Synthesis and Docking of Drug Delivery Anthraquinonylalkanamides

Overview

Anthraquinones are naturally occurring organic compounds with antibacterial, anticancer, and immunomodulatory properties, yet their current pharmaceutical use remains limited. This research study aims to design and synthesize integrated anthraquinone -based surfactants that act as both drug agents and delivery systems. In light of limitations with existing drug delivery systems (DDS), including poor absorptivity and distribution, and material instability, the creation of a biobased DDS would further the understanding and synthesis trends of drug delivery. Three surfactants, 1 -Anthraquinonyl dodecanamide (AQ12), tetradecanamide (AQ14), and hexadecanamide (AQ16), were synthesized by refluxing 1 -Aminoanthraquinone with acid chlorides, with purification via column chromatography. It was hypothesized that these surfactants would demonstrate improved druglikeness and transport properties compared to existing DNA - targeting drugs. Characterization was performed via IR spectroscopy, revealing successful synthesis. In silico study was conducted through DNA docking. AQ12 showed the highest binding affinity (S-score = -9.3050), attributed to hydrogen bonding and groove binding. AQ14 and AQ16 had weaker affinities due to steric hindrance from longer alkyl chains. All three surfactants showed statistically greater binding performance compared to ellipticine (p=1.51 × 10-7). Druglikeness and bioavailability were assessed using SwissADME, with AQ12 and AQ14 meeting Lipinski's Rule of Five, but AQ16 not due to excessive lipophilicity. AQ12 is the most promising candidate for future drug discovery and optimization. This study highlights the importance of balancing amphiphilicity in designing effective drug transport mechanisms. Future work will complete characterization, conduct in vitro testing, and with a focus on limiting steric hindrance in surfactants by tuning alkyl chain length.