Advances in structural identification of some thieno[2,3-d]pyrimidine scaffolds as antitumor molecules: Synthetic approaches and control programmed cancer cell death potential

• Published in: Bioorganic chemistry 2025-01, Vol.154, p.107985, Article 107985
• Main Authors: Mghwary, Aml E-S., Hassan, Rasha A., Halim, Peter A., Abdelhameid, Mohammed K.
• Format: Article
• Language: English
• Subjects: Anticancer activity; Apoptosis; Necroptosis; Structure-activity relationship; Synthetic approaches; Thieno[2,3-d]pyrimidine
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107985

[Display omitted] •Extra hydrophobic moiety at C-5,6 of the thienopyrimidine scaffold potentiates the activity.•Necroptotic cell death can led to development of effective cytotoxic compounds.•Phenyl urea fragment at C-2 of the thienopyrimidine ring is favorable for the activity.•The nature and position of the substituents greatly impact the activity.•Thieno[2,3-d]pyrimidines exert cytotoxic activity through affecting various pathways. Thieno[2,3-d]pyrimidine fragment is not only bioistostere to quinazoline ring but also to purines which exist in nucleic acids responsible for several key biological processes of the living cells, thus it is of a great interest for many researchers. Thieno[2,3-d]pyrimidine ring has become an important scaffold for different compounds with versatile pharmacological activities including anticancer. These compounds exert their anticancer activity through variant mechanisms of action; one of these is the induction of different programmed cell death types as apoptosis and necroptosis which is an effective approach for cancer treatment. This review highlights the different synthetic approaches of recent thieno[2,3-d]pyrimidine analogs along with their anticancer significance through induction of apoptotic or necroptotic cell death with illustration of the structure–activity relationship (SAR).