Design, synthesis, and bioactivity of hydroxybenzoic acid derivatives and their polymer nanocomposites

Abstract

Cancer remains a global health challenge, necessitating a multifaceted approach integrating prevention, early detection, diagnosis, treatment, and ongoing research. Recent advancements in understanding the molecular intricacies of cancer have led to the development of targeted therapies and immunotherapy. However, the weakened immunity in cancer patients poses additional risks, with secondary opportunistic infections becoming a significant concern. Addressing this dual challenge requires innovative strategies, including in-silico methods to expedite drug discovery. In this study, novel compounds were designed and assessed for potential antimicrobial and anticancer properties through computational modeling. While in-silico predictions suggested promising candidates, experimental validation revealed discrepancies, emphasizing the complexity of predicting bioactivity solely through computational models. The computational method, however, showed that tri-substituted compounds are active and it was proven by experimental work. Compound C4 (benzene-1,3,5-triyl tris(3-hydroxybenzoate)) which is also a tri- substituted compound derived from 3-hydroxybenzoic acid showed great promise instead of the predicted compound C13 (benzene-1,3,5-triyl tris(3,4,5-trihydroxybenzoate)). Even though, compound C1 (3-acetylphenyl 3-hydroxybenzoate) was the leading candidate among other ester and amide compounds. Most of the compounds were non-toxic both in silico and in vitro corroborating the experimental and computational findings. Nonetheless, the synthesized compounds showed potential for further optimization as drug precursors. To enhance their activity and delivery, novel polymer nanoparticles were employed as carriers, resulting in improved efficacy in antimicrobial and anticancer assays. These findings underscore the importance of experimental validation and highlight the potential of nanomaterial-based drug delivery systems in addressing the dual challenge of cancer and microbial infections.