Synthesis and encapsulation of 1,3,5-triazine derivatives as anticancer agent

Abstract

The 1,3,5-triazine scaffold is known for its versatile biological activities especially as an anticancer agent, but a limitation of 1,3,5-triazine is the ability to reach cancer cells thus affecting its anticancer potency. In this work, the anticancer activity of twelve 1,3,5-triazine derivatives was evaluated against two colon cancer cell lines along with an investigation of a drug delivery system (DDS) using calcium citrate nanoparticles (CaCit NPs). Results from the biological evaluation showed that there was a variation in the anticancer activity of 1,3,5-triazine derivatives which some of them exhibited comparable activity to the reference drug cisplatin. Compound 2a and 3d were the two most cytotoxic derivatives and 2c and 3c, both bearing the o-hydroxyphenyl substituent, exhibited the lowest IC50 values around 20-27 µM. Moreover, the use of CaCit NPs as drug carrier for the selected 1,3,5-triazine derivative 2a was demonstrated. The preparation method of 1,3,5-triazine incorporated calcium citrate nanoparticles (CaCit-2a NPs) was optimised by selecting an appropriate solvent system, source of citrate ion, and synthesis time because these factors have effects on the morphology, size and %drug loading of nanoparticles. Upon using the optimised method, the obtained CaCit-2a NPs was monodispersed with particles size suitable to take advantage of the Enhanced Permeability and Retention (EPR) effect, possessed moderate %drug loading and showed controlled drug release behaviour under the acidic condition. The knowledge from this study could contribute to the future development of the 1,3,5-triazine-based anticancer drugs and provide calcium citrate nanoparticles as an emerging drug delivery platform to incorporate future drugs.