title: Synthesis of some novel thieno[3,2-d]pyrimidines as potential cytotoxic small molecules against breast cancer.
abstract: A variety of novel thieno[3,2-d]pyrimidines with different decorating functional groups were synthesized as a part of a study aiming to enrich the arsenal of chemotherapeutic agents for the treatment of cancer. The design of synthetic molecules based on DNA-interchelating properties by hydrogen bond formation. The reported compounds herein are: 4-aminothienopyrimidine derivatives 4a, b and their 4-substituted phenylamino analogues 8a, b; 4-thienopyrimidin-4-ones 5a, b; N-alkyl thienopyrimidin-4-ones 6a-g; 4-chlorothienopyrimidines 7a, b and thienopyrimidoquinazolinones 9a, b which are the structural mimics of 8a, b. The synthesized molecules were evaluated for their in vitro cytotoxic activity against human breast cancer cell line (MCF-7). Biological screening revealed varying cytotoxic potencies of the tested molecules compared with Doxorubicin as a reference drug. The cytotoxicity results from the study suggested that the synthesized molecules are potential antitumor agents and compound 4a was the most potent with an IC 50 2.04 nm.
authors.affiliation: Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Manal
authors.initials: M
authors.lastname: Kandeel
authors.forename: Mohammed Kamal
authors.initials: MK
authors.lastname: Abdelhameid
authors.forename: Kamal
authors.initials: K
authors.lastname: Eman
authors.forename: Madlen Berty
authors.initials: MB
authors.lastname: Labib
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D004317:Doxorubicin / Q000627:therapeutic use / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D006860:Hydrogen Bonding; D061986:MCF-7 Cells; D011743:Pyrimidines / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; C476003:thienopyrimidine; D004317:Doxorubicin; D004247:DNA