Design, synthesis, and antitumor evaluation of novel naphthalimide derivatives
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In order to research the structure–activity relationships of novel naphthalimide derivatives bearing disulfide bond toward antitumor activity, we prepared a series of those and their in vitro antiproliferative activities were screened against human cancer cell lines A549, Hela, SMMC-7721, and normal cell lines L929 by CCK-8 assay. After testing, most of synthesized compounds 5a-i, 6a-i showed better antitumor activity than the positive control 5-fluorouracil. Compounds 5b, 5f, and 5i showed excellent antitumor activity against Hela cells with IC50 values of 3.64, 3.67, and 3.57 µM, respectively. Compounds 5a, 5b, and 5i exhibited good biological activity to A549 cells with IC50 values of 5.25, 6.20, and 5.50 respectively. Compared with 5-fluorouracil, all of synthesied compounds showed low cytotoxic effects on normal human cell line L929.
Keyword1,8-Naphthalimide Synthesis Disulfides; Antiproliferative activities
We are grateful to the Tianjin Municipal Natural Science Foundation (18JCYBJC94900) and Training Project of Innovation Team of Colleges and Universities in Tianjin (TD13-5020) for financial support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Banerjee S, Veale EB, Phelan CM, Murphy SA, Tocci GM, Gillespie LJ, Frimannsson DO, Kelly JM, Gunnlaugsson T (2013) Recent advances in the development of 1,8-naphthalimide based DNA targeting binders, anticancer and fluorescent cellular imaging agents. Chem Soc Rev 42:1601–1618PubMedCrossRefGoogle Scholar
- Cesarini S, Spallarossa A, Ranise A, Schenone S, Bruno O, Colla PL, Casula L, Collu G, Sanna G, Loddo R (2008) Parallel one-pot synthesis and structure–activity relationship study of symmetric formimidoester disulfides as a novel class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Bioorg Med Chem 16:6353–6363PubMedCrossRefGoogle Scholar
- El-Azab AS, Alanazi AM, Abdel-Aziz NI, Al-Suwaidan IA, El-Sayed MA, El-Sherbeny MA, Abdel-Aziz AA (2013) Synthesis, molecular modeling study, preliminary antibacterial, and antitumor evaluation of N-substituted naphthalimides and their structural analogue. Med Chem Res 22:2360–2375CrossRefGoogle Scholar
- Freitas RHCN, Cordeiro NM, Carvalho PR, Alves MA, Guedes IA, Valerio TS, Dardenne LE, Lima LM, BArreiro EJ, Fernandes PD, Fraga GAM (2018) Discovery of naphthyl-N- acylhydrazone p38α MAPK inhibitors with in vivo anti-inflammatory and anti-TNF-α activity. Chem Biol Drug Des 91:391–397PubMedCrossRefGoogle Scholar
- Ghane T, Nozaki D, Dianat A, Vladyka A, Gutierrez R, Chinta JP, Yitzchaik S, Calame M, Cuniberti G (2015) Interplay between Mechanical and Electronic Degrees of Freedom in π-stacked molecular junctions: from single molecules to mesoscopic nanoparticle networks. J Phys Chem C 119:6344–6355CrossRefGoogle Scholar
- Patil SR, Sarkate AP, Karnik KS, Arsondkar A, Patil V, Sangshetti JN, Bobade AS, Shinde DB (2019) A facile synthesis of substituted 2-(5-(benzylthio)-1,3,4-oxadiazol-2-yl) pyrazine using microwave irradiation and conventional method with antioxidant and anticancer activities. J Heterocycl Chem 56:859–866CrossRefGoogle Scholar
- Ponte-Sucre A, Bruhn H, Schirmeister T, Cecil A, Albert CR, Buechold C, Tischer M, Schlesinger S, Goebel T, Fuß A, Mathein D, Merget B, Sotriffer CA, Stich A, Krohne G, Engstler M, Bringmann G, Holzgrabe U (2014) Anti-trypanosomal activities and structural chemical properties of selected compound classes. Parasitol Res 114:501–512PubMedCrossRefGoogle Scholar
- Roldán-Peňa JM, Alejandre-Ramos D, López Ó, Maya I, Lagunes I, Padrón JM, Peňa-Altamira LE, Bartolini M, Monti B, Bolognesi ML, Fernández-Bolaňos JG (2017) New tacrine dimers with antioxidant linkers as dual drugs: Anti-Alzheimer’s and anti-proliferative agents. Eur J Med Chem 138:761–773PubMedCrossRefGoogle Scholar
- Shao J, Li YQ, Wang ZY, Xiao MM, Yin PH, Lu YH, Qian XH, Xu YF, Liu JW (2013) 7b, a novel naphthalimide derivative, exhibited anti-inflammatory effects via targeted-inhibiting TAK1 following down-regulation of ERK1/2- and p38 MAPK-mediated activation of NF-κB in LPS-stimulated RAW264.7 macrophages. Int Immunopharmacol 17:216–228PubMedCrossRefGoogle Scholar
- Turos E, Revell KD, Ramaraju P, Gergeres DA, Greenhalgh K, Young A, Sathyanarayan N, Dickey S, Lim D, Alhamadsheh MM, Reynolds K (2008) Unsymmetric aryl-alkyl disulfide growth inhibitors of methicillin-resistant Staphylococcus aureus and Bacillus anthracis. Bioorg Med Chem 16:6501–6508PubMedPubMedCentralCrossRefGoogle Scholar