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BACKGROUND A combination of paclitaxel with antineoplastic agents or paclitaxel alone was used clinically for the treatment of metastatic breast cancer. However, paclitaxel has poor water solubility and limited effect on some metastatic breast cancers. Hence, novel paclitaxel derivatives are in demand. In addition, the inducible nitric oxide synthase inhibitor, and aminoguanidine has a synergistic antitumor effect with chemotherapeutics. OBJECTIVE This study aims to design and synthesize the paclitaxel-aminoguanidine conjugates. Upon cellular internalization, the novel paclitaxel-aminoguanidine conjugates could release paclitaxel and aminoguanidine with the aid of esterase and weak acids in cancer cells. MATERIALS AND METHODS Paclitaxel-aminoguanidine conjugates were synthesized using click chemistry. The biological activity of paclitaxel-aminoguanidine conjugates was evaluated by MTT assay, determination of nitric oxide, analysis of apoptosis and cell cycle, and wound healing assay. RESULTS AND DISCUSSION Here, a novel paclitaxel-aminoguanidine conjugate was synthesized using click chemistry. Compared with paclitaxel, the water solubility of paclitaxel-aminoguanidine conjugates increased obviously. Upon cellular internalization, the novel paclitaxel-aminoguanidine conjugates released paclitaxel and aminoguanidine to synergistically inhibit the proliferation and metastasis of breast cancer cells with the aid of esterase and weak acids in cancer cells. The results of the MTT assay showed that compared with paclitaxel or the mixture of paclitaxel and aminoguanidine, the cytotoxicity of compound 4 against 4T1 cells was enhanced. As for apoptosis induced by these compounds, the paclitaxel-aminoguanidine conjugates also had a stronger ability to induce apoptosis than paclitaxel or the mixture of paclitaxel and aminoguanidine. The results of the scratch test showed that the anti-metastatic effect of the conjugate was the strongest among these tested compounds. CONCLUSION These findings indicate that paclitaxel-aminoguanidine conjugate is a promising anticancer agent worthy of further study.