Improved small-molecule macroarray platform for the rapid synthesis and discovery of antibacterial chalcones.

Bacterial resistance to current antibiotics is a major global health threat. Consequently, there is an urgent need for the identification of new antibacterial agents. We are applying the small-molecule macroarray platform to rapidly synthesize and screen compounds for activity against methicillin-resistant Staphylococcus aureus (MRSA).

Rapid identification of antibacterial agents effective against Staphylococcus aureus using small-molecule macroarrays.

There is an urgent, global need for the development of new antibacterial agents. We have applied the small-molecule macroarray approach to the synthesis and screening of antibacterial compounds active against the Gram-positive pathogen Staphylococcus aureus. Several macroarrays of 1,3-diphenyl-2-propen-1-ones (chalcones), cyanopyridines, and pyrimidines were synthesized on a planar cellulose support system on the order of days.

Discovery of fluorescent cyanopyridine and deazalumazine dyes using small molecule macroarrays.

[structure: see text] Small molecule macroarrays of cyanopyridines and deazalumazines were generated in high purities via spatially addressed synthesis on planar cellulose supports. Examination of the spectral properties of the heterocycles both on and off of the planar support revealed a set of promising new fluorescent dyes that exhibit high quantum yields, low pH dependence, and high sensitivity to solvent polarity.

Microwave-accelerated SPOT-synthesis on cellulose supports.

[reaction: see text] We demonstrate that microwave irradiation can dramatically accelerate reaction rates for spatially addressable library synthesis on planar membrane supports. The development of a robust support/linker system, microwave-assisted synthesis of small molecule test libraries, and methods for solid-phase scale-up on cellulose are described.