One-pot synthesis of tetrahydropyrimidinecarboxamides enabling in vitro anticancer activity: a combinative study with clinically relevant brain-penetrant drugs

In this study, we describe a one-pot three-component synthesis of bioactive tetrahydopyrimidinecarboxamide derivatives employing lanthanum triflate as a catalyst. Out of the synthesized compounds, 4f had the most potent anti-cancer activity and impeded cell cycle progression effectively. Anti-cancer...

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Bibliographic Details
Published in:RSC advances 2024-08, Vol.14 (37), p.27174-27186
Main Authors: Upadhyay, Dipti B, Nogales, Joaquina, Mokariya, Jaydeep A, Vala, Ruturajsinh M, Tandon, Vasudha, Banerjee, Sourav, Patel, Hitendra M
Format: Article
Language:English
Subjects:
Anticancer properties
Biocompatibility
Biological activity
Chemical synthesis
Chemistry
Growth factors
Kinases
Lanthanum
Lead compounds
Stem cells
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Summary:In this study, we describe a one-pot three-component synthesis of bioactive tetrahydopyrimidinecarboxamide derivatives employing lanthanum triflate as a catalyst. Out of the synthesized compounds, 4f had the most potent anti-cancer activity and impeded cell cycle progression effectively. Anti-cancer bioactivity was observed in 4f against liver, breast, and lung cancers as well as primary patient-derived glioblastoma cell lines. Compound 4f effectively inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. Specifically, 4f exhibited synergistic cytotoxicity with the EGFR inhibitor that is the clinical epidermal growth factor receptor inhibitor osimertinib. 4f does not exhibit anti-kinase activity and is cytostatic in nature, and further work is needed to understand the true molecular target of 4f and its derivatives. Through our current work, we establish a promising tetrahydopyrimidinecarboxamide-based lead compound with anti-cancer activity, which may exhibit potent anti-cancer activity in combination with specific clinically relevant small molecule kinase inhibitors.
ISSN:2046-2069
2046-2069
DOI:10.1039/d4ra04171b