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RESEARCH ARTICLE
Contents Vol 75(4)

The art of design in azlactone–benzoxazinone chemistry, docking studies and in vitro cytotoxicity evaluation

Shadi Dadkhah A , Mahla Malekzadeh A , Farshid Hassanzadeh A , Ghadamali Khodarahmi A , Parvin Asadi A and Mahboubeh Rostami https://orcid.org/0000-0001-9968-821X A *
+ Author Affiliations
- Author Affiliations

A Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

* Correspondence to: m.rostami@pharm.mui.ac.ir

Handling Editor: Charlotte Williams

Australian Journal of Chemistry 75(4) 312-323 https://doi.org/10.1071/CH21275
Submitted: 24 October 2021  Accepted: 17 January 2022   Published: 16 March 2022

© 2022 The Author(s) (or their employer(s)). Published by CSIRO Publishing.

Abstract

In this study, by combining azlactone–benzoxazinone chemistry, we synthesized new hybrid compounds and evaluated the in vitro cytotoxicity on the breast cancer cell line. The desired compounds were synthesized using green and straightforward chemical reactions on azlactone and benzoxazinone structures through simple ring closure and nucleophilic ring-opening reactions. Preliminary in vitro cytotoxic results on the MCF-7 breast cancer cell line showed that the synthesized compounds have excellent anticancer activity with interestingly low inhibitory concentrations (IC50s in the range of 8–20 mM). Fortunately, our structures simultaneously had low toxicity on the normal HUVEC cell line. Finally, molecular docking studies were performed on the EGFR enzyme as one of the active signaling pathways in cancer cells for the best cytotoxic candidates. In this regard, the alignment of the docking and cytotoxicity results was interesting. In conclusion, these potential cytotoxic compounds could be considered in further studies.

Keywords: anti-cancer activity, azlactone, benzoxazinone, docking study, imidazolone, in vitro cytotoxicity, quinazolone.


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