Design, Synthesis, and Biological Evaluation of Substituted Naphthalene Imides and Diimides as Anticancer Agent

Abstract

Naphthalimmide (NI) and 1,4,5,8-naphthalentetracarboxylic diimide (NDI) derivatives were synthesized and evaluated for their antiproliferative activity. NDI derivatives 1-9 were more cytotoxic than the corresponding NI derivatives 10-18. The molecular mechanisms of 1 and 2 were investigated in comparison to mitonafide. They interacted with DNA, were not topoisomerase IIalpha poisons, triggered caspase activation, caused p53 protein accumulation, and down-regulated AKT survival. Furthermore, 1 and 2 caused a decrease of ERK1/2 and, unlike mitonafide, inhibited ERKs phosphorylation.

Design and Biological Evaluation of New Platinum(II) Complexes Bearing Ligands with DNA-Targeting Ability

“…13 First, synthesis of ligands a−c in which the naphthalimide intercalator is tethered with the corresponding spacer was easily achieved in high purity on large scale (Scheme 1). Ligands a and b were prepared following procedures reported in the literature, 24,25 while ligand c was obtained in 72% yield by reacting amine from ligand a and isonicotinoyl chloride in dry DMF.…”

“…25 Ligand b was synthesized following the procedure reported by Lichelli et al 24 General Procedure for Synthesis of trans-Platinum(II) Complexes 1a−c. To a solution of cis-[PtCl 2 (dma) 2 ] (0.20 g, 0.56 mmol) in a minimum amount of water was added the corresponding ligand a, b, or c (2.25 mmol), and the mixture was stirred at 95°C for 16 h. After cooling, the mixture was filtrated and the yellow solution was refluxed with hydrogen chloride (11.20 mmol) at 95°C for 1 (ligand a) or 16 h (ligands b and c) to obtain a solid, which was filtered, washed with water, and purified as indicated in each complex.…”

Evaluation of New Naphthalimides as Potential Anticancer Agents against Breast Cancer MCF-7, Pancreatic Cancer BxPC-3 and Colon Cancer HCT- 15 Cell Lines

“…Scheme 1 depicts the synthesis of naphthlimido alkylamine and alkyl alcohol products 1a-f in excellent yields. This was achieved by the reaction of naphthalic anhydride with corresponding diamines and amino alcohols in excess [14].…”

Design and Synthesis of Sulfamoyl Benzoic Acid Analogues with Subnanomolar Agonist Activity Specific to the LPA2 Receptor

“…N -Butylamino-1,8-naphthalimide ( 22 ) 14 was coupled with substituted sulfonyl chloride 23a – e using triethylamine in THF to furnish corresponding ester derivatives ( 12a – e ). Upon treatment of compound 12b – c with LiOH in THF–water (1:1) and compound 12d – e with K 2 CO 3 in DMF afforded the final acid derivatives 11a – b and 11c – d , respectively, in moderate to quantitative yield (Scheme 4).…”