Galactose conjugated platinum(II) complex targeting the Warburg effect for treatment of non-small cell lung cancer and colon cancer

European Journal of Medicinal Chemistry
Meng WuQingzhi Gao

Abstract

Malignant neoplasms exhibit a higher rate of glycolysis than normal cells; this is known as the Warburg effect. To target it, a galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-chloromalonato-platinum(II) complex (Gal-Pt) was designed, synthesized, and evaluated in five human cancer cell lines and against two different xenograft tumour models. Gal-Pt exhibits much higher aqueous solubility (over 25 times) and improved cytotoxicity than oxaliplatin, especially in human colon (HT29) and lung (H460) cancer cell lines. The safety profile of Gal-Pt was investigated in vivo by exploring the maximum tolerated dose (MTD) and animal mortality rate. The ratios of the animal lethal dosage values to the cytotoxicity in HT29 (LD50/IC50) showed that Gal-Pt was associated with an increased therapeutic index by over 30-fold compared to cisplatin and oxaliplatin. We evaluated in vivo antitumor activity by single agent intravenous treatment comparison studies of Gal-Pt (50 mg/kg as 65% MTD) and cisplatin (3 mg/kg, as 80% MTD) in a H460 lung cancer xenograft model, and with oxaliplatin (7 mg/kg, as 90% MTD) in a HT29 colon cancer xenograft model. The results show that Gal-Pt was more efficacious against H460 than cisplatin, and had supe...Continue Reading

References

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Citations

Apr 2, 2016·Biochemical and Biophysical Research Communications·Hu XuQingzhi Gao
Oct 26, 2016·Biochemical and Biophysical Research Communications·Xiangyin LiuQingzhi Gao
Jan 4, 2017·MedChemComm·C GranchiF Minutolo
May 10, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Alfonso AnnunziataFrancesco Ruffo
Nov 14, 2019·Future Medicinal Chemistry·Fang ChenHualiang Huang
Apr 4, 2020·Journal of Drug Targeting·Changmei ZhangMingming Lian
Aug 1, 2020·ChemMedChem·Giulia BononiFilippo Minutolo
Jul 28, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aoife M McKeonDarren M Griffith
Aug 20, 2019·European Journal of Medicinal Chemistry·Fang Chen, Gangliang Huang
Feb 23, 2020·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Sabrina DallavalleRoberta Fruttero
Jul 3, 2021·International Journal of Molecular Sciences·Aldona Kasprzak
Mar 30, 2017·Biochemistry·Xianfeng ZengHang Yin

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