# Anticancer Potential of Thieno[2,3-d]pyrimidine Derivatives in Oral Carcinoma Models

## TL;DR

This study explores new thienopyrimidine compounds that show promise in fighting oral cancer by stopping cancer cell growth and survival.

## Contribution

The study identifies thienopyrimidine derivatives as novel, selective anticancer agents with potential for targeted oral cancer therapy.

## Key findings

- Compounds 5 and 6 showed strong selective anticancer activity against oral cancer cells.
- The compounds caused S-phase arrest, apoptosis, and actin cytoskeleton disruption in cancer cells.
- In silico analysis confirmed favorable drug-like properties for the most active derivatives.

## Abstract

Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to aggressive progression, high recurrence, and limited selectivity of current treatments. In this study, a series of seven 4-amino-2-substituted tetrahydrobenzothieno[2,3-d]pyrimidines were evaluated for their cytotoxic, antiproliferative, and mechanistic effects against oral cancer cell lines with different metastatic potential (HSC-3 and SCC-9), alongside non-tumorigenic keratinocytes (HaCaTs). Several compounds demonstrated selective anticancer activity, with Compounds 5 and 6 showing the most favorable balance between potency and selectivity. Antiproliferative assays revealed effective inhibition of cancer cell growth, while clonogenic assays confirmed a pronounced reduction in long-term survival, particularly in highly metastatic HSC-3 cells. Mechanistic studies indicated that the anticancer effects are associated with S-phase cell cycle arrest, apoptosis induction, and profound disruption of the actin cytoskeleton. In silico ADME and drug-likeness analyses supported the lead-like properties of the most active derivatives. Overall, these findings identify thienopyrimidine derivatives as promising scaffolds for the development of targeted therapies against OSCC and warrant further optimization and in vivo evaluation.