High-throughput screening of telomerase inhibitors in actinomycetes fermentation broth / 中国药理学通报

Aim To discover specific telomerase inhibitors by high-throughput screening in the more than 2 000 strains of actinomycetes fermentation broth.Methods After verifying the three kinds of screening models for telomerase inhibitor by yeast PCR,the three yeast strains were inoculated overnight into yeast liquid culture which was lacking in histidine and contained 3-AT.Then concentration of yeast strains in culture liquid and dosage of screening sample were regulated for better adjustment to the high-throughput screening.At last the adjusted liquid culture containing yeast strain piped to 96-well plates,drug samples and control article were also added,then the yeast was incubated in the thermostat oscillator.At the same time OD_(595nm) of the yeast liquid was measured every 12 h by using Multifunctional Microplate Analyzer,and the samples whose inhibitory efficiency was over 0.45 were selected for secondary screening.Results The high-throughput screening method related to yeast three-hybrid system was effective in screening samples that had potential telomerase inhibitory ability.The initial concentration of yeast liquid OD_(595nm) was 0.04 and the best dosage of samples was 5 ml.14 active samples,whose inhibitory efficiency was over 0.45,were founded after primary and secondary screening.Conclusions High-throughput screening method related to yeast three-hybrid system is simple and stable in discovering telomerase inhibitors,and 14 new antitumor compounds are identified,which lays the foundation in the development of new anti-tumor agents.

Design,Synthesis and Biological Activity of Cationic Porphyrins Bearing Mixed 3-Quinolyl and 4-Pyridyl Meso Groups / 中国药科大学学报

AIM:To search for the potent telomerase inhibitors with structures of cationic porphyrins to improve the interactions between G-quadruplex and porphyrins by systematically varying the meso substituents.METHODS:Porphyrins bearing mixed 3-quinolyl/4-pyridyl meso groups were synthesized using the Adler-Longo method by condensation of aldehydes with pyrrole,and then followed by methylation and ion exchange.The compounds were tested for the telomerase inhibitory activity and c-Myc inhibitory activity.RESULTS:All compounds were found to be potent and approximately equivalent in terms of their ability to inhibit the action of telomerase in a cell-free assay.Compound 4 had the best inhibitory activity on c-Myc.CONCLUSION:Cationic porphyrins would be the potential anticancer candidates.

Preparation and Bioactivity of Cationic Porphyrins Bearing Mixed 3-quinolyl and 3-pyridyl Meso Groups / 中国药科大学学报

AIM: To search for the potent telomerase inhibitors with structures of cationic porphyrins to improve the interactions between G-quadruplex and porphyrins by systematically varying the meso substituents. METHOD: Porphyrins bearing mixed 3-quinolyl/3-pyridyl meso groups were synthesized using the Adler-Longo method by condensation of aldehydes with pyrrole, followed by methylation and ion-exchange. The compounds were tested for the telomerase inhibitory activity and c-Myc inhibitory activity. RESULT: All compounds were found to be potent and approximately equivalent in terms of their ability to inhibit the action of telomerase in a cell-free assay. Compound 4 had the best inhibitory activity on c-Myc.