Ultrasound-assisted green synthesis of triazole-based azomethine/thiazolidin-4-one hybrid inhibitors for cancer therapy through targeting dysregulation signatures of some Rab proteins

The overexpression of Rab proteins was linked to cancer development, making this family of proteins an attractive drug target for the identification of novel inhibitors against tumor diseases. In this study, novel triazole-based azomethine/thiazolidin-4-one hybrid analogs were designed, prepared and...

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Bibliographic Details
Published in:Green chemistry letters and reviews 2023-01, Vol.16 (1)
Main Authors: Abdelmonsef, Aboubakr H., El-Saghier, Ahmed M., Kadry, Asmaa M.
Format: Article
Language:English
Subjects:
anticancer
azomethine
docking study
hybrid molecules
Rab proteins
thiazolidin-4-one
Triazole
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Summary:The overexpression of Rab proteins was linked to cancer development, making this family of proteins an attractive drug target for the identification of novel inhibitors against tumor diseases. In this study, novel triazole-based azomethine/thiazolidin-4-one hybrid analogs were designed, prepared and structurally confirmed by using elemental and spectral techniques, these include FT-IR, MS, and NMR spectra. In addition, in vitro cytotoxic activity was assessed against NCI-60 cancer cell lines. To understand the possible mode of action and drugability, molecular docking studies and drug-likeness were achieved. The docking simulations were performed against various Rab family proteins Rab2a, Rab25, Rab5, and Rab35; promising targets for cancer medication to support the cytotoxicity findings and to further validate the action of new molecules. Furthermore, in silico ADMET screening of the molecules was within the recommended values stated by Lipinski's rule of five (Ro5), indicating their oral bioavailability and therapeutic potentials. Among the newly prepared analogs tested, compounds 4d and 3d exhibited significant antitumor activity against breast, ovarian, lung, and leukemia cancer cell lines. Our findings suggested that azomethine/thiazolidin-4-one moieties incorporated triazole analogs are a promising class of molecular entities for the development of new anticancer therapies, through targeting of some Rab proteins.
ISSN:1751-8253
1751-7192
DOI:10.1080/17518253.2022.2150394