Synthesis and Pharmacophore Modelling of 2,6,9-Trisubstituted Purine Derivatives and Their Potential Role as Apoptosis-Inducing Agents in Cancer Cell Lines

Abstract

A series of 2,6,9-trisubstituted purine derivatives have been synthesized and investigated for their potential role as antitumor agents. Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine their potential effect on cell toxicity by the MTT method and flow cytometry analysis on four cancer cells lines and Vero cells. Three out of twelve compounds were found to be promising agents compared to a known and effective anticancer drug, etoposide, in three out of four cancer cell lines assayed with considerable selectivity. Preliminary flow cytometry data suggests that compounds mentioned above induce apoptosis on these cells. The main structural requirements for their activity for each cancer cell line were characterized with a preliminary pharmacophore model, which identified aromatic centers, hydrogen acceptor/donor center and a hydrophobic area. These features were consistent with the cytotoxic activity of the assayed compounds.

1H and 13C NMR spectral data of p‐nitrobenzenesulfonamides and dansylsulfonamides derived from N‐alkylated o‐(purinemethyl)anilines

“…Adenine derivatives (4,8,9) exhibit different characteristics in their 1 H spectra in relation to those of the purines 1-3, 5-7. Pronounced downfield shifts are observed (Table 1) The 13 C NMR signals for C-4 5FU , C-5 5FU and C-6 5FU in 10 should be highlighted.…”

“…In recent years, purine bases have been the subject of extensive research that led to the discovery of thousands of biological active compounds, including antineoplastic ones. [1][2][3][4][5][6] We synthesized a novel series of alkylated purines (1)(2)(3)(4)(5)(6)(7)(8)(9) with notable in vitro anti-proliferative activities, low toxicity and systemic distribution after oral administration in vivo. [1] The design of these compounds was based on the modifications of acyclic O,N-acetals, previously described by our research group as anti-proliferative agents.…”

Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays

“…We synthesized new 2,6,9-trisubstituted purines 4a-k (Series I), 4l-u (Series II), and 7a-j (Series III), using short, simple, and efficient synthetic methods as described in Schemes 1 and 2 [22,34,35]. We obtained 21 compounds of Series I and II in three steps using 2-fluoro-6-chloropurine (1) as a starting material.…”

“…Interestingly this fragment is part of the purine core, which is considered a privileged scaffold in medicinal chemistry [16][17][18][19]. For this reason, a large number of purine derivatives have been synthetized and their antitumor activity has been reported [20][21][22][23]. Compounds I [24] and II [25] (Figure 2) are examples of di-and tri-substituted purine derivatives that have already been tested against cancer cells.…”

Cytotoxic of Ganoderma lucidum in Colon Cancer through Cyclooxygenase 2 (COX-2) as Its Molecular Target

“…Cytotoxic assay towards Vero cells as well as WiDr cells were designed based on our previous studies [45][46]. Cells were seeded in a culture tissue flask until 80% confluent, then 5×10 3 cells were planted into a 96-well micro plate.…”