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: Manal Kandeel, Mohammed Kamal Abdelhameid, Kamal Eman, Madlen Berty Labib
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 61 Issue 6 Pg. 637-47 ( 2013) ISSN: 1347-5223 [Electronic] Japan
• PMID: 23538397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Pyrimidines
• thienopyrimidine
• Doxorubicin
• DNA

Topics

• Antineoplastic Agents (chemical synthesis, therapeutic use, toxicity)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• DNA (chemistry)
• Doxorubicin (therapeutic use, toxicity)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Hydrogen Bonding
• MCF-7 Cells
• Pyrimidines (chemistry, therapeutic use, toxicity)
• Structure-Activity Relationship