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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

Rationalization of the activity Profile of Pyruvate Kinase Isozyme M2 (PKM2) Inhibitors using 3D QSAR

Author(s): Merugumala Kusuma, Sahil Arora, Sourav Kalra, Anuhar Chaturvedi, Michael Heuser and Raj Kumar*

Volume 21 , Issue 25 , 2021

Published on: 04 August, 2021

Page: [2258 - 2271] Pages: 14

DOI: 10.2174/1568026621666210804124555

Price: $65


Introduction: Pyruvate kinase isozyme M2 (PKM2) was observed to be overexpressed and play a key role in cell growth and cancer cells' metabolism. During the past years, phytochemicals have been developed as new treatment options for chemoprevention and cancer therapy. Natural resources, like shikonin (naphthoquinone) and its derivatives, have emerged to be high potential therapeutics in cancer treatment.

Methods: Our study aimed to design novel anti-tumour agents (PKM2 inhibitors) focusing on the shikonin scaffold with a better activity using computational methods. We applied a three-dimensional quantitative structure-activity relationship (3D-QSAR) approach using Field-based QSAR.

Results: The Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) were performed on a series of forty shikonin derivatives, including shikonin, to develop robust models and rationalize the PKM2 inhibitory activity profile by building a correlation between structural features and activity.

Conclusion: These predictive computational models will further help the design and synthesis of potent PKM2 inhibitors and their fast biological assessment at a low cost.

Keywords: PKM2 inhibitors, Shikonin derivatives, 3D QSAR, Cancer, Field-based QSAR, CoMFA, CoMSIA.

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