Synthesis, Characterization and Anticancer Potential of the Selected Biginelli Hybrids and Their Nanocomposites

Abstract

Cancer is one of the most important health problems of today, which ranks second in the list of known deaths. Leukemia remains one of the most important health problems of today, ranking second among known causes of cancer-related death. Although there are treatments that can be effective, new targets and drugs with high selectivity and efficacy are still needed, particularly for non-solid tumors such as leukemia. Many reported antileukemic agents suffer from poor selectivity and bioavailability. Pyrimidines, as fundamental components of DNA and RNA, have attracted significant attention in drug discovery and development. Among the pyrimidine family, Biginelli-derived tetrahydropyrimidines (THPMs) hold particular importance due to their broad pharmacological potential, including anticancer activity. In this study, THPM molecules, and their nanocomposites were synthesized and characterized by NMR, elemental analysis, DSC, TGA, FTIR, MS, and subsequently assessed for their in vitro anticancer activities. The cytotoxic effects were assessed in K-562, THP-1, and MOLT-4 leukemia cell lines using the MTT assay. Results demonstrated that selected THPM derivatives exhibited potent and selective cytotoxicity in distinct leukemia subtypes: compounds 4b, 4e, 4j, and 4k were most active in CML (K-562) cells: 4c, 4e, and 4g in AML (THP-1) cells; and 4b, 4g, 4j, and 4k in ALL (MOLT-4) cells. The observed selectivity is likely driven by phenotypic and genotypic differences among leukemia cell lines, underscoring the therapeutic potential of THPM scaffolds as targeted antileukemic agents. These findings provide a strong basis for further mechanistic studies and preclinical evaluation.