1,3,5-Triazine-benzenesulfonamide hybrids: are they cytotoxic?

Abstract

In contemporary pharmaceutical research, cytotoxicity assays constitute an indispensable tool in the systematic evaluation of drug candidates. The identification of cytotoxic effects at early stages of development is critical, as it allows for the elimination of compounds with unfavourable toxicological properties prior to their advancement into preclinical and clinical testing. Despite the essential role of cytotoxicity studies, the relationship between chemical structure and cytotoxic outcome remains insufficiently defined for many classes of compounds. In this context, 1,3,5-triazine derivatives have emerged as a particularly promising scaffold due to their broad spectrum of biological activities, with notable emphasis on anticancer potential. However, the absence of a comprehensive structure–cytotoxicity correlation highlights the need for systematic evaluation and consolidation of findings. In this review, we provide an overview of triazine-benzenesulfonamide hybrid molecules, including their synthesis and purification procedures, as well as their biological activity and cytotoxicity. The novel strategies in new candidate drug development and structure modifications related to their effects on investigated protein and/or non-protein targets, as well as various cell lines, are included to demonstrate a relationship between structure and antiproliferative activity, as well as cytotoxicity. Moreover, the literature reveals substantial variability in the methods used to assess antiproliferative and cytotoxic activity, which hinders comparisons and the interpretation of structure–activity relationships. Adoption of a standardized framework—particularly consistent reporting of IC₅₀ values—would improve reproducibility, facilitate meaningful cross-study comparisons, and provide a stronger foundation for linking molecular design with biological response. Ultimately, such standardisation may advance drug discovery and support the rational modification of chemical structures to enhance therapeutic potential.