Design, synthesis and structure-activity relationship of novel semi-synthetic flavonoids as antiproliferative agents.

Various flavonoid scaffold based derivatives viz furochalcones (3a-e, 6a-d and 9a-d), furoflavones (10a-d, 11a-d, 12a-d, 18a&b), flavones (21a-d), furoaurones (13a,b, 14a-d and 15a-d) and 7-styrylfurochromones (22a-d and 25a-e) were designed and synthesized. The novel compounds were evaluated for their antiproliferative activity against a panel of 60 cancer cell lines comprising 9 types of tumors. Ten compounds belonging to the major subgroups of flavonoids viz furochalcones (3a, 3d, 6b, 9a and 9b), furoflavones (12a and 12c), furoaurones (15d), styrylfurochromones (25b and 25e) showed very promising activity. These active compounds were also evaluated in vitro as kinase inhibitors against CDK2/cyclin E1, CDK4/cyclin D1 and GSK-3ß and the best inhibition was displayed against GSK-3ß with the allylfurochalcone derivative 9b exhibiting 80% decrease in GSK-3ß catalytic activity. On the other hand, the styrylfurochromone 25e interestingly showed a 13% enhancement of GSK-3ß catalytic power and a 12% reduction in CDK4/cyclin D1 activity. Finally, the in vivo anti-tumor activity of 25e was evaluated against breast cancer induced in mice. The results showed a profound anti-tumor effect of 25e that accompanies a significant increase and decrease in the levels of GSK-3ß and cyclin D1, respectively.

Synthesis, in-vitro anticancer screening and radiosensitizing evaluation of some new N-(quinoxalin-2-yl)benzenesulfonamide derivatives.

The objective of this work is to synthesize and investigate the anticancer activity of a new series of sulfaquinoxaline derivatives by incorporating biologically active moieties (thiourethane, thiazole, imidazole, imidazopyrimidine, imidazopyrimido-pyrimidine, thienopyrimidine, benzopyrimidinone, benzothiazole, thiazole and pyridine moieties). All the newly synthesized compounds were evaluated for their in-vitro anticancer activity against human liver cell line (HEPG2). All the tested compounds showed comparable activity to that of the reference drug 5-fluorouracil (IC50=40 µM), and the most potent compounds were found to be compounds 4 and 17 (IC50=4.29 and 11.27 µM, respectively). On the other hand, the most potent compounds 4 and 17 were evaluated as radiosensitizing agents.

Synthesis and anticonvulsant activity of new thiazolidinone and thioxoimidazolidinone derivatives derived from furochromones.

Various new thiazolidinone and thioxoimidazolidinone derivatives were synthesized starting from 4,9-dimethoxy-5 H-furo[3,2-g][1]benzopyran-5-on-7-carboxaldehyde. The anticonvulsant activity of the synthesized compounds was evaluated. Most of the compounds showed anticonvulsant activity equal or superior to phenobarbital.

Synthesis of new 7-substituted 4-methylcoumarin derivatives of antimicrobial activity.

New cyclic derivatives derived from 4-methyl-7-coumarinyloxyacetic acid hydrazide have been synthesized. Some representative examples were screened for antimicrobial activity.

Synthesis, anticonvulsant and antimicrobial activities of certain new furochromones.

Some new substituted thiazolidinones, thioimidazolidinones and thiazolines have been synthesized from N1-substituted N2-(4-hydroxy-7-methyl-5H-furo[3,2-g] [1]benzopyran-5-on-9-yl)thioureas and monochloroacetic acid or alpha-halocarbonyl compounds. Some representative examples were tested for their anticonvulsant and antimicrobial activities.