Title:Synthesis, In vitro, and Docking Analysis of C-3 Substituted Coumarin Analogues as Anticancer Agents
Volume: 17
Issue: 2
Author(s): Anuradha Thakur, Kamalpreet Kaur, Praveen Sharma, Ramit Singla, Sandeep Singh and Vikas Jaitak*
Affiliation:
- Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Bathinda 151 001,India
Keywords:
Coumarin, anticancer, breast cancer, estrogen receptor, molecular docking, ADME.
Abstract:
Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women
next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current
anticancer agents have several drawbacks such as serious side effects and the emergence of resistance
to chemotherapeutic drugs. As coumarins possess minimum side effects along with multidrug
reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways
that can be explored for selective anticancer activity.
Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on
human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds
for ER-α target protein by molecular docking.
Methods: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17)
has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions
and ADME study of the compounds were analyzed by using Schrodinger software.
Results: Among the synthesized analogues, 12 and 13 show good antiproliferative activity with
IC50 values 1 and 1.3 μM, respectively. Molecular docking suggests a remarkable binding pose of
all the seventeen compounds. Compounds 12 and 13 were found to exhibit a docking score of -4.10
kcal/mol and -4.38 kcal/mol, respectively.
Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties
of all compounds were in the acceptable range. The active compounds can be taken for lead
optimization and mechanistic interventions for their in vivo study in the future.
