Fluorescent phosphoinositide 3-kinase inhibitors suitable for monitoring of intracellular distribution

The monitoring of the drug behavior and distribution in biological system can provide information whether drug reaches its desired target, and a biological rationale for the design of new therapeutics. We have developed a family of potent fluorescent PI3Kα inhibitors in which part of the fluorophore was engineered to be a pharmacophore capable of inhibiting PI3Kα. These xanthine derivatives are characterized by a donor–acceptor molecular structure, and changes in the electronic properties of the two variation points at R1 and R2 give rise to notable bathochromic shifts in the λem, abs and increase the value of ΦF. Further, we illustrated the use of E2 (PI3Kα/IC50 = 0.068 μM, T47D cell viability: IC50 = 0.9 μM) to block cancer cell proliferation and to monitor its subcellular localization by fluorescence microscopy.

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