Synthesis of novel substituted purine derivatives and identification of the cell death mechanism

Abstract

Novel 9-(substituted amino/piperazinoethyl)adenines (4-12), 6-(substituted piperazino/amino)purines (15-27), 9-(p-toluenesulfonyl/cyclopentyl/ethoxycarbonylmethyl)-6-(substituted amino/piperazino)purines (28-34, 36, 37, 38-41) were synthesized and evaluated initially for their cytotoxic activities on liver Huh7, breast T47D and colon HCT116 carcinoma cells. N(6)-(4-Trifluoromethylphenyl)piperazine derivative (17) and its 9-(p-toluene-sulfonyl)/9-cyclopentyl analogues (28, 36) had promising cytotoxic activities. Compounds 17, 28 and 36 were further analysed for their cytotoxicity in a panel of a liver cancer cell lines. The compound 36 had better cytotoxic activities (IC50 ≤ 1 μM) than the nucleobase 5-FU and nucleosides fludarabine, cladribine, and pentostatine on Huh7 cells. Cytotoxicity induced by 36 was later identified as senescence associated cell death by SA-β-Gal assay.

Design, Synthesis and In Vitro Cytotoxic Activity of New 6,9-Disubstituted Purine Analogues

“…In recent years, purine analogues, which are Hsp90 inhibitors, have entered clinical trials as drugs in the therapy of solid tumors and hematologic malignancies. 50 In our previous studies, 51,52 we have reported important cytotoxic activities of 9-(cyclopentyl/β-D-ribofuranosyl/para-toluenesulfonyl)-6-(4-substituted piperazino)purine analogs A, B, C ( Figure 2). In this work, we report the synthesis of new analogs of purines A, B, C as 9-(4-substituted benzyl)purines and evaluate their cytotoxic activities against liver (Huh7), colon (HCT116) and and breast (T47D) carcinoma cell lines.…”

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

“…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. Both of these derivatives show anticancer activity on some cancer cell lines with sub-micromolar IC 50 values, and are therefore considered as potential drug candidates.…”

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

“…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.…”