Design and synthesis of substituted acridines as topoisomerase inhibitors

Abstract

Topoisomerase I is a key cellular enzyme that cuts DNA and makes it to wind and unwind, thereby plays an important role in transcription, replication and chromosome structure. To study the possible mechanism of cytotoxic potential exhibited by synthesized compounds 4b, 4d, 4e, 5b and 5g were subjected to DNA relaxation study.Based on the study, it is suggested that compounds 4b, 4d, 4e, 5b and 5g exhibit anticancer activity through Topoisomerase I inhibition.A total of 42 new substituted acridine derivatives bearing aryl ring through hydrazinyl linkage newlinehave been synthesized and evaluated for their antioxidant and anticancer activity against HeLa cancer cell line and HEK293 cell line by MTT assay. Cell migration assay was performed using 12 well culture plates. Cell cycle analysis was performed using FACS analysis against particular cell lines. Selective compounds were studied for their topoisomerase I inhibitory activity. In silico studies were also performed for understanding the binding and confirming the pharmacological observations.