Design, Synthesis and Biological Evaluation of Novel 5H-Chromenopyridines as Potential Anti-Cancer Agents

Abstract

A novel series of 5H-chromenopyridines was identified as anticancer agents in our continuing effort to discover and develop new small molecule anti-proliferative agents. Based on our initial lead SP-6-27 compound, we designed and synthesized novel tricyclic 5H-thiochromenopyridine and 5H-chromenopyridine analogs to evaluate the impact of an additional ring, as well as conformational flexibility on cytotoxic activity against human melanoma and glioma cell lines. All of the 5H-thiochromenopyridines have been achieved in good yields (89%-93%) using a single-step, three-component cyclization without the need for purification. The 5H-chromenopyridine analog of the potent 5H-thiochromenopyride was obtained in a good yield upon purification. All newly-prepared 5H-thiochromenopyridines showed good to moderate cytotoxicity against three melanoma and two glioma cell lines (3-15 μM). However, the 5H-chromenopyridine analogue that we prepared in our laboratory lost cytotoxic activity. The moderate cytotoxic activity of 5H-thiochromenopyridines shows the promise of developing chromenopyridines as potential anticancer agents.

A novel magnetic layered double hydroxide as potent mesoporous recyclable heterogeneous nanocatalyst for the synthesis of 1H‐chromeno[2,3‐b]pyridine‐3‐carbonitrile derivatives

“…[ 40 ] These compounds contain chromene scaffold in their framework that provides them with a variety of pharmacological activities as anticancer, anti‐HIV, diuretic, spasmolytic, antitumor, and antianaphylactic agents. [ 41,42 ] Furthermore, many of chromene derivatives are employed as valuable synthones in production of various industrial products such as cosmetics, pigments, [ 43,44 ] and biodegradable agrochemicals. [ 43 ] A wide variety of heterocyclic‐fused chromenes have been developed among which pyrano‐fused chromene derivatives have received enormous interest due to their wide range of biological activities including, antitumor, [ 45 ] anti‐HIV, [ 46 ] and antifungal activities.…”

“…[ 41,42 ] Furthermore, many of chromene derivatives are employed as valuable synthones in production of various industrial products such as cosmetics, pigments, [ 43,44 ] and biodegradable agrochemicals. [ 43 ] A wide variety of heterocyclic‐fused chromenes have been developed among which pyrano‐fused chromene derivatives have received enormous interest due to their wide range of biological activities including, antitumor, [ 45 ] anti‐HIV, [ 46 ] and antifungal activities. [ 47 ] Many of synthetic methods reported for the synthesis of various fused chromene derivatives including pyrano‐fused chromenes utilize one‐pot MCRs using different catalytic systems such as ionic liquids, [ 48 ] Mg/La mixed metal oxides, [ 49 ] H 6 P 2 W 18 O 62 .18H 2 O, [ 50 ] thiourea dioxide, [ 51 ] and silica‐grafted ionic liquid.…”

Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis

“…It is currently undergoing a phase-II clinical trial. Baed on this success, our group also recently reported a number of 4 H -chromene and chromenopyridine analogues with potential antiangiogenic or VDA activity [24,119,120].…”

Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening

“…Tetrahydro-4H-chromenes and dihydropyrano[c]-chromenes have diverse pharmacological potential as anti-allergenic, anti-proliferative, antibacterial, antiviral, antifungal, antioxidant, antitumor, and anticancer agents [6][7][8][9]. Examples include benzopyrans A and B, which possess anticancer activity [10], and compound C, which has antibacterial activity [11] (Figure 2). The discovery and clinical development of β-lactam antibiotics remains one of the major advances in modern medicine [12].…”