Synthesis of novel 6-substituted amino-9-(beta-D-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells

Kucukdumlu, Asligul
Guven, Ebru Bilget
Altiparmak, Duygu
Atalay, Rengül
New nucleoside derivatives with nitrogen substitution at the C-6 position were prepared and screened initially for their in vitro anticancer bioactivity against human epithelial cancer cells (liver Huh7, colon HCT116, breast MCF7) by the NCI-sulforhodamine B assay. N-6-(4-trifluoromethylphenyl) piperazine analog (27) exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC50 = 1-4 mu M) than 5-FU, fludarabine on Huh7, HCT116 and MCF7 cell lines. The most potent nucleosides (11, 13, 16, 18, 19, 21, 27, 28) were further screened for their cytotoxicity in hepatocellular cancer cell lines. The compound 27 demonstrated the highest cytotoxic activity against Huh7, Mahlavu and FOCUS cells (IC50 = 1, 3 and 1 mu M respectively). Physicochemical properties, drug-likeness, and drug score profiles of the molecules showed that they are estimated to be orally bioavailable. The results pointed that the novel derivatives would be potential drug candidates.


Synthesis of Some Substituted 6-Phenyl Purine Analogues and Their Biological Evaluation as Cytotoxic Agents
Kucukdumlu, Asligul; Tuncbilek, Meral; Guven, Ebru Bilget; Atalay, Rengül (2017-01-01)
A series of 6-(4-substituted phenyl)-9-(tetrahydropyran-2-yl) purines 3-9, 6-(4-substituted phenyl) purines 10-16, 9-((4-substituted phenyl) sulfonyl)-6-(4-substituted phenyl) purines 17-32 were prepared and screened initially for their in vitro anticancer activity against selected human cancer cells (liver Huh7, colon HCT116, breast MCF7). 6-(4-Phenoxyphenyl) purine analogues 9, 16, 30-32, had potent cytotoxic activities. The most active purine derivatives 5-9, 14, 16, 18, 28-32 were further screened for t...
Synthesis, anticancer activity, toxicity evaluation and molecular docking studies of novel phenylaminopyrimidine-(thio)urea hybrids as potential kinase inhibitors.
Ture, Asli; Kahraman, Deniz Cansen; Atalay, Rengül; Helvacioglu, Sinem; Charehsaz, Mohammad; KÜÇÜKGÜZEL, İLKAY (2019-02-01)
Thirty-two novel urea/thiourea compounds as potential kinase inhibitor were designed, synthesized and evaluated for their cytotoxic activity on breast (MCF7), colon (HCT116) and liver (Huh7) cancer cell lines. Compounds 10, 19 and 30 possessing anticancer activity with IC50 values of 0.9, 0.8 and 1.6 mu M respectively on Huh7 cells were selected for further studies. These hit compounds were tested against liver carcinoma panel. Real time cell electronic sensing assay was used to evaluate the effects of the ...
Synthesis and cellular bioactivities of novel isoxazole derivatives incorporating an arylpiperazine moiety as anticancer agents.
ÇALIŞKAN, BURCU; Nalbat, Esra; Ibis, Kubra; Guzelcan, Ece Akhan; Atalay, Rengül; BANOĞLU, ERDEN (2018-12-01)
In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 51-o showed the most potent cytotoxicity on all cell lines with IC50 values in the range of 0.3-3.7 mu M. To explore the mechanistic aspects fundamental to the observed activity, further biological studies with 5m and 5o i...
Capture of rare circulating tumor cells from blood on bio-activated oxide surface inside microfluidic channels
Ateş, Hatice Ceren; Külah, Haluk; Özgür, Ebru; Department of Micro and Nanotechnology (2018)
Isolation and characterization of circulating tumor cells (CTCs) have important clinical significance in terms of prognosis and early detection of response to treatment. Moreover, downstream characterization of CTCs may help better patient stratification and therapy guidance. However, CTCs are extremely rare (~10 CTCs/1010 peripheral blood cells) and highly sensitive, and specific technology is required for their isolation. Rapidly developing microfluidic technologies offer variety of advantages in rare cel...
Novel triazolothiadiazines act as potent anticancer agents in liver cancer cells through Akt and ASK-1 proteins
Aytac, Peri S.; Durmaz, Irem; Houston, Douglas R.; Atalay, Rengül; TOZKOPARAN KÖPRÜCÜ, BİRSEN (2016-02-15)
Newly designed triazolothiadiazines incorporating with structural motifs of nonsteroidal analgesic anti-inflammatory drugs were synthesized and screened for their bioactivity against epithelial cancer cells. Compounds with bioactivities less then similar to 5 mu M (IC50) were further analyzed and showed to induce apoptotic cell death and SubG(1) cell cycle arrest in liver cancer cells. Among this group, two compounds (1g and 1h) were then studied to identify the mechanism of action. These molecules triggere...
Citation Formats
M. TUNÇBİLEK, A. Kucukdumlu, E. B. Guven, D. Altiparmak, and R. Atalay, “Synthesis of novel 6-substituted amino-9-(beta-D-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells,” BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, pp. 235–239, 2018, Accessed: 00, 2020. [Online]. Available: