I-Li Chen

Synthesis and cytotoxic evaluation of some 4-anilinofuro[2,3-b]quinoline derivatives

Some 4-anilinofuro[2,3-b]quinoline derivatives were synthesized from dictamnine, a natural alkaloid, and evaluated for their cytotoxicity in the NCIs full panel of 60 human cancer cell lines derived from nine cancer cell types, including leukemia, non-small-cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer, and breast cancer. 1-[4-(Furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone (5) (mean GI50=0.025 μM), bearing an 4-acetylanilino substituent at C(4) of furo[2,3-b]quinoline, was more active than its 3-acetylanilino counterpart 7 (mean GI50=5.27 μM), and both clinically used anticancer drugs, N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide (m-AMSA; mean GI50=0.44 μM) and daunomycin (mean GI50=0.044 μM). Compound 5 was capable of inhibiting all types of cancer cells tested with a mean GI50 of less than 0.04 μM in each case except for the non-small-cell lung cancer (average GI50=1.75 μM). Although non-small-cell lung cancer is resistant to compound 5, the sensitivity within this type of cancer cells varies: HOP-62 (GI50<0.01 μM), NCI-H460 (GI50=0.01 μM), and NCI-H522 (GI50<0.01 μM) are very sensitive, while HOP-92 (GI50 = 12.4 μM) is resistant. Among these non-small-cell lung cancers, NCI-H522 was found to be very sensitive to 5, 8a, and 8b with a GI50 values of <0.01, 0.074, and <0.01 μM, respectively.

Synthesis and anti-inflammatory evaluation of 9-phenoxyacridine and 4-phenoxyfuro[2,3-b]quinoline derivatives. Part 2.

Mast cells, neutrophils and macrophages are important inflammatory cells that have been implicated in the pathogenesis of acute and chronic inflammatory diseases. To explore a novel anti-inflammatory agent, we have synthesized certain 9-phenoxyacridine and 4-phenoxyfuro[2,3-b]quinoline derivatives and evaluated their anti-inflammatory activities. The title compounds were synthesized by reaction of either 9-chloroacridine or 3,4-dichlorofuro[2,3-b]quinoline with appropriate Ar-OH and their anti-inflammatory activities were studied on inhibitory effects on the activation of mast cells, neutrophils and macrophages. Four 9-(4-formylphenoxy)acridine derivatives 2b-2e were proved to be more potent than the reference inhibitor, mepacrine for the inhibition of rat peritoneal mast cell degranulation with IC(50) values of 6.1, 5.9, 13.5, and 4.7 microM, respectively. Compounds 2c, 3b, 3c, and 5a also showed potent inhibitory activity (IC(50)=4.3-18.3 microM) for the secretion of lysosomal enzyme and beta-glucuronidase from neutrophils. In addition, 2d, 3a, and 4 inhibited TNF-alpha formation from the N9 cells (the brain resident macrophages) with IC(50) vales less then 10 microM. These results indicated that acridine derivatives exhibited more potent anti-inflammatory activities than their respective furo[2,3-b]quinoline counterparts (4 vs 9; 5a vs 10a; 5b vs 10b).