Title:In Silico Structure-based Screening of Potential Anticancer Bioactive Natural Constituents from African Natural Products
Volume: 21
Issue: 16
Author(s): Khairedine Kraim*, Atidel Boudjedir, Youcef Saihi, Fatima Zohra Oueld Chikh, Yassira Slatnia and Fouad Ferkous
Affiliation:
- Laboratory of Physical Chemistry and Biology of Materials, Department of Physics and Chemistry, Higher Normal
School of Technological Education, Skikda, Algeria
- Laboratory of Applied Organic Chemistry, Department of
Chemistry, University of Badji Mokhtar, Annaba, Algeria
Keywords:
Natural products, African natural products database, molecular docking, Virtual screening, topoisomerase 1, cancer.
Abstract:
Introduction: Inhibitors of topoisomerases, essential regulators of cancer development,
are promising as cancer treatments. These enzymes regulate DNA topology and eliminate topological
constraints during various biological processes, including replication, transcription, and recombination.
Nature has continually offered scientists pathways to explore the development of new drugs.
Indeed, since ancient times, various plant extracts have been utilized in treating multiple pathologies.
Objective: It’s intriguing to diversify the therapeutic classes of natural topoisomerase 1 inhibitors.
We aimed to explore the relationship between the toxicity of certain medicinal plants in North Africa
and their anti-topoisomerase 1 enzyme activity. This investigation aims to discover potentially valuable
compounds for fighting cancer by inhibiting the Topo1 enzyme, enriching the anticancer therapeutic
class.
Methods: This study has conducted a virtual screening of the African Natural Products Database to
identify new scaffolds as topoisomerase 1 inhibitors. Molecular docking as a structure-based drug
design approach was selected as one of the best approaches, and the complex code ID: 1K4T was
used for this purpose.
Results and Discussion: The molecular docking of more than 5790 natural products extracted from
this database was docked into the binding site of the above-cited complex using the Modlock optimizer
and Moldock score as search and scoring function algorithms, respectively. The top-ranked
compounds have been assessed, analyzed, and compared to Topotecan and Irinotecan as reference
ligands and drugs.
Conclusion: Consequently, the seven natural products have shown a strong affinity to topoisomerase
1 and DNA. They establish a clear link between topoisomerase 1 inhibition and the anticancer activity
of their corresponding plant extracts. Therefore, these hits are promising and serve as a base for
further development of new topoisomerase 1 inhibitors.
