New imidazo[1,2-a]quinoxaline derivatives: Synthesis and in vitro activity against human melanoma

Abstract

New imidazo[1,2-a]quinoxaline analogues have been synthesized in good yields via a bimolecular condensation of 2-imidazole carboxylic acid, followed by a coupling with ortho-fluoroaniline and subsequent substitution on the imidazole ring by Suzuki Cross-coupling reaction using microwave assistance. Antitumor activities of these derivatives were evaluated by growth inhibition of A375 cells in vitro. All compounds exhibited high activities compared to imiquimod and fotemustine used as references.

Imidazoquinoxaline derivative EAPB0503: A promising drug targeting mutant nucleophosmin 1 in acute myeloid leukemia

“…In this report, we examine the effects of EAPB0503 and EAPB0203, 2 imidazoquinoxaline agents, on AML cell lines. Imidazoquinoxalines have arisen as promising anticancer drugs on the basis of their in vitro activity in T‐cell leukemia and chronic myeloid leukemia and their in vivo activity in melanoma . We show that EAPB0503 has a specific growth‐inhibition effect on NPM1c OCI‐AML3 and IMS‐M2 cells in a dose‐ and time‐dependent manner.…”

“…20 Imiquimod analogues, called imidazoquinoxalines, have been synthesized 21 ; among them, 1-(2-phenylethyl)-N-methylimidazo[1,2-a]quinoxalin-4-amine (EAPB0203) and 1-(3-methoxyphenyl)-N-methylimidazo[1,2-a]quinoxalin-4-amine (EAPB0503) have been reported with promising antitumor activity. 22,23 Indeed, EAPB0203 displayed pronouncedly higher in vitro potency against melanoma and adult T-cell leukemia cells in comparison with imiquimod. 23,24 Later, EAPB0503 showed 10-fold higher cytotoxicity than EAPB0203 against melanoma cells.…”

“…Imiquimod is a toll‐like receptor 7 immunomodulator used to treat certain skin cancers and genital warts . Imiquimod analogues, called imidazoquinoxalines, have been synthesized; among them, 1‐(2‐phenylethyl)‐ N ‐methylimidazo[1,2‐ a ]quinoxalin‐4‐amine (EAPB0203) and 1‐(3‐methoxyphenyl)‐ N ‐methylimidazo[1,2‐ a ]quinoxalin‐4‐amine (EAPB0503) have been reported with promising antitumor activity . Indeed, EAPB0203 displayed pronouncedly higher in vitro potency against melanoma and adult T‐cell leukemia cells in comparison with imiquimod .…”

EAPB0503, a novel imidazoquinoxaline derivative, inhibits growth and induces apoptosis in chronic myeloid leukemia cells

“…quinoxalin-4-amine) and EAPB0503 (1-(3-methoxyphenyl)-N-methylimidazo[1,2-a]quinoxalin-4-amine) were synthesized as described by Deleuze-Masquefa et al [8,14]. The synthesis of EAPB0503 was subsequently optimized by microwave-assisted chemistry (Fig.…”

“…Imiquimod is a tolllike receptor 7 (TLR-7) modulator [9] and an immunomodulatory agent [10] used topically to treat certain types of skin cancers [11] and genital warts [12], acting through the cytokine-dependent activation of helper T cells [13]. A series of in-vitro experiments have reported promising antitumoral activities of two novel imidazoquinoxaline compounds, EAPB0203 and EAPB0503, on different cancer cell lines [14][15][16]. EAPB0203 showed a high in-vitro potency against the A375 human melanoma cell line and was found to be 45-fold more effective than imiquimod [15].…”