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oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/118342026-10-18T21:13:17Zopenairedrivercom_ebyu_10000col_ebyu_10001

Synthesis and cytotoxicity of novel 6,8,9-trisubstituted purine analogs against liver cancer cellsFatih Polat, M.Durmaz Şahin, IremKul, PınarCetin Atalay, RengulTuncbilek, MeralADMETCytotoxic activityHepatocellular carcinomaPurine analogsSynthesisAntineoplastic AgentsCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansLiver NeoplasmsMolecular StructurePurinesStructure-Activity Relationship4 fluoro phenyl4 methoxy phenyl4 trifluoromethyl phenyl4,6 dichloro 5 nitropyrimidine4,6 dichloropyrimidin 5 amine6 (substituted phenyl piperazine) 8 (4 substituted phenyl) 9 cyclopentyl purine derivativeantineoplastic agentcladribinefludarabinefluorouracilphenyl grouppurine derivativesulforhodamine Bunclassified drugantineoplastic activityA series of novel 6-(substituted phenyl piperazine)-8-(4-substituted phenyl)-9-cyclopentyl purines, 10–51, were synthesized by a four-step synthesis, achieving an overall yield of about 43 %. The reaction conditions were effectively optimized, and the final products were obtained with high purity and yield in all synthesis steps. The synthesized nucleobases were evaluated for their in vitro cytotoxic activities on selected human cancer cell lines (HUH7 (liver), HCT116 (colon), and MCF7 (breast)) using the Sulforhodamine B (SRB) assay. Among these analogs, compounds bearing 4-trifluoromethyl phenyl (19, 20 and 21), 4-methoxy phenyl (27) and 4-fluoro phenyl (34) substitutions at C-8 of purine were the most potent, and they were also analyzed in drug-resistance and drug-sensitive hepatocellular cancer cell (HCC) panels. Compound 19 displayed remarkable anticancer activities (IC50 = 2.9–9.3 μM) against Huh7, FOCUS, SNU475, SNU182, HepG2, and Hep3B cells compared to the positive control, Fludarabine. Additionally, the pharmacological properties and toxicity profiles of the molecules were investigated computationally by the Swiss-ADME and Pro-Tox II online tools, respectively. Results showed that our compounds have favorable physicochemical characteristics for oral bioavailability and do not reveal any toxicity endpoints such as carcinogenicity, immunotoxicity, mutagenicity, or cytotoxicity. © 2024 Elsevier LtdElsevier Ltd2024Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/11834https://doi.org/10.1016/j.bmcl.2024.1297750960-894XenBioorganic and Medicinal Chemistry Lettersinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/11834