Abstract:The efficacy of drugs against cancer in clinical settings may be limited due to pharmacokinetic issues, side effects and the emergence of drug resistance. However, a class of anticancer drugs known as naphthalimides have proven to be very effective. These derivatives have demonstrated to be effective in treating different types of cancers and exhibit strong DNA binding affinity. The anticancer properties of the naphthalimide derivatives allow them to target a number of cancer cell lines. Researchers have investigated the anticancer activity of numerous naphthalimide derivatives, such as heterocyclic fused, non-fused substituted, metal-substituted and carboxamide derivatives. Surprisingly, some derivatives demonstrate greater activity than the reference norms, such as cisplatin, amonafide, mitonafide and others and are selective against many cell lines. The primary objective of this research is to comprehend the effects of various substitution patterns on the structure-activity relationship (SAR) of these derivatives and the instances in which they enhance or reduce this biological activity.

01 Jan 2024·Technology in Cancer Research & Treatment

Research Progress on Structure-Activity Relationship of 1,8-Naphthalimide DNA Chimeras Against Tumor

Review

Author: Yu, Meng-bin ; Han, Li-li ; Chen, Gao-yun ; Wu, Hong-yi ; Xu, Xiang-xiang ; Qi, Xiu-li ; Zhang, Hai-yang

The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.

31 Dec 2023·Journal of Enzyme Inhibition and Medicinal Chemistry

Carboranyl-1,8-naphthalimide intercalators induce lysosomal membrane permeabilization and ferroptosis in cancer cell lines

Article

Author: Wyszko, Eliza ; Olejniczak, Agnieszka B. ; Rypniewski, Wojciech ; Kowalczyk, Aleksandra ; Gurda-Woźna, Dorota ; Orlicka-Płocka, Marta ; Biniek-Antosiak, Katarzyna ; Stączek, Paweł ; Denel-Bobrowska, Marta ; Rykowski, Sebastian ; Fedoruk-Wyszomirska, Agnieszka

The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding properties were investigated using circular dichroism, UV-vis spectroscopy, and thermal denaturation. Results showed that conjugates 34-37 interacted very strongly with ct-DNA (ΔT_m = 10.00-13.00 °C), indicating their ability to intercalate with DNA, but did not inhibit the activity of topoisomerase II. The conjugates inhibited the cell growth of the HepG2 cancer cell line in vitro. The same compounds caused the G2M phase arrest. Cell lines treated with these conjugates showed an increase in reactive oxygen species, glutathione, and Fe²⁺ levels, lipid peroxidation, and mitochondrial membrane potential relative to controls, indicating the involvement of ferroptosis. Furthermore, these conjugates caused lysosomal membrane permeabilization in HepG2 cells but not in MRC-5 cells.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 2	-	Abbott Laboratories	-
Neoplasms	Phase 2	ES	-	-

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