Synthesis of Novel Sesamol-Based Hybrids—In Silico Analysis and In Vitro Evaluation of Radical Scavenging Activity

New benzazole–sesamol derivatives 6a–8c were synthesized via an easily accessible reaction based on the coupling of Sesamol with in situ generated electrophilic N-alkoxycarbonylbenzazolium ions. This strategy successfully integrated benzothiazole, benzimidazole, and 5,6-dimethylbenzimidazole fragments with the biologically active natural lignan Sesamol. The structural integrity and the specific position of the newly formed C–C bond was confirmed by 1H-, 13C{1H}-, HSQC-NMR, FTIR, and HRMS analyses. The obtained compounds with yields in the range of 71–95% were evaluated for their in vitro radical scavenging activity and subjected to in silico predictions of mutagenicity and toxicity. Radical scavenging activity studies demonstrate that the introduction of a benzothiazoline ring (compounds 6a and 6b) enhances radical scavenging activity compared to Sesamol in the DPPH assay, outperforming the benzimidazole analogues. In silico analyses identified compounds 7b, 7c, 8a, 8b, and 8c as promising molecules due to the absence of mutagenic and irritant effects and their low toxicity profiles. In particular, compounds 7a, 7b, and 8a were found to be significantly safer than Sesamol. Compound 7a exhibited the highest safety profile, characterized by an LD50 value of 3046.92 mg/kg.