X (Electronic) Linking ISSN: 14769271 NLM ISO Abbreviation: Comput Biol Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Elsevier; Original Publication: Oxford : Pergamon, c2003- |
| MeSH Terms: | Computer Simulation*; Amines/*pharmacology ; Antineoplastic Agents/*pharmacology ; Azides/*pharmacology ; Breast Neoplasms/*drug therapy ; Cyclin-Dependent Kinases/*antagonists & inhibitors ; Pargyline/*analogs & derivatives ; Protein Kinase Inhibitors/*pharmacology; Amines/chemical synthesis ; Amines/chemistry ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Azides/chemical synthesis ; Azides/chemistry ; Binding Sites/drug effects ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cyclin-Dependent Kinases/chemistry ; Cyclin-Dependent Kinases/metabolism ; Pargyline/chemical synthesis ; Pargyline/chemistry ; Pargyline/pharmacology ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/chemistry ; Animals ; Chlorocebus aethiops ; Drug Screening Assays, Antitumor ; Female ; Humans ; Hydrogen Bonding ; MCF-7 Cells ; Molecular Docking Simulation ; Molecular Structure ; Vero Cells ; Cyclin-Dependent Kinase-Activating Kinase |
| Abstract: | We have recently explored novel class of potentially anti-breast cancer active enamidines in which four molecules 4a-c and 4h showed higher anticancer activity compared to standard drug doxorubicin. As a part of extension of this work, we have further evaluated in silico cheminformatic studies on bioactivity prediction of synthesized series of enamidines using mole information. The normal cell line study of four lead compounds 4a-c and 4h against African green monkey kidney vero strain further revealed that the compounds complemented good selectivity in inhibition of cancer cells. The in silico bioactivity and molecular docking studies also revealed that the compounds have significant interactions with the drug targets. The results reveal that enamidine moieties are vital for anti-breast cancer activity as they possess excellent drug-like characteristics, being potentially good inhibitors of cyclin dependent kinases7 (CDK7).; (Copyright © 2019 Elsevier Ltd. All rights reserved.) |
| Contributed Indexing: | Keywords: ADMET; CDK7; Cancer; Cytotoxicity; Docking; Doxorubicin |
| Substance Nomenclature: | 0 (Amines); 0 (Antineoplastic Agents); 0 (Azides); 0 (Protein Kinase Inhibitors); 9MV14S8G3E (Pargyline); EC 2.7.11.22 (Cyclin-Dependent Kinases); F3H7ZXK9ZU (propargyl bromide); EC 2.7.11.22 (Cyclin-Dependent Kinase-Activating Kinase) |
| Entry Date(s): | Date Created: 20190929 Date Completed: 20191219 Latest Revision: 20221207 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.compbiolchem.2019.107124 |
| PMID: | 31563021 |
| Database: | MEDLINE |
Journal Article