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  • Title: Diorganotin(IV) derivatives of substituted N-hydroxybenzamides with selective cytotoxicity in vitro and potent antitumor activity in vivo.
    Author: Li YL, Wang ZW, Guo P, Tang L, Ge R, Ban SR, Chai QY, Niu L, Li QS.
    Journal: J Inorg Biochem; 2014 Apr; 133():1-7. PubMed ID: 24413257.
    Abstract:
    Four diorganotin(IV) derivatives, dibutylbis[4-chloro-N-(hydroxy-<κ>O)benzamidato-<κ>O]tin(IV) (DBDCT), dibutylbis[2,6-difluoro-N-(hydroxy-<κ>O)benzamidato-<κ>O]tin(IV) (DBDFT), bis[2,4-difluoro-N-(hydroxy-<κ>O)benzamidato-<κ>O]diphenyltin(IV) (DPDFT), and bis[2,4-dichloro-N-(hydroxy-<κ>O)benzamidato-<κ>O]diphenyltin(IV) (DPDCT), were compared for their antitumor activity in vitro and in vivo along with their cytotoxic selectivity against human normal cells and cancer cells. The in vitro cytotoxic activities against seven human cancer cell lines including Hep G2, SHSY5Y, HEC-1-B, EC, T24, HeLa and A549 along with human liver HL-7702, a human normal hepatocytes cell, were observed by the MTT assay. The cytotoxic selectivity of the four compounds was compared by using HL-7702 and Hep G2. The in vivo antitumor tests towards the sarcoma carcinoma S180 and hepatocellular carcinoma H22 on mice were carried out via injection intraperitoneally with cisplatin as the positive contrast drug. The results showed that, among the four compounds, DBDCT displayed the strongest cytotoxicity against the seven cancer cell lines. DPDCT had the highest antitumor activity in vivo. However, both of them had no cytotoxic selectivity against the human hepatocellular carcinoma HepG2 cells and normal liver HL-7702 cells. DPDFT had the most significant cytotoxic selectivity against HepG2 and displayed significantly antitumor activity in vitro and in vivo. In conclusion, DPDFT could act as a promising lead compound for the further structure optimization owing to its relatively low toxicity to human normal cell and potent antitumor activity against cancer cells.
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