Byung-Ho Chung

Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents

To investigate the structure-activity relationship of 7,8-dimethoxy-2- methyl-3-(4,5-methylenedioxy-2-vinylphenyl)isoquinolin-1(2H) -one 2, diverse substituted 3-arylisoquinolines were synthesized and tested in vitro antitumor activity against five human tumor cell lines. The results showed a broad antitumor spectrum for a series of 3-arylisoquinolines.

Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives

In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.721) was obtained through CoMFA.

Synthesis and antitumor activity of 3-arylisoquinoline derivatives

In order to study the structure-activity relationship of 7,8-dimethoxy-2-methyl-3-(4,5-methylen-edioxy-2-vinylphenyl)isoquinoline-1 (2H)-one (2), which has exhibited significant antitumor activity, chemical modifications of2 were performed to yield the corresponding products (3–7). Further systematic uses of an efficient procedure for the synthesis of 3-arylisoquinoline derivatives produced the substituted compounds (9a−9g), which were tested forin vitro antitumor activity against five different human cancer cell lines.

Synthesis of benzo[c]phenanthridine derivatives and theirin vitro antitumor activities

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screenedin vitro antitumor activities against five different cell lines as well as12. Among them the representative cytotoxic results are shown as follows;p-quinone (11) [ED50 (A549=0.22 μg/ml), (HCT15=0.21 μg/ml), fagaridine (1) (HCT 15=0.41 μg/ml), olefin (6) (HCT 15=0.06 μg/ml), acetal (7) (SKMEL-2=0.07 μg/ml), dihydrofagaridne (10) (A549=0. 38 μg/ml), 10-hydroxyfagaridine (12) (A 549=0.45 μg/ml). From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significantin vitro antitumor activity.

Structure-activity relationship studies of isoquinolinone type anticancer agent

Substituted isoquinolin-1-ones (1) were synthesized to test theirin vitro anticancer activity. 3-Biphenyl-N-methylisoquinolin-1-one (7) showed the most potent anticancer activity against five different human cancer cell lines.

Design and Synthesis of Novel Antidiabetic Agents

The synthesis and structure-activity relationships of a novel series of substituted quercetins that activates peroxisome proliferator-activated receptor gamma (PPARγ) are reported. The PPARγ agonistic activity of the most potent compound in this series is comparable to that of the thiazolidinedione-based antidiabetic drugs currently in clinical use.

Synthesis and structure-activity relationship studies of 2,3-dihydroimidazo[2,1-a]isoquinoline analogs as antitumor agents

Abstract5-Aryl-2,3-dihydroimidazo[2,1-a]isoquinolines were reported to have strong antitumor activity and one of the derivatives such as 5-[4′-(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-a] isoquinoline (1, SDZ 62–434) was found to be more effective than the clinical cytostatic agent edelfosine (2) inin vitro andin vivo assays. Currently SDZ 62–434 is in clinical trials in Europe. The structure-activity relationship studies of SDZ 62–434 showed that compounds with substitution on ring A were less active than the lead compound. Ring B in SDZ 62–434 was essential for the activity because compounds without B ring had no antitumor activity. Among the 3-arylisoquinolin-1-one derivatives, 3-[4′-(piperidonomethyl)phenyl] substituted analog had no antitumor activity but simple phenyl substituted compound, such as4, showed the most potent antitumor activity in various human tumor cell lines.

Synthesis and structure-activity relationship studies of substituted isoquinoline analogs as antitumor agent

A number of substituted isoquinolin-1-ones, possible bioisosteres of the 5-aryl substituted 2,3-dihydroimidaz[2,1-a]isoquinolines, were synthesized and tested for their antitumor activity against five different human tumor cell lines.O-(3-hydroxypropyl) substituted compound (15) exhibited the best antitumor activity which is 3–5 times better than 5-[4′-(piperidinomethyl) phenyl]-2,3-dihydroimidazo[2,1-a]isoquinoline (1).

Synthesis of Mannich bases of antineoplaston A10 and their antitumor activity.

Some Mannich bases of Antineoplaston A10 which is antitumor agent under clinical investigation were synthesized and tested for cytotoxicity. The tested compounds (2a, 2b, 2d) showed good activity comparable to that of carboplatin.

Synthesis of antineoplaston A10 analogs as potential antitumor agents.

Several aniline mustard analogues were obtained by introducingN,N-bis(2-chloroethyl)amino moiety to phenyl ring of A10 analogues in order to increase reactivity of A10 analogs and selectivity into DNA. Thein vitro antitumor activity of synthesized compounds was evaluated using five different solid tumor cell lines by SRB method. Aniline mustard analogues exhibited more potent antitumor activity than A10 analogs. Especially,m-aniline mustard of benzoyl analogue displayed remarkable antitumor activity.