Study of potent CDK7 inhibitor secondary metabolites from Tecomella undulata

Abstract

Chemical investigation of the petroleum ether extract of heartwood of Tecomella undulata led to the isolation of tectonaquinone B (1), 2-methylquinizarin (2) along with tecomaquinone I (3), lapachol (4), 2-isopropenylnaphtho[2,3-b]-furan-4,9-quinone (5), dehydro-α-lapachone (6), α-lapachone (7), and β-lapachone (8). This is the first report of isolation of tectonaquinone B and 2-methylquinizarin from this plant. The structures of compounds were elucidated by advanced spectroscopic methods. Molecular docking study for potential inhibitory action toward CDK7 (cyclin-dependent kinase 7) were performed, which proved that these compounds have high binding affinities with the receptor protein (CDK7). 2-Methylquinizarin exhibited best docking score (−7.70 kcal/mol) among all the tested compounds. The present study showed that 2-methylquinizarin may exhibit potent anticancer activity through inhibiting CDK7 via interaction with Met94.

Graphical Abstract

Keywords:

• Tecomella undulata
• bignoniaceae
• isolation
• extraction
• CDK7
• docking

Acknowledgements

The authors are thankful to Dr. Amit Nargotra, Discovery Informatics Division, Indian Institute of Integrative Medicines, Jammu, for providing computational study facility. Venu Sharma and Barkha Darra Wadhwani would like to thank Department of Science and Technology, Government of India, for providing WOS-A project vide sanction no. SR/WOS-A/CS-46/2018 and SR/WOS-A/CS-24/2019 (G), respectively.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by DST, India.