Abstract 2721: Novel biisoquinoimidazolium-derivatives for breast cancer therapy

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Breast cancer is the most frequently diagnosed cancer in women. This cancer is classified according to its expression of hormone/growth factor receptors. It is divided into three groups: (i) Estrogen receptor (ER) and progesterone receptor (PR)-positive; (ii) Human epidermal growth factor receptor 2 (HER2)-positive; and (iii) ER, PR, and HER2-negative (triple-negative). Most chemotherapeutic anti-cancer drugs used in the clinical practice include an anti-estrogenic agent that interferes with ER and prevents tumor progression; however, it is still a big challenge to manage the triple-negative breast tumors. Mitosis and other distinct pathways of apoptosis are considered as a potential target for the development of novel anti-mitotic drugs. In the present investigation, we designed the biisoquinoimidazoliums class of drugs which is structurally similar to anti-mitotic drugs. We synthesized various derivatives of biisoquinoimidazoliums, tested their potency, and suitability as therapeutic agents in preclinical biological system using clonogenic assay. Results showed a strong growth inhibitory effect of these compounds on both triple-positive and triple-negative breast cancer cell lines in the following order: DHO2-93-1 ≥ DHO2-85-3 ≥ DHO2-75-3 ≥ DHO2-85-1. DH02-75-1 also showed some activity, while DHO2-75-2 and DHO2-107-1 did not show any growth inhibitory effect on these cells. From these results, we concluded that DHO2-93-1 may have therapeutic implication as a novel anti-tumor drug for the intervention of both triple-positive and triple-negative breast cancers. Citation Format: Satya Narayan, Aruna S. Jaiswal, Sukwon Hong. Novel biisoquinoimidazolium-derivatives for breast cancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2721. doi:10.1158/1538-7445.AM2014-2721