A computational molecular docking study of camptothecin similars as inhibitors for topoisomerase 1
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ORIGINAL RESEARCH
A computational molecular docking study of camptothecin similars as inhibitors for topoisomerase 1 Atidel Boudjedir 1,2 & Khaireddine Kraim 1,2 & Youcef Saihi 1,2 & Ouassila Attoui-Yahia 1 & Fouad Ferkous 1 & Abdelmalek Khorief Nacereddine 2 Received: 12 March 2020 / Accepted: 3 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract DNA topoisomerase 1 (Top1) is a prime target of chemotherapy agents and a crucial enzyme that maintains DNA topology, during transcription, replication, repair, and recombination by relaxing DNA torsional strain through reversible DNA singlestrand breaks process. Top1 is a selective target of camptothecin (CPT), a natural alkaloid compound and an important class of anti-cancer drugs, that reversibly bind the covalent DNA–Top1 complex, slowing down the religation of the cleaved DNA strand, thus inducing cell death. However, the use of CPTs was hampered by several drawbacks. In the present study, we have performed a receptor-ligand molecular docking analysis of a set of 738 camptothecin-like molecules in order to identify new potential derivative structures of camptothecin, a more potent anticancer agent with better efficacy, less toxicity, and side effects. MolDock score and hydrogen bonding interactions are the parameters used for docking studies. The inhibition phenomenon is mainly governed by various non-covalent interactions, including hydrogen bonds, steric interactions, and van der Waals interactions between the DNA basis and ligand. Among the top 10 ranked molecules, all the CPT similar ligands were found to have higher binding affinity in comparison with the CPT of the human DNA–Top1. The first ranked molecule (21882279) showed the highest docking score value (− 229.993 kcal/mol) which it binds to the cavity by Arg364 residue. These results suggest that similar ligands may serve as a leading compound for the development of anticancer agents. Keywords Topoisomerase 1 . Cancer . Camptothecin . Molecular docking
Introduction Cancer is a pathological term commonly used in describing several diseases that can affect on various vital parts of the body through inducing abnormal cell proliferation in normal tissues. All the affected cells are resulted from the same clone, in which the initiator cancer cells receive some characteristics, making them able to divide indefinitely and to form Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11224-020-01633-6) contains supplementary material, which is available to authorized users. * Abdelmalek Khorief Nacereddine [email protected] 1
Laboratory of Applied Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Badji-Mokhtar Annaba, BP 12, 23000, Annaba, Algeria
2
Department of Physics and Chemistry, Higher Normal School of Technological Education-Skikda, Azzaba, Skikda, Algeria
metastases [1]. Thus, today, the need to develop more potent and selective antitumor agents remains a major concern and a challenge
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