Design And Synthesis of New Potential Anticancer Agents

Abstract

newline Identification of a specific target is very important for safe and effective cancer chemotherapy. The tyrosine kinase (TK) family is considered as one of the important family members of the kinase family due to its important role in various cellular processes. Overexpression and dysfunction of tyrosine kinase receptors lead to the development of malignancy; thus, they are considered as one of the important targets for the development of anti-cancer molecules. Src is a prototypical member of the tyrosine kinase family who plays a critical role in the various cellular process like signal transduction, proliferation, survival, differentiation, etc. Mutation in Src leads to the development of different types of cancer. Three different series of benzothiazole-thiadiazol analogs (1a-7a, 1sa-7sa, and 1ib-4ib) were efficiently synthesized and evaluated for anti-cancer activity. The anti-cancer activities of all synthesized compounds were evaluated against two different cancer cell lines Caco-2 (colon) and MCF-7 (breast). Further validation of target was done by in-vitro enzyme inhibition study and insilico molecular docking studies. We found eight compounds namely 1a, 3a, 7a, 1sa, 3sa, 6sa, 1ib, and 3ib which were potent in anticancer evaluation, enzyme inhibition and also get high binding affinity in molecular docking studies. These results suggest that the potency of these compounds due to inhibition of the target Src-kinase. Finally, we want to conclude that these compounds should be further explored as Src inhibitors and they may have the potential to target Src mutated cancers. newline