Abstract
Twelve derivatives of biguanide-derived 1,3,5-triazines, a promising class of anticancer agent, were synthesised and evaluated for their anticancer activity against two colorectal cancer cell lines—HCT116 and SW620. 2c and 3c which are the derivatives containing o-hydroxyphenyl substituents exhibited the highest activity with IC50 against both cell lines in the range of 20–27 µM, which is comparable to the IC50 of cisplatin reference. Moreover, the potential use of the calcium citrate nanoparticles (CaCit NPs) as a platform for drug delivery system was studied on a selected 1,3,5-triazine derivative 2a. Condition optimisation revealed that the source of citrate ions and reaction time significantly influence the morphology, size and %drug loading of the particles. With the optimised conditions, “CaCit-2a NPs” were successfully synthesised with the size of 148 ± 23 nm and %drug loading of up to 16.3%. Furthermore, it was found that the release of 2a from the synthesised CaCit-2a NPs is pH-responsive, and 2a could be control released under the acidic cancer environment. The knowledge from this study is perceptive for further development of the 1,3,5-triazine-based anticancer drugs and provide the platform for the incorporation of other drugs in the CaCit NPs in the future.
Highlights
Cancer is a devastating disease with an increasing number of diagnosis and death every year
Six compounds with high %cytotoxicity were selected for further evaluation by varying the concentration between 0–100 μM to calculate the 50% cell-growth inhibition (IC50) values. The most potent anticancer agents were 2c and 3c, both having the o-hydroxyphenyl substituent with the IC50 of 25.25 ± 1.12 μM and 22.80 ± 1.06 μM for SW620 cell line, and at 26.29 ± 1.07 μM and 20.79 ± 1.07 μM for HCT116 cell line, respectively
Size and morphology of the synthesised products were recorded with JEOL JSM6480LV scanning electron microscope at 15kV; hydrodynamic size and zeta potential were measured with the Zetasizer Nano ZS, Malvern Instrument (IR of 1.660); functional groups were analysed by Thermo ScientificTM Nicolet 6700 FT-IR Spectrometer (Thermo Fisher Scientific, Waltham, MA, USA) with ATR mode; chemical changes or decomposition temperature by Perkin Elmer PyrisTM 1 TGA; elemental analysis by Thermo Flash 2000 CHNS/O analyser; and %cumulative drug release was measured with UV/Vis spectrometer (Hewlett Packard 8453, Agilent Technology, Santa Clara, CA, USA)
Summary
Cancer is a devastating disease with an increasing number of diagnosis and death every year. The 1,3,5-triazine scaffold has been reported to possess many biological activities especially anticancer activity [4]. A variety of synthetic routes exists for the 1,3,5-triazine derivatives, for example, three-component methods [5,6] or reactions between biguanides with alcohol [7,8], amide [9] or carboxylic acid derivatives [10,11]. Molecules 2021, 26, 1028 Molecules 2021, 26, 1028 reactions between biguanides with alcohol [7,8], amide [9] or carboxylic acid derivatives [10,11]. IOnfnleueinnfltiualeanstpiaelcatsopfetchteoEfPthReeEffPecRt iesffpecatrtiisclpeasrstiiczleeds s3i0z–e3d0030n–m30,0wnhmic,hwhhaicshbheeans breeepnorrteepdoartseda sausiatasbuleitarbalnegrea.nPgaer.tiPclaertsicizlee osiuztesioduetosifdtehiosfrtahnigseraanregepraorneeptroornaeptido cralepairdanccleeabryantchee bmyotnhoenmucolenaornpuhcalegaorcyptheasgyosctyemte [s1y7s,t1e8m]. The DDS based on the incorporation of a selected 1,3,5-triazine derivative into calcium citrate nanoparticles was investigated (Figure 1).
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