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Drug Res (Stuttg) 2024; 74(05): 227-240
DOI: 10.1055/a-2305-2789
Original Article

Discovery of Substituted 2-oxoquinolinylthiazolidin-4-one Analogues as Potential EGFRK Inhibitors in Lung Cancer Treatment

Soniya Naik
1   Department of Pharmaceutical Chemistry, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India
2   Department of Pharmaceutical Chemistry, P.E.S’s Rajaram and Tarabai Bandekar College of Pharmacy, Farmagudi, Ponda, Goa, India
,
Vasu Soumya
1   Department of Pharmaceutical Chemistry, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India
,
Shivlingrao N Mamledesai
2   Department of Pharmaceutical Chemistry, P.E.S’s Rajaram and Tarabai Bandekar College of Pharmacy, Farmagudi, Ponda, Goa, India
,
M Manickavasagam
3   Department of Oncology, SRMC & RI, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India
,
Prafulla Choudhari
4   Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India
,
Sanket Rathod
4   Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra, India
› Author Affiliations Funding The research work is self-financed.
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Abstract

Purpose Cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. Globally, about 1 in 6 deaths is due to cancer and the chemotherapeutic drugs available have high toxicity and have reported side effects hence, there is a need for the synthesis of novel drugs in the treatment of cancer.

Methods The current research work dealt with the synthesis of a series of 3-(3-acetyl-2-oxoquinolin-1-(2H)-yl-2-(substitutedphenyl)thiazolidin-4-one (Va-j) derivatives and evaluation of their in-vitro anticancer activity. All the synthesized compounds were satisfactorily characterized by IR and NMR data. Compounds were further evaluated for their in-vitro anticancer activity against A-549 (lung cancer) cell lines. The in-vitro anticancer activity was based upon the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay method.

Results The synthesized compounds exhibited satisfactory anticancer properties against the A-549 cell line. The compound (Vh) showed the highest potency amongst the tested derivatives against the A-549 cell line with IC50 values of 100 µg/ml respectively and was also found to be more potent than Imatinib (150 µg/ml) which was used as a standard drug. Molecular docking studies of the titled compounds (Va-j) were carried out using AutoDock Vina/PyRx software. The synthesized compounds exhibited well-conserved hydrogen bonds with one or more amino acid residues in the active pocket of the EGFRK tyrosine kinase domain (PDB 1m17).

Conclusion Among all the synthesized analogues, the binding affinity of the compound (Vh) was found to be higher than other synthesized derivatives and a molecular dynamics simulation study explored the stability of the docked complex system.

Keywords

quinolin-2-one - thiazolidine - anticancer - lung cancer - docking - molecular dynamics - hydrogen bond - ADMET


Publication History

Received: 01 March 2024

Accepted: 02 April 2024

Article published online:
03 June 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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