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Volume 8
Medicinal Chemistry
ISSN: 2161-0444
Medicinal Chemistry 2018
June 14-15, 2018
June 14-15, 2018 | Barcelona, Spain
10
th
World Congress on
Medicinal Chemistry and Drug Design
Molecular docking study and structure-based design of novel camptothecin analogues used as
topoisomerase I inhibitor
David Ebuka Arthur
Ahmadu Bello University, Nigeria
T
his paper involves the molecular docking study on the inhibition of Human topoisomerase I (top1) which is the molecular
target of a diverse set of anti-cancer compounds by Glycinate, camptothecin and its analogs. Their reaction mechanisms
involving their interaction to a transient top1-DNA covalent complex, in order to inhibit the resealing of a single-strand nick
created by the enzyme to relieve superhelical tension in duplex DNA, were confirmed using Quantumcomputational techniques
in ICM-Pro Molsoft program. Our research findings on this reaction inquiry of the human top1-DNA complex bound with
camptothecin analogs were helpful in improving the activities of top1 poisons through a structure based computational drug
design. our results indicate that the Pi-Pi interactions of the camptothecin drugs with DNA as a result of its planner nature
and the presence of some fragments on the lactone E-ring were directly responsible for its stable ternary complex with topo 1.
The molecular docking result of our study shows Morpholinodoxorubicin (-32.835 kcal/mol), 9-Amino-20-RS-Camptothecin
(-28.792 kcal) and Camptothecin Lysinate HCl (-28.224 kcal) best inhibit topo 1 when compared with other NSC compounds
within our data set. These compounds were further utilized in designing new potent antitumor compounds by attaching potent
fragments to the lactone ring of the compounds. Most of these compounds were reported to be more active than the parent
structure, some of which includes CLD-12, CLD-7, CD-9 with a binding affinity of -40.307kcal/mol, -36.743kcal/mol and
-36.072kcal/mol respectively. At the end of our study, we were able to optimize potent novel compounds that can be used to
inhibit topoisomerase 1 enzyme.
davidebukaarthur@gmail.comMed chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-040