ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Synthesis and anti-cancer evaluation of aminoacetylene maleimide hybrids

Bader A. Salameh, Ahmad M. Al-malkawi, Iman A. Mansi, Kayed Abu-Safieh, Murad A. AlDamen, and Bashaer Abu-Irmaileh

Department of Chemistry, Faculty of Science, The Hashemite University, Zarqa, Jordan

E-mail: bader@hu.edu.jo

Received: 15 February 2025  Accepted: 17 June 2025

Abstract:

A panel of 27 new compounds was prepared, starting from N-propargyl-3,4-dichloromaleimide where one chlorine atom was first replaced with either morpholine or piperidine. Then, the acetylenic moiety was subjected to a copper-catalyzed Mannich-type reaction to afford aminoacetylenic derivatives of maleimide. The prepared compounds' structures were characterized using IR, NMR, MS, and X-ray analysis (for compound 4 h). The newly synthesized compounds were evaluated for their cytotoxic activities against three cancer cell lines: MCF-7, MDA-MB-231, and K562. Ten compounds exhibited cytotoxic activity against one or two cell lines, among which 4c and 5c were active against all three cancer cell lines. Compounds 5e, 5 h, and 5c demonstrated excellent cytotoxicity against MCF-7 breast cancer cells. Compounds 5a, 5e, 5c, and 5d displayed moderate activity against leukemia (K562) cell lines, while compounds 4c and 4a showed good activity against metastatic breast cancer (MDA-MB-231) Additionally, compounds 5c and 4h exhibited moderate activity against MDA-MB-231.

Keywords: Maleimide; Aminoacetylene; Terminal alkyne; Mannich reaction

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-025-04196-0

Chemical Papers 79 (9) 6341–6353 (2025)