Angular Regioselective Synthesis of Varied Functionalized Hexahydro-1,2,4-triazolo[4,3- a]quinazolin-9-ones and Their Antiproliferative Action

Awad I Said; Márió Gajdács; István Zupkó; Matti Haukka; Márta Palkó

doi:10.3390/molecules28093718

Angular Regioselective Synthesis of Varied Functionalized Hexahydro-1,2,4-triazolo[4,3- a]quinazolin-9-ones and Their Antiproliferative Action

Molecules. 2023 Apr 25;28(9):3718. doi: 10.3390/molecules28093718.

Authors

Awad I Said^{1

2}, Márió Gajdács³, István Zupkó³, Matti Haukka⁴, Márta Palkó¹

Affiliations

¹ Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
² Chemistry Department, Faculty of Science, Assiut University, Assiut 71516, Egypt.
³ Institute of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
⁴ Department of Chemistry, University of Jyväskulä, FIN-40014 Jyväskulä, Finland.

Abstract

New 2-thioxopyrimidin-4-ones capable of participating in regioselective reactions with functionally diverse hydrazonoyl chlorides towards angular regioisomers, rather than linear ones, were designed and synthesized to form stereoisomeric cis- and trans-hexahydro [1,2,4]triazolo[4,3-a]quinazolin-9-ones to be tested as antitumor candidates. The angular regiochemistry of the products was verified through crystallographic experiments and NMR studies. In addition, the regioselectivity of the reaction was found to be independent of the stereochemistry of the used 2-thioxopyrimidin-4-one. Only compound 4c demonstrated satisfactory growth inhibition against all the cancer cells used among all the produced drugs.

Keywords: [1,2,4]triazolo[4,3-a]quinazolin-9-ones; antitumor action; hydrazonoyl chloride; regioselective synthesis.

Grants and funding

The authors’ thanks are due to the Hungarian Research Foundation (OTKA No. K-138871) and the Ministry of Human Capacities, Hungary grant, TKP-2021-EGA-32. Project no. TKP2021-EGA-32 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme.