Purine Scaffold in Agents for Cancer Treatment

Abstract

Cancer represents one of the most important and often fatal threats in the human population. Regarding the natural products, the purine scaffold appears in the purine bases in nucleic acids. Purine and its natural derivatives display a number of pharmacological effects. Previous investigations revealed that different compounds bearing the purine scaffold in their molecules belong to a group of potent agents for cancer treatment. Therefore, this review focuses on summarizing recently designed agents for potential cancer treatment bearing the purine scaffold as the key structural motif in the molecules. The reviewed structures clearly show the advantages and disadvantages of different substituents of the key scaffold that affect the final cytotoxic effects of the studied structures. The structure-activity relationship analysis shows a summary of different but potent compounds mentioned in this review and identifies the compounds receiving priority importance due to their high cytotoxicity and exceptional physicochemical characteristics. The effects of metal coordination, the formation of convenient conjugated molecules, and supramolecular self-assembly resulting in the production of biologically active nanovesicles and other nanoassemblies are also demonstrated. The reviewed original studies clearly showed the possible advantages of (a) metal ion coordination, (b) the formation of conjugates, and (c) designing smart and biocompatible nanoassemblies for biological activity in comparison with the characteristics of the parent compounds. This review is based on the most recent articles published in the last two years, 2023-2024, and it represents work with a highly interdisciplinary nature. Even if these original articles are not too numerous within the given period, the investigations published therein have clearly documented the importance of the purine scaffold in pharmacology and in medicinal and supramolecular chemistry.

Figure 1

Structures of compounds 1a–1q.

Figure 2

Structures of compounds 2a–2g.

Figure 3

Structures of compounds 3a–3e.

Figure 4

Structures of compounds 4a–4i.

Figure 5

Structures of compounds 5a–5r.

Figure 6

Structures of roscovitine and compounds 6a–6c.

Figure 7

Structures of compounds 7a–7j.

Figure 8

Structures of compounds 8a–8f.

Figure 9

Scheme of the synthesis of fludarabine complexes 9c–9f, using fludarabine (9a) as a source molecule.

Figure 10

Structures of compounds 10a–10l.

Figure 11

Structures of compounds 11a–11h.

Figure 12

General structures of 12a–12c.

Figure 13

Structures of compounds 13a–13c.

Figure 14

Structure of the most active compound 14a accompanied by several other structures (14b–14g) that differ from 14a by the structure of the linker drawn in the red color and either pomalidomide or the VHL ligand drawn in the blue color as the ligands for E3-ligase recruitment. The ligand for E3-ligase recruitment in 14d is methyl pomalidomide, and the compound was used as a negative control.