Development of novel naphthalimide derivatives and their evaluation as potential melanoma therapeutics.

Abstract

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.

• Authors: Ugir Hossain Sk, A S Prakasha Gowda, Melissa A Crampsie, Jong K Yun, Thomas E Spratt, Shantu Amin, Arun K Sharma
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 46 Issue 8 Pg. 3331-8 (Aug 2011) ISSN: 1768-3254 [Electronic] France
• PMID: 21609852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Chemical References

• Annexin A5
• Antineoplastic Agents
• Isothiocyanates
• Naphthalimides
• isothiocyanic acid
• Thiourea

Topics

• Animals
• Annexin A5 (analysis)
• Antineoplastic Agents (chemical synthesis, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Flow Cytometry
• Humans
• Hydrophobic and Hydrophilic Interactions
• Injections, Intraperitoneal
• Isothiocyanates (chemistry)
• Melanoma (drug therapy, pathology)
• Mice
• Mice, Nude
• Naphthalimides (chemical synthesis, pharmacology, therapeutic use)
• Neoplasm Transplantation
• Skin Neoplasms (drug therapy, pathology)
• Structure-Activity Relationship
• Thiourea (chemistry)