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Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 54, 2024 - Issue 2
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Articles

Design, synthesis, and characterization of 3-(2-(pyrimidin-5-yl)thiazol-4-yl)-1,2,4-oxadiazole derivatives: Anticancer and molecular docking investigations

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Pages 144-157 | Received 14 Aug 2023, Published online: 26 Nov 2023
 

Abstract

Herein, we present a new library of 3-(2-(pyrimidin-5-yl)thiazol-4-yl)-1,2,4-oxadiazole (14a–j) as an anticancer agent designed based on in silico fragment-based drug design (FBDD). The derivatives were synthesized and characterized by 1HNMR,13CNMR, HRMS, and FT-IR. The library was named “pyrimidine-thiazole-1,2,4-oxadiazoles.” In addition, the MTT assay was used to test the compounds (14a–j) for their potential anticancer activity in a panel of four human cancer cell lines, such as PC3 & DU-145 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer), and the normal Vero cell lines, using the widely used anticancer drug etoposide acting as a reference drug and positive control. The value obtained was presented as IC50 (µM). The IC50 values of the reference standard ranged from 1.97 ± 0.45 µM to 3.08 ± 0.135 µM, while the library of tested compounds showed IC50 values ranging from 0.02 ± 0.0031 µM to 10.3 ± 6.25 µM. Among the tested compounds, six of them showed promising anticancer activity: 14a, 14b, 14c, 14d, 14e and 14j. Especially, one compound, 14a, showed excellent anticancer activity in all the tested cell lines. All compounds showed selective cytotoxicity against cancer cells but not against normal Vero cells (IC50 = >19 µM), justifying the designing approach to develop a selective anticancer agent. These compounds were also subjected to docking experiments to investigate potential binding site interactions, and the results were consistent with the in vitro results.

Graphical Abstract

Acknowledgments

The authors would like to thank the Manipal Academy of Higher Education for their unstinting support during the course of this study and Lupin Ltd, Pune, for providing a suitable basic research facility and funding. The author would like to express his gratitude to Dr. Venkata Palle, Mrs. Arnabi Marjit, Dr. Srikant Gorantala, Dr. Vijaya Desai, Mrs. Samiksha Daike for their phenomenal support throughout the Ph.D. course.

Disclosure statement

No potential conflict of interest was reported by the author(s).

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