Chromenes: Potential New Chemotherapeutic Agents for Cancer

Abstract

Cancer is a major devastating disease, and is a leading cause of death worldwide. Despite the progress in cancer treatment, cancer mortality rate remains high. Therefore, the discovery and development of improved anticancer drugs to treat cancer are needed. 4H-chromenes have strong cytotoxicity against a panel of human cancer cell lines involving pathways that include microtubule depolarization and tumor vasculature disruption. A chromene analog, Crolibulin™ (EPC2407) is currently in Phase I/II clinical trials for the treatment of advanced solid tumors. This article reviews the general synthesis, biological activities and structure-activity relatinships of different classes of chromenes.

One-pot synthesis of tetrahydro-4H-chromenes by supramolecular catalysis in water

“…2-Amino-3-cyano -7,7-dimethyl-4-phenyl-5-oxo-4H-5,6,7,8-tetrahydrobenzopyran (a -3-cyano-7,7-dimethyl-4-(4-uorophenyl)-5-oxo-4H-5,6,7,8-tetrahydrobenzopyran (e -5,6,7,8-tetrahydrobenzopyran (h). White powder; yield: 94%; mp: 186 C; IR (KBr, n max , cm 6,7, 1,6,7, 1,6,7, 196.46, 171.57, 165.41, 159.88, 119.05, 110.25, 61.04, 51.71, 36.33, 36.15, 26.57, 20.25, 14.42 163.94,162.05,159.57,159.17,118.63,98.18,97.09,61.51,51.60,36.97,19.71,14.41;HRMS (ESI) …”

First intramolecular Diels–Alder reactions using chromone derivatives: synthesis of chromeno[3,4-b]xanthones and 2-(benzo[c]chromenyl)chromones

“…The effect of the addition of a series of Lewis acids was evaluated in solvent and solvent-free conditions, however, in all cases, the chromeno [3,4-b]xanthone 12a was only obtained in low yields (Table 1, entries [11][12][13][14][15][16]. Attempts to perform the reaction in solvent-free conditions were not advantageous affording compound 12a in only 29-37% yield (Table 1, entries 17 and 18).…”

“…Moreover, the prepared compounds can present enhanced biological properties since they combine the xanthone and chromene nucleus, and the benzochromene and chromone moieties in the same molecules (hybrid drug concept). [15][16][17][18] Results and discussion…”

“…Synthesis of (E)-2-(3-allyl-2-hydroxystyryl)-4H-chromen-4-one (16). The chromone derivative 15 (30 mg, 0.1 mmol) and 1,2,4-TCB (0.3 mL) were mixed in a closed glass vessel.…”

Enantioselective Organocatalyzed Synthesis of 2-Amino-3-cyano-4H-chromene Derivatives

“…Among these, anticancer activity [3] and their potential use as cognitive enhancers for the treatment of schizophrenia, myoclonus and different neurodegenerative diseases [4,5] are the most significant ones. Among the different types of chromenes, we want to focus on 2-amino-3-cyano-4H-chromene scaffolds.…”