TY - JOUR
T1 - Development of novel naphthalimide derivatives and their evaluation as potential melanoma therapeutics
AU - Sk, Ugir Hossain
AU - Prakasha Gowda, A. S.
AU - Crampsie, Melissa A.
AU - Yun, Jong K.
AU - Spratt, Thomas E.
AU - Amin, Shantu
AU - Sharma, Arun K.
N1 - Funding Information:
This study was supported by the Elsa U. Pardee Foundation Grant (A.K. Sharma). The authors thank the Flow Cytometry and Solution Phase NMR Facility (Dr. Jyh-Ming Lin) at Core Research Facilities of the Pennsylvania State University, College of Medicine, for recording of NMR spectra. The melanoma cell lines were graciously provided by Dr. Gavin Robertson, Penn State College of Medicine, Hershey, PA.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ejmech.2011.04.058
DO - 10.1016/j.ejmech.2011.04.058
M3 - Article
C2 - 21609852
AN - SCOPUS:79958272593
SN - 0223-5234
VL - 46
SP - 3331
EP - 3338
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 8
ER -
