Imidazoquinoxaline as a Privileged Fused Pharmacophore in Anticancer Drug Development: A Review of Synthetic Strategies and Medicinal Aspects

Abstract

Cancer, the uncontrolled growth of cells, is not a single but a multifaceted disorder with malignant behavior, metastasis, and invasion, medically known as malignant neoplasm. The number of cases and morbidity due to cancer is rising alarmingly worldwide, causing around 21 % annually. Imidazoquinoxaline is a privileged scaffold with a wide range of pharmacological activities that is well explored for its anticancer potential. As a synthon, imidazoquinoxaline presents a large number of possibilities for structural modifications, which have attained the attention of many researchers for the development of new anticancer molecules with diverse improved target specificity and efficiency. Development of imiquimod followed by EAPB203 and EAPB503 derivatives further enhanced the popularity of this structural pharmacophore. In this report, we have focused on the anticancer potential of newly reported imidazoquinoxaline derivatives, along with their SAR studies and therapeutic potential. We have also enlisted the synthetic schemes reported for the synthesis of imidazoquinoxaline derivatives. The lead structural features described in this review will assist the researchers in designing and developing the novel imidazoquinoxaline pharmacophore containing anticancer compounds possessing the potential to interfere with various factors or mediators which are responsible for the progression of cancer. This report will also help in identifying the potent compounds which can be further evaluated in clinical trials for the development of new anticancer drugs with minimal to no side effects.

Imidazo[1,2‐a]Quinoxaline‐2‐Carbonitrile Derivative (RA‐22) Inhibits Self‐Renewal and Growth of Cancer Stem and Cancer Cells via Downregulating AKT Pathway

“…Moreover, various imidazoquinoxalines also have some added commercial applications, such as chemiluminescent and dying agents. [5,6] Imidazo[1,2-a]quinoxalines are known to exhibit a diverse class of biological effects that include anticancer, [7] antifungal, [8] antiallergic, [9] rheumatoid arthritis, [10] antibacterial, [11] etc. One of the first known members of this class is Imiquimod (marketed as Aldara ® ), which got approval from the USFDA (1997) for the treatment of various types of cancers.…”

“…In comparison, other ring fusions like imidazo[4,5‐ b ]quinoxaline, imidazo[4,5‐ f ]quinoxaline, and imidazo[4,5‐ g ]quinoxaline are known to be found as mutagenic and carcinogenic agents in food products. Moreover, various imidazoquinoxalines also have some added commercial applications, such as chemiluminescent and dying agents [5,6] …”