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In‐silico Design of Safe and Effective Topoisomerase IB Inhibitors from Parent Compounds Isolated from Annona muricata
Author(s) -
Adeyemi Emmanuel Tofunmi,
James Ayorinde Babatunde,
Odeyemi Oluwatimilehin Ademilolani,
Magbagbeola Olubunmi Abiola
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb627
Subject(s) - topoisomerase , in silico , autodock , adme , stereochemistry , chemistry , lipinski's rule of five , dna , docking (animal) , rational design , computational biology , biochemistry , pharmacology , biology , in vitro , genetics , medicine , nursing , gene
Rational drug design using in‐silico tools have helped improve the time and possibilities of the development of safer drugs in recent times. This study was designed to develop safer DNA topoisomerase 1B inhibitors from two parent compounds isolated. The adsorption, distribution, excretion and toxicity (ADMET) properties of selected isoquinoline compounds were predicted using swiss ADME online tool. Analogues of these compounds were also created using ChemDraw professional Suite 16.0 by adding and removing functional groups based on the pharmacophoric structure of topotecan. 3D in‐silico docking was carried out between the designed compounds and the DNA topoisomerase 1B using AutoDock Vina software. Search space for ligand binding was defined and the program returned the binding affinities between the designed compounds and DNA topoisomerase 1B. Five analogues were designed for each compound. Out of the analogues designed, parent compound 1‐analogue 3 proved likely to be effective and safe in cancer treatment by having a binding affinity of −9.9 kcal/mol for DNA topoisomerase 1B and good ADMET prediction. The other compound (parent‐2) analogues had very high binding affinities for DNA topoisomerase 1B but they generally had ADMET problems. They were either predicted to be P‐glycoprotein substrates or blood‐brain barrier permeants. Rational drug design for anticancer agents from selected isoquinolines in Annona muricata predicted study compounds to be safe and effective in inhibiting DNA topoisomerase 1B. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .