Development of novel naphthalimide derivatives and their evaluation as potential melanoma therapeutics
详细信息 查看全文
- 作者：Ugir Hossain Sk ; A.S. Prakasha Gowda ; Melissa A. Crampsie ; Jong K. Yun ; Thomas E. Spratt ; Shantu Amin ; Arun K. Sharma
- 关键词：Naphthalimide ; Isothiocyanate ; Thiourea ; Melanoma ; anti-Tumor ; Apoptosis
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：August 2011
- 年：2011
- 卷：46
- 期：8
- 页码：3331-3338
- 全文大小：971 K
文摘
Synthesis and anti-melanoma activity of various naphthalimide analogs, rationally modified by introducing isothiocyanate (ITC) and thiourea (TU) functionalities, found in well-known anti-cancer agents, is described. The structure–activity relationship comparison of the novel agents in inhibiting cancer cell growth was evaluated in various melanoma cell lines. Both ITC and TU analogs effectively inhibited cell viability and induced apoptosis in various human melanoma cells. Nitro substitution and increase in alkyl chain length, in general, enhanced the apoptotic activity of ITC derivatives. All the new compounds were well tolerated when injected intraperitoneal (i.p.) in mice at effective doses at which both the ITC and TU derivatives inhibited melanoma tumor growth in mice following i.p. xenograft. The nitro substituted naphthalimide–ITC derivative 3d was found to be the most effective in inducing apoptosis, and in inhibiting melanoma cell and tumor growth.