In vitro antitumor evaluation of 4H-chromene-3-carbonitrile derivatives as a new series of apoptotic inducers

Abstract

Apoptosis is a naturally occurring process by which a cell is directed to programmed cell death. Chemotherapy drugs affect the cancer cells by the apoptotic induction. During the present study, a series of 4H-chromene-3-carbonitrile was synthesized by one-pot method as the inducers of apoptosis. Cytotoxic effects of six compounds of 4H-chromene-3-carbonitrile were evaluated against five tumor cell lines, with the help of colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Compound 4 showed significant cytotoxic activity and was selected for conjugation with the synthesized gold nanoparticles by aspartic acid. Also, we evaluated apoptosis induction capacity of the selected compound with the help of fluorescent dyes and DNA fragmentation. The result showed that the conjugated and non-conjugated forms of compound 4 were effective in inducing apoptosis and conjugated one had more efficiency and reduced the effective dose. Also, molecular modeling experiments involving compound 4 and colchicine binding site of tubulin dimer showed several strong hydrogen bonds and hydrophobic interactions to many important amino acid residues and GTP.

An Efficient, Green, Catalyst Free Synthesis and Crystallographic Study of Benzo-4h-Pyrans in Aqueous Medium

“…[20] Multi-component reactions (MCRs) have been successfully employed to generate highly diverse combinatorial libraries for high-throughput screening of biological and pharmacological activities. [21] A variety of natural and synthetic derivatives of chromene have important biological and pharmacological applications, such as antimicrobial, [22] anti-inflammatory, [23] antiproliferative, [24] antioxidant, [25] herbicidal, analgesic and anticonvulsant, [26] antitubercular, [27] anticoagulant, estrogenic antispasmolytic, estrogenic, [28][29][30][31][32][33][34][35][36][37] TNF-α inhibitor effects and activities, [38] as well as inhibitor of diabetes-induced vascular dysfunction. [39,40] Such diverse biological and pharmacological activities have made chromene derivatives important for further development in medicinal and organic synthesis studies.…”

One‐pot Synthesis of 2‐Amino‐4H‐chromenes Derivatives in Aqueous Solution of Choline Hydroxide

“…4H‐chromene skeleton is the key building block for many important natural heterocyclic products with wide pharmacological and biological activities [1–6] . Some of these natural compounds such as 2‐amino‐4H‐chromenes have showed antitumor, [7,8] antibacterial, [9–11] antiviral, [12] antioxidant, [13,14] anticoagulant [15,16] and antiallergenic activities [17] . In addition, they have also been utilized as laser dyes, [18] pigments, fluorescence markers [19] and cosmetics.…”

Microwave Accelerated Synthesis of 2‐Amino‐4H‐Chromenes Catalyzed by WELFSA: A Green Protocol

“…A wide range of chromene derivatives have been employed as a cosmetics, pigments, potential biodegradable agrochemicals, and for biological activities such as antioxidant, antiestrogen, anticonvulsant and neuroprotection . Some of the chromene derivatives also been proven to be an efficient DNA polymerase β‐inhibitors, apoptosis inducers, and anti‐trypanosomal agents . Due to this diverse area of application of chromenes, researchers are focusing on development of efficient and greener methodologies for the synthesis of chromene scaffolds .…”