Synthesis and cytotoxicity of 2-phenylquinazolin-4(3H)-one derivatives.

Thirty 2-phenylquinazolin-4(3H)-one derivatives were prepared and their cytotoxic activities were tested in five human tumor cell lines. Some compounds (5e, 5k, 5t, 6c and 6f) showed relatively high cytotoxic activity. Especially, compound 6c showed the most cytotoxicity against all cell lines tested among the synthesized derivatives, and the inhibitory activity of 6c against HeLa cell was higher than that of adriamycin.

Antitumor effects of a novel benzonaphthofurandione derivative (8e) on the human colon cancer cells in vitro and in vivo through cell cycle arrest accompanied with the modulation of EGFR and mTOR signaling.

Benzonaphthofurandione has been considered as an important class of naturally occurring and synthetic compounds having a variety of biological functions. In this study, we evaluated the antitumor effects of 3-[2-(dimethylamino)isopropoxy]-1-hydroxybenzo[b]naphtho[2,3-d]furan-6,11-dione (8e), a novel benzonaphthofurandione derivative, on the growth of colorectal cancer HCT 116 cells both in vitro culture and an in vivo animal model. Compound 8e exhibited the potential growth inhibition of the colon cancer cells in a concentration-dependent manner.

Synthesis and evaluation of benzoxazole derivatives as 5-lipoxygenase inhibitors.

5-Lipoxygenase (5-LOX) is important enzyme in the biosynthesis of leukotrienes, and is a potential target in the treatment of asthma and allergy. We designed and synthesized a series of benzoxazoles and benzothiazoles as 5-LOX inhibitors. Fourteen compounds prepared showed the inhibition of LTC4 formation with IC(50) value of 0.

Synthesis and T-type calcium channel blocking activity of novel diphenylpiperazine compounds, and evaluation of in vivo analgesic activity.

Novel diphenylpiperazine derivatives were synthesized and evaluated for their inhibitory activity against T-type calcium channel by whole-cell patch clamp recordings on HEK293 cells. Among the test compounds, 2 and 3d were effective in decreasing the response to formalin in both the first and second phases and demonstrated antiallodynic effects in a rat model of neuropathic pain.

Synthesis and bradykinin inhibitory activity of novel non-peptide compounds, and evaluation of in vivo analgesic activity.

A series of novel non-peptide diamide compounds was synthesized and evaluated as antibradykinin agents by utilizing guinea-pig ileum smooth muscle. Among the final compounds, (Z)-4-(4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)-4-oxo-N-(4-phenylbutan-2-yl)but-2-enamide showed most favorable bradykinin inhibitory activity and demonstrated analgesic efficacies in the rat models of inflammatory and neuropathic pain.

Synthesis of isoquinolinone-based tetracycles as poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors.

The isoquinolinone-based tetracyclic compounds were designed and synthesized and their PARP-1 inhibitory activity was evaluated. Most of synthesized compounds showed fairly good activity. Also the most active compound 6 showed its activity on potentiation of anticancer agents, temozolamide and etoposide, by 1.

Synthesis of 1-/2-substituted-[1,2,3]triazolo[4,5-g]phthalazine-4,9-diones and evaluation of their cytotoxicity and topoisomerase II inhibition.

Studies on antitumor heterocyclic quinones containing nitrogens revealed that the number and position of nitrogens on the heterocyclic ring have significance on cytotoxicity of quinones. In our continuous effort to find more cytotoxic quinone compounds, we designed triazolophthalazine analogues in order to introduce more nitrogens on the heterocyclic quinones. 1-/2-Substituted-[1,2,3]triazolo[4,5-g]phthalazine-4,9-diones were synthesized by 1,3-dipolar addition of phthalazine-5,8-dione and 4-methoxybenzyl azide by modification of previously reported method.

Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones.

Benzofuroquinolinediones (7c and 7d) were synthesized by base-catalyzed condensation of dichloroquinolinediones with phenolic derivatives. Their dialkylaminoalkoxy derivatives (8i-8p) were prepared by reaction with various dialkylaminoalkyl chlorides. The cytotoxicity of the synthesized compounds was evaluated against eight types of human cancer cell lines, and their topoisomerase II inhibition was assessed.

Synthesis and cytotoxicity evaluation of substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzofluorene-5,6-diones.

The substituted pyridazino[4,5-b]phenazine-5,12-diones and tri/tetra-azabenzo[a]fluorene-5,6-diones were synthesized from 6,7-dichlorophthalazine-5,8-dione and 6,7-dichloroquinoline-5,8-dione, respectively. The cytotoxic activities of the prepared compounds were evaluated by an SRB (Sulforhodamine B) assay against the following human cancer cell lines: A549 (lung), SK-OV-3 (ovarian), SK-MEL-2 (melanoma), XF 498 (CNS), and HCT 15 (colon). Almost all synthesized pyridazino[4,5-b]phenazine-5,12-diones (7a-j) presented higher cytotoxicity than that of doxorubicin (IC(50)=0.

Synthesis of 6-chloroisoquinoline-5,8-diones and pyrido[3,4-b]phenazine-5,12-diones and evaluation of their cytotoxicity and DNA topoisomerase II inhibitory activity.

The substituted chloroisoquinolinediones and pyrido[3,4-b]phenazinediones were synthesized, and the cytotoxic activity and topoisomerase II inhibitory activity of the prepared compounds were evaluated. Chloroisoquinolinediones have been prepared by the reported method employing 6,7-dichloroisoquinoline-5,8-dione. The cyclization to pyrido[3,4-b]phenazinediones was achieved by adding the aqueous sodium azide solution to the dimethylformamide solution of corresponding chloroisoquinoline-5,8-dione.