Structure-Based Design and Molecular Docking Study of Oxazole<span lang="DE">–Coumarin Hybrid Compounds as Tubulin Inhibitors

The successful design of targeted drug delivery systems hinges critically on the selection of an appropriate nanocarrier to enhance both therapeutic efficiency and specificity. A thorough understanding of the geometric and electronic structures, as well as the chemical reactivity profiles of both drug candidates and their potential carriers in physiological environments, is essential for predicting their behavior and interactions. In this study, we propose Single-Walled Carbon NanoTubes (SWCNTs) as highly suitable carriers for a series of coumarin derivatives (X-۳-((۲-(benzo[d]oxazole-۲-yl)phenoxy)methyl)-۲H-chromen-۲-one) (BOPMC), where X denotes the substitution groups) substituted with chlorine (–Cl), methyl (–CH₃), methoxy (–OCH₃), and hydroxyl (–OH) groups—all of which exhibit promising anticancer properties. Using Density Functional Theory (DFT) calculations, we demonstrate that these substituents induce distinct variations in the derivatives’ electronic structures, chemical reactivity descriptors, and the nature and strength of noncovalent interactions with the SWCNT surface. Among the investigated compounds, the chloro-substituted coumarin derivative emerges as the most reactive, characterized by a more negative chemical potential (μ = –۳.۷۸۱ eV), lower chemical hardness (η = ۳.۰۰۷ eV), and elevated electrophilicity index (ω = ۲.۳۷۷ eV), indicating a strong tendency for adsorption onto the SWCNT surface upon encapsulation and tubulin after its release to this protein. The formation of a stable noncovalent assembly in the internal configuration of the SWCNT is confirmed by a highly negative adsorption energy (Eads + bsse = – ۲۳.۲۹۱ kJ/mol). Furthermore, molecular docking analysis reveals that the interaction energy of the oxazole–coumarin derivative with tubulin (–۳۳.۴۴ kJ/mol) arises primarily from steric contacts, hydrogen bond donor/acceptor interactions, and electrostatic potentials. Collectively, our findings establish SWCNTs as effective nanocarriers for oxazole–coumarin derivatives, with the chloro-substituted compound standing out as a promising prodrug candidate for the development of tubulin-targeted anticancer therapies.

کلیدواژه ها:

Single-Walled Carbon NanoTube (SWCNT) ، Density Functional Theory (DFT) ، Chemical reactivity descriptors ، Tubulin-targeted therapy ، Oxazole-Coumarin derivatives