Synthesis And Bioactive Evaluation Of Heterocompounds Possessing 1,3,4-Oxadiazole Moiety

The identification of new compounds for the treatment of cancer is an important undertaking in pharmaceutical research. As we know,1,3,4-oxadiazoles are an important class of heterocyclic compounds. The widespread use of them as a scaffold in medicinal chemistry establishes this moiety as a member of the privileged structures class. They possess a variety of biological activities. In particular, a few differently substituted 1,3,4-oxadiazoles have been found to exhibit anticancer activities. Further,1,3,4-oxadiazole heterocycles are very good bioisosteres of amides and esters, which can contribute substantially in increasing pharmacological activity by participating in hydrogen bonding interactions with the receptors.In view of above mentioned facts and an attempt to achieve new compounds with better anticancer activities, we synthesized one hundred and eleven heterocompounds possessing 1,3,4-oxadiazole moiety under the concept of structure-based drug design. The results were concluded as follows.Thirty-six 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 2-21 and 2-35 exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 2-21 exhibited significant telomerase inhibitory activity (IC50=2.3±0.07μM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 2-21 into the active site of telomerase (3DU6) to determine the probable binding model.Twenty-four new 2,5-disubstituted 1,3,4-oxadiazoles possessing quinoline and isoquinoline moieties were synthesized. The antiproliferative activities of these compounds were evaluated against gastric cancer cell SGC-7901 by applying the MTT method. Of all the studied compounds, three compounds (3-4a,3-6a and 3-8a) exhibited the best inhibitory activity against gastric cancer cell SGC-7901, which was more potent than 5-Fu. Structure-activity relationships were also discussed based on the experimental data obtained.Thirty-six new 1,3,4-oxadiazole thioether derivatives based on 1-(2-Hydroxyethyl)-2-methyl-5-nitroimidazole (metronidazole) scaffold have been synthesized and their in vitro anticancer activities against HepG2 (human hepatoma cells), SGC-7901 (human gastric cancer cells), and MCF-7 (human breast cancer cells) cell lines have been evaluated. Of all the studied compounds, the compound (4-13) having fluoro substituent at para position of the phenyl ring exhibited the most potent in vitro anticancer activities, are now undergoing further lead optimization in our laboratory for development as an anticancer agents.Fifteen Mannich bases of 5-(quinolin-2-yl)-1,3,4-oxadiazole-2(3H)-thione were designed, synthesized. The in vitro anticancer activities of these compounds were evaluated against HepG2, SGC-7901, and MCF-7 cell lines by MTT method. Of all the studied compounds, compounds having fluoro substituent at ortho position (5-4) and having chloro substituent at para position (5-9) of anilines displayed the most potent anticancer activities. These two compounds would be potential anticancer agents.