PMID- 28458134
OWN - NLM
STAT- MEDLINE
DCOM- 20170928
LR  - 20171116
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 135
DP  - 2017 Jul 28
TI  - Design, synthesis, and identification of a novel napthalamide-isoselenocyanate 
      compound NISC-6 as a dual Topoisomerase-IIalpha and Akt pathway inhibitor, and 
      evaluation of its anti-melanoma activity.
PG  - 282-295
LID - S0223-5234(17)30318-5 [pii]
LID - 10.1016/j.ejmech.2017.04.052 [doi]
AB  - Synthesis and anti-melanoma activity of novel naphthalimide isoselenocyanate 
      (NISC) and naphthalimide selenourea (NSU) analogs are described. The novel agents 
      were screened for growth inhibition of different human melanoma cell lines 
      including those having BRAF(V600E) mutation (UACC903, 1205Lu, and A375M) and 
      BRAF(WT) (CHL-1). In general, the NISC analogs (4a-d) were more effective in 
      inhibiting the cell viability than the NSU analogs (7a-b). Overall, NISC-6 (4d), 
      having a six-carbon alkyl chain, was identified as the most cytotoxic compound in 
      both BRAF(V600E) mutated and BRAF(WT) cells. NISC-6 docked strongly into the 
      binding sites of Akt1 and human topoisomerase IIalpha (Topo-IIalpha), and the docking 
      results were supported by experimental findings showing NISC-6 to inhibit of both 
      Akt pathway and Topo-IIalpha activity in a dose dependent manner. Furthermore, NISC-6 
      effectively induced apoptosis in human melanoma cells, inhibited tumor growth by 
       approximately 69% in a melanoma mouse xenograft model, and showed excellent compliance with 
      the Lipinski' rule of five, suggesting both its efficacy and drug-like behavior 
      under physiological conditions.
CI  - Copyright (c) 2017 Elsevier Masson SAS. All rights reserved.
FAU - Karelia, Deepkamal N
AU  - Karelia DN
AD  - Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College 
      of Medicine, 500 University Drive, Hershey, PA 17033, USA.
FAU - Sk, Ugir Hossain
AU  - Sk UH
AD  - CSIR-Institute of Himalayan Bioresource Technology, Palampur, HP, India.
FAU - Singh, Parvesh
AU  - Singh P
AD  - School of Chemistry and Physics, University of Kwa-Zulu Natal (UKZN), Westville 
      Campus, Durban 4000, South Africa.
FAU - Gowda, A S Prakasha
AU  - Gowda ASP
AD  - Department of Biochemistry and Molecular Biology, Penn State College of Medicine, 
      500 University Drive, Hershey, PA 17033, USA.
FAU - Pandey, Manoj K
AU  - Pandey MK
AD  - Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College 
      of Medicine, 500 University Drive, Hershey, PA 17033, USA.
FAU - Ramisetti, Srinivasa R
AU  - Ramisetti SR
AD  - Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College 
      of Medicine, 500 University Drive, Hershey, PA 17033, USA.
FAU - Amin, Shantu
AU  - Amin S
AD  - Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College 
      of Medicine, 500 University Drive, Hershey, PA 17033, USA.
FAU - Sharma, Arun K
AU  - Sharma AK
AD  - Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College 
      of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: 
      aks14@psu.edu.
LA  - eng
PT  - Journal Article
DEP - 20170421
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NISC-6)
RN  - 0 (Naphthalenes)
RN  - 0 (Nitriles)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
SB  - IM
MH  - Antigens, Neoplasm/metabolism
MH  - Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - DNA Topoisomerases, Type II/metabolism
MH  - DNA-Binding Proteins/*antagonists & inhibitors/metabolism
MH  - Dose-Response Relationship, Drug
MH  - *Drug Design
MH  - Drug Screening Assays, Antitumor
MH  - Enzyme Inhibitors/chemical synthesis/chemistry/*pharmacology
MH  - Humans
MH  - Melanoma/*drug therapy/pathology
MH  - Molecular Structure
MH  - Naphthalenes/chemical synthesis/chemistry/*pharmacology
MH  - Nitriles/chemical synthesis/chemistry/*pharmacology
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Anti-Tumor
OT  - Apoptosis
OT  - Isoselenocyanate
OT  - Melanoma
OT  - Naphthalimide
OT  - Selenourea
EDAT- 2017/05/02 06:00
MHDA- 2017/09/29 06:00
CRDT- 2017/05/02 06:00
PHST- 2016/12/09 00:00 [received]
PHST- 2017/04/11 00:00 [revised]
PHST- 2017/04/20 00:00 [accepted]
PHST- 2017/05/02 06:00 [pubmed]
PHST- 2017/09/29 06:00 [medline]
PHST- 2017/05/02 06:00 [entrez]
AID - S0223-5234(17)30318-5 [pii]
AID - 10.1016/j.ejmech.2017.04.052 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2017 Jul 28;135:282-295. doi: 10.1016/j.ejmech.2017.04.052. Epub 
      2017 Apr 21.