Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1350, 2026 (SCI-Expanded, Scopus)
Pyrazole and pyrazoline derivatives are heterocyclic compounds with notable anticancer activity, and some are already in clinical use. Although many such compounds have been reported to induce apoptosis through G2/M arrest, studies on pyrazole/pyrazoline-benzenesulfonamides in both malignant and non-malignant cells from the same tissue are limited. In this work, we designed and synthesized 95 pyrazoline-benzenesulfonamides having 4-[5-Aryl-3-(phenyl/p-tolyl/4-methoxyphenyl/4-fluorophenyl/thiophene-3-yl)-4,5-dihydro-1H-pyrazole-1-yl] benzenesulfonamides (1–95) chemical structure and evaluated their cytotoxicity in oral cancer cells (Ca9–22, HSC-2) and normal oral cells (HGF, HPLF). Among them, three compounds (56, 63, and 94) exhibited strong tumor selectivity. These compounds induced G1 arrest without subG1 accumulation or apoptosis, suggesting a non-apoptotic mechanism. QSAR analysis showed that tumor-specificity correlated with descriptors reflecting molecular topology, charge distribution, and size. Tox21 database screening indicated possible involvement of multiple signaling pathways, including ERRPGC, AhR, TSHR, VDR, and PPARδ. Notably, estrogen-related receptor activation with PGC agonist may contribute to tumor selectivity, treatment resistance, and malignancy. Overall, our findings highlight the tumor-specific potential of pyrazoline-benzenesulfonamides and the importance of predicting optimal chemical structures through molecular descriptors to guide the design compounds in future studies.