# Structural and Functional Aspects of DHPM-Thiones and Their Derivatives: A Critical Review of Pharmaceutical Potential

## TL;DR

This review explores the pharmaceutical potential of DHPM-thiones and their derivatives, highlighting their promising roles in drug development for viral and cancer treatments.

## Contribution

The paper systematically reviews recent innovations and structure-activity relationships of DHPM-thiones from 2020–2025, emphasizing their translational potential.

## Key findings

- Structural modifications like N-methylation and C4/C5 substitutions enhance biological potency against viral proteases and cancer cells.
- Compounds such as LaSOM 65 and Ru(II)–Biginelli hybrids show strong inhibitory effects and multitarget activity.
- The field is projected to advance to phase I trials by 2030, indicating significant translational potential.

## Abstract

Background: Amidst escalating global challenges such as antimicrobial resistance and post-COVID therapeutic gaps, dihydropyrimidines (DHPs) and their thione derivatives have emerged as a highly promising scaffold for drug development. This systematic review aims to consolidate recent advancements (2020–2025) and evaluate the synthetic innovation, structure–activity relationships (SAR), and preclinical potential of these compounds. Methods: A systematic review was conducted according to PRISMA guidelines, searching multiple electronic databases (Scopus, PubMed, Web of Science). Sixty original studies from 2020 to 2025 meeting predefined inclusion criteria were selected for data extraction and qualitative synthesis. Results: The analysis reveals a surge in publications (over 300% since 2020). Key structural modifications, such as N-methylation to improve bioavailability and specific substitutions at C4/C5 positions, significantly enhance biological potency, yielding strong inhibitory effects against viral proteases and cancer cell lines. Notable compounds include the apoptosis inducer LaSOM 65 and multitarget Ru(II)–Biginelli hybrids. Conclusions: This review affirms the timeliness and translational potential of the DHP scaffold. The field shows bright prospects for advancing to phase I trials by 2030, urging intensified exploration to unlock novel pharmaceuticals from this versatile chemotype.