Abstract
A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.
Highlights
DNA, the carrier of genetic information, is a prominent target in anticancer drug discovery programs
The designed chemical entities incorporating the DNA interacting bis-naphthalimides and naphthalene diimides moieties were subjected to DNA interaction analysis at molecular level using AutoDock software
The results revealed that the compounds exhibited excellent DNA intercalating property compared to the standard 3 (Table 1)
Summary
DNA, the carrier of genetic information, is a prominent target in anticancer drug discovery programs. Many DNA targeting drugs are currently in clinical use for treatment of different forms of cancer. 1,8Naphthalimide derivatives have emerged as important DNA intercalating class of compounds (Banerjee et al, 2013; Chen et al, 2018; Tomczyk and Walczak, 2018). The designed bis-naphthalimides exhibited enhanced DNA binding properties and are integral area of research in DNA intercalators (Banerjee et al, 2013; Tandon et al, 2017). One such compound is elinafide (LU79553) (3), which is a lead molecule in the bis-naphthalimide class of compounds.
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