Design, synthesis and evaluation of PD176252 analogues for ameliorating cisplatin-induced nephrotoxicity. Issue 5 (11th April 2019)

• Record Type: Journal Article
• Authors: Yao, Sen; Wei, Biao; Yu, Mingjun; Meng, Xiaoming; He, Meng; Yao, Risheng
• Is Part Of: MedChemComm. Volume 10:Issue 5(2019)
• Page Start: 757
• Page End: 763
• Publication Date: 2019-04-11
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c8md00632f
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : The PD analogues were good at ameliorating cisplatin-induced renal toxicity and were not toxic to normal cells. Abstract : Cisplatin is a clinical chemotherapy drug for cancers; however, its remarkably high kidney toxicity and other toxicities pose a danger to patients. As the small molecule inhibitor of GRPR, PD176252 can inhibit the growth and proliferation of various cancer cells, but the characteristics of high toxicity and poor water solubility has limited its use as a drug. When we studied PD176252 for the reduction of toxicity of cisplatin, we modified its structure to synthesize 16 analogues. Surprisingly, the analogues showed reduced cisplatin-induced renal toxicity, and unlike PD176252, the analogues5d and5m were almost non-toxic to the normal HK2 cells. Furthermore, the analogue5d and PD176252 were subjected to cisplatin-induced inflammatory response in vitro . The results showed that5d was able to better prevent this condition by effectively inhibiting its inflammatory response. Thus, this study will help in clinically reducing the side effects of cisplatin.