NEW ANTIFOLATE 4,4'-DIAMINODIPHENYL SULFONE SUBSTITUTED 2,4-DIAMINO-5-BENZYLPYRIMIDINES - PROOF OF THEIR DUAL-MODE OF ACTION AND AUTOSYNERGISM

New 4,4'-diaminodiphenylsulfone substituted 2,4-diamino-5-benzylpyrimi dines were synthesized. These compounds are highly active inhibitors O f both bacterial dihydrofolate reductase (DHFR) and dihydropteroic aci d synthase (SYN). The simultaneous inhibition of both enzymes leads to autosynergism in whole cells in the same way as known for combination s of sulfonamides with trimethoprim. The inhibitory activity is demons trated in cell-free systems of DHFR and SYN derived from various speci es (M. lufu, E. coli, C. albicans) and in whole cell systems of the my cobacterial strain M. lufu. The compounds are rare examples for the co mbination of two mechanisms of action in one molecule.