Assessment of metal-based dihydrofolate reductase inhibitors on a novel mesofluidic platform

Abstract

A new miniaturized micro sequential injection coupled with the lab-on-valve (µSIA–LOV) technique was full-blown to perform inhibitory studies on dihydrofolate reductase (DHFR). The system was used to evaluate the DHFR inhibition activity of metal-based anticancer compounds. The metal complexes exhibited IC50 values in the range 1.3 ± 0.3–108 ± 7 μM, with half of the complexes lying in the low μM range, i.e., 1.3 ± 0.3–4.4 ± 0.2 μM. For comparison, methotrexate (MTX), a known inhibitor of DHFR, has an IC50 value of 0.38 ± 0.06 μM. The µSIA–LOV is a versatile, robust, rapid, and easy to operate, allowing automated determination of DHFR inhibition. Moreover, the automated system requires very little sample (approximately 40 µL per analysis), uses minimal reagents (5 times less than the batch procedure used), and generates very little waste (around 1.2 mL per analysis) compared with batch methods, considerably reducing costs.