Abstract: Sulfonamide drugs have emerged as a hotspot in drug development due to their diverse bioactivities （anticancer, bacteriostatic, anti-inflammatory, and others）. Our previous study identified the gastrin-releasing peptide receptor （GRPR） inhibitor RH-1402 as a renal protectant against cisplatin-induced nephrotoxicity through anti-inflammatory mechanisms. Based on these findings, five novel sulfonamide-containing derivatives （3a-3e） were designed and synthesized through structural modification, followed by a systematic evaluation of their biological profiles. The results revealed that compounds 3a and 3b displayed significant antiproliferative activity against human K562 chronic myeloid leukemia cells \[IC50=（10.5±1.1） μmol/L and （12.8±2.0） μmol/L, respectively\]. Notably, derivative 3d demonstrated remarkable dual functionality: it exhibited potent bacteriostatic activity againstEnterococcus（MIC=62.5 μg/mL） and significantly mitigated cisplatin-induced renal injury. In thein vitromodels, 3d improved the cell viability of murine renal tubular epithelial cells （mRTEC） from 50% to 68.1%±3.2%, while concurrently downregulating the expression of the renal injury marker KIM-1 and key inflammatory cytokines （TNF-α, IL-6, MCP-1）. This study demonstrated that the introduction of the sulfonamide structure successfully expanded the biological activity spectrum of RH-1402 derivatives. Among them, the multifunctional compound 3d exhibited anticancer, bacteriostatic, and nephroprotective properties, making it a promising candidate for further drug development.

Key words: sulfonamide derivatives, gastrin-releasing peptide receptor, RH-1402, structure-activity relationship, bacteriostatic activity