The Thai Journal of Pharmaceutical Sciences
Abstract
Background: Lung cancer is alarmingly increasing and therapies targeting receptors such as human epidermal growth factor have been found to be emerging in treating lung cancer. Many studies report azetidinone bearing compounds to be cytotoxic. This work aims to prove the anti-lung cancer action of synthesized azetidinones that are through epidermal growth factor receptor (EGFR) inhibition. Materials and Methods: Novel azetidinone derivatives were synthesized from Schiff bases; molecular docking analyzed the interactions with EGFR, and pharmacophore modeling revealed the features responsible for the possible interactions. Moreover, the compounds with good docking scores were selected for anti-lung cancer study by MTT assay. Results: The compounds 4c, 5a, and 6c have scored better docking scores with indole hydrazide, napthoic hydrazide, and 4-chloro hydrazide groups, respectively. At 250 μM, the tested azetidinones, 4c, 5a, and 5d, exhibited the highest activity against lung cancer cells in contrast with the standard. The pharmacophore modeling predicted the groups responsible for the formation of hydrogen bonding. Conclusion: In this work, the synthesized azetidinones were screened for their anticancer activities and EGFR interaction. Moreover, it confirms that it could effectively inhibit the EGFR receptors in lung cancer cells and can act as potential anticancer leads and might consider for the future studies.
Publisher
Faculty of Pharmaceutical Sciences, Chulalongkorn University
First Page
595
Last Page
606
Recommended Citation
James, Jainey P.; Aiswarya, T. C.; Shenoy, Swetha P.; and Devaraji, Vinod
(2022)
"Synthesis and in silico study of new azetidinones against non-small cell lung cancer by EGFR inhibition,"
The Thai Journal of Pharmaceutical Sciences: Vol. 46:
Iss.
5, Article 13.
Available at:
https://digital.car.chula.ac.th/tjps/vol46/iss5/13