Synthesis and biological evaluation of novel hydroquinone dimethyl ethers as potential anticancer and antimicrobial agents

The synthesis of two novel series of quinol dimethyl ethers linked to either various functionalities or to some biologically active nitrogenous heterocycles is described. Nine of the newly synthesized quinol dimethyl ethers 5a, b, 9b, 10a, d, 12a, b, and 13a, b were selected by the NCI and were tested initially at a single high dose (10 mu M) in the full NCI 60 cell panel. Four of the screened quinol dimethyl ethers bearing unsubstituted phenylhydrazone 5a, 4-chlorophenylhydrazone 5b, 4-chlorophenyl-3-sulfanyl-1,2,4-triazole 9b, as well as 4-chloroanilino-1,3,4-oxadiazole 12b moieties satisfied the threshold antitumor screen. 4-Chlorophenylhydrazone 5b showed very promising results and accordingly was chosen for in vivo antitumor screening. Thus, compound 5b of the series could be considered as the potential lead for development of novel anticancer agents. In addition, compounds 5a-c, 6a-c, 9a-c, 10a, b, d, e, g, h, 11a-c, 12a-c, and 13a-c were screened for their in vitro antimicrobial activity. Some of the tested compounds exhibited special high activity comparable to the reference ampicillin against Pseudomonas aeruginosa and Escherichia coli.