Benzimidazo[1,2-A]quinoxaline Based Library Synthesis and NCI60 Screening to Identify New Heterocyclic Scaffolds Having Anticancer Activity
Posted: 14 Feb 2020
Date Written: February 12, 2020
Cancer remains to be a leading cause of death worldwide resulting in continuous efforts to discover and develop highly efficacies cancer drugs. High Throughput Screening (HTS) of new heterocyclic compound libraries is one of the promising approaches which has provided several new lead molecules with novel mechanism of action. Based on the promising anticancer potential of imidazoquinoxaline as well as structurally similar imidazoquinoline derived structural scaffold, we prepared a set of benzimidazo[1,2-a]quinoxaline derivatives via two novel synthetic routes from commercially available starting materials in good to excellent yields, and evaluated their anti-cancer activity on NCI-60 cancer cell lines. The one dose (10 µM) anticancer screening of the synthesized compounds in NCI-60 cancer cell line panel revealed that the substituents have a significant role in the activity. In particular, the indole , imidazole as well as benzimidazole derivatives showed significant activity against at least one of the breast cancer cell lines, particularly on triple negative breast cancer (TNBC), MDA-MB-468 (inhibited 50% cell growth at 6.1, 2.7 and 3.3 µM, respectively). Currently, only a few treatment options are available for TNBC as it is more likely to recur than the other subtype of breast cancer. The lead compounds also exhibited excellent IC50 values against other breast cancer cell line, MCF-7. Furthermore, it was observed that these compounds were nontoxic to the normal cell lines (HEK293 cells). The IC50 values on healthy cells were at least 8-10 time more, offering new class of heterocycles which can be further developed as promising therapeutic for cancer treatment.
Keywords: Anticancer agents, Benzimdazo[1,2-a]quinoxaline, Heterocyles, NCI-60
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