## 1 Introduction  
In recent years, the process of discovering, designing, and optimizing drugs for more effective therapies has evolved rapidly. However, the costs associated with synthesizing and characterizing new compounds render drug development an expensive and labor-intensive endeavor, with many compounds failing to achieve commercial viability as drugs [1]. Consequently, a significant portion of the cost of developing new drugs is attributable to the synthesis and testing of substances that ultimately fail. Computer-aided methods such as quantitative structure-property relationship (QSPR) modeling, analysis, and molecular interaction investigations, including molecular docking, are increasingly being employed in the early stages of drug design, optimization, and synthesis to identify descriptors more closely associated with the target property. These innovative approaches to drug development rely heavily on the mathematical modeling of physicochemical features for chemical parameter prediction and computational structure analysis [2; 3]. In this sense, computational methods have proven to be powerful tools in the discovery of medicines and treatments, including those for cancer. Cancer is a chronic disease characterized by extensive phenotypic and genotypic diversity [4]. It is currently the second leading cause of death worldwide and is projected to surpass all other causes by 2060 [4; 5]. Natural products constitute a promising source for the development of antineoplastic drugs. A significant proportion of contemporary cancer therapies are derived from or inspired by the structure of natural products [6]. One such example is naphthoquinones, a class of naturally occurring compounds that exhibit structural diversity and significant potential for biological activity, including anticancer properties, as demonstrated by Nor-\(\beta\)-lapachone (NBL) [7; 8; 9]. The effectiveness of these compounds typically relies on their structural framework, particularly their redox systems, which include carbonyl groups that act as vital redox centers capable of generating reactive oxygen species (ROS). ROS production is intrinsically linked to the antitumor properties of quinone compounds. The reduction process that generates high levels of ROS can be biologically catalyzed by one- or two-electron reducing enzymes, such as NADPH-cytochrome P450 reductase and NAD(P)H quinone oxidoreductase 1 (NQO1), which function as redox agents [10]. ROS formation is associated with oxidative stress and alkylation, which involves the addition of alkyl groups to cellular nucleophilic molecules. These molecules include deoxyribonucleic acid (DNA), lipids, and proteins, among other biological macromolecules. Consequently, ROS leads to cytotoxicity and cell damage [11; 12]. Research has demonstrated that structural modifications of N\(\beta\)L, such as those in 2,2-dimethyl-3-((3-nitro-phenyl)amino)-2,3-dihydroonphtho[1,2-\(b\)]furan-4,5-dione (named here QPhNO\({}_{2}\)), shown in Figure 1, have displayed promising anticancer activity in in vitro models. QPhNO\({}_{2}\) can adopt different conformations, particularly due to the rotational freedom of the aromatic ring containing the nitro group in the -C-NH-C- linkage (see Figure S1 in Supporting Information), allowing for better adaptation to other molecules. However, its clinical application is limited due to its high lipid solubility, hydrophobicity, and non-specific dispersion, prompting researchers to explore alternative drug delivery methods [13]. Nanoencapsulation has been proposed as a promising strategy for administering anticancer drugs. The use of nanoparticles has been shown to enhance the therapeutic efficacy of anticancer drugs, facilitate controlled and sustained release, and reduce toxic side effects [13]. This system involves encapsulating specific components in suitable materials to protect them from adverse environmental factors.