title: Antitumor activity of novel pyrrolo[2,3-d]pyrimidin-4-ones.
abstract: Pyrrolo[2,3-d]pyrimidine is known to have a broad spectrum of biological activities, including antitumor activity. The cytotoxic properties of six novel pyrrolo[2,3-d]pyrimidin-4-ones in vitro were investigated on four different human cancer cell lines. Meanwhile, the role of apoptosis was explored. Malignant cells were cultured in RPMI medium and incubated with different concentrations. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using DAPI (4'-6-diamidino-2-phenylindole) and propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). We have identified new analogs as a novel class of antiproliferative agents by a cell-based screening method. All compounds inhibited the growth of malignant cells in a dose-dependent manner. The IC₅₀ of compounds 4 and 5 as the two most potent analogs was determined as 122.4 and 106.7 μM in HeLa cells, respectively. Compounds 4 and 5 induced a sub-G1 peak in the flow-cytometry histogram of treated cells, compared to control, indicating that apoptotic cell death is involved in compound 4- and 5-induced toxicity. In conclusion, compounds 4 and 5 exert cytotoxic effects in different cancer cell lines in which apoptosis plays an important role. Thus, compounds 4 and 5 could be considered as potential chemotherapeutic agents.
authors.affiliation: Department of Chemistry, Payame Noor University (PNU), Mashhad, Iran.
authors.forename: Hoda
authors.initials: H
authors.lastname: Atapour-Mashhad
authors.forename: Zahra
authors.initials: Z
authors.lastname: Tayarani-Najaran
authors.forename: Abolghasem
authors.initials: A
authors.lastname: Davoodnia
authors.forename: Raheleh
authors.initials: R
authors.lastname: Moloudi
authors.forename: Seyed Hadi
authors.initials: SH
authors.lastname: Mousavi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D011758:Pyrroles; C527741:pyrrolopyrimidine