Synthesis and cytotoxic properties of novel (E)-3-benzylidene-7-methoxychroman-4-one derivatives

Abstract

Background and the purpose of the studyThere has been increscent interest in the field of cancer chemotherapy by discovery and development of novel agents with high efficacy, low toxicity, and minimum side effects. In order to find new anticancer agents, we replaced the pyrazolone part of well-known cytotoxic agent SJ-172550 with 7-methoxychroman-4-one. Thus, a novel series of 3-benzylidene-4-chromanones were synthesized and tested in vitro against human cancer cell lines.MethodsThe title compounds were prepared by condensation of 7-methoxychroman-4-one with suitable aldehydes in appropriate alcohol in the presence of gaseous HCl. The antiproliferative activity of target compounds were evaluated against MDA-MB-231 (breast cancer), KB (nasopharyngeal epidermoid carcinoma) and SK-N-MC (human neuroblastoma) cell lines using MTT assay.ResultsAlthough the direct analog of SJ-172550 (compound 5d) did not show any cytotoxic activity against tested cell lines, but 2-(2-chloro-6-methoxyphenoxy)acetic acid methyl ester analog 5c showed some activity against MDA-MB-231 and SK-N-MC cells. Further modification of compound 5c resulted in the 3-chloro-4,5-dimethoxybenzylidene derivative 5b which demonstrated better cytotoxic profile against all tested cell lines (IC50 values = 7.56–25.04 μg/ml).ConclusionThe results demonstrated that the cytotoxic activity of compound 5b against MDA-MB-231 and SK-N-MC cells is more than etoposide. Therefore, compound 5b prototype could be considered as novel cytotoxic agent for further developing new anticancer chemotherapeutics.

Synthesis and Biological Evaluation of 3-Benzylidene-4-chromanone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors

“…We synthesized a series of 3-benzylidene-4-chromanone derivatives (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) and evaluated their potential for DPPH free radical scavenging and α-glucosidase inhibitory activity. As a result, compounds 5, 13, 18, which possess a catechol moiety on the B-ring, were found to exhibit potent DPPH free radical scavenging and α-glucosidase inhibitory activities.…”

“…Compound 1a was commercially available and compounds 1b and c were synthesized from resorcinol according to the procedure of Foroumadi et al 21) With 1a-c in hand, each was condensed with benzaldehyde derivatives (2a-h) in the presence of piperidine to provide the 3-benzylidene-4-chromanone derivatives (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).…”

“…[10][11][12][13][14] Several natural and synthetic 3-benzylidene-4-chromanones are related structurally to flavonoids and were found to possess various biological properties such as antioxidant, antifungal, antiviral, anti-mutagenic, antiproliferative, anti-allergic, antihistaminic, anti-inflammatory, and monoamine oxidase inhibitory activity. [15][16][17][18][19][20][21][22][23][24] However, no systematically evaluated data are available on the inhibitory activity of α-glucosidase by 3-benzylidene-4-chromanone derivatives. 14) In order to further explore new biological activities of this family of compounds, we synthesized a series of 3-benzylidene-4-chromanone derivatives and investigated the structure-activity relationships (SAR) of these 3-benzylidene-4-chromanone derivatives to inhibit α-glucosidase and exhibit antioxidant activity.…”

Synthesis and Anti‐Cancer Activity Evaluation of New Dimethoxylated Chalcone and Flavanone Analogs

“…The chalcones 1a – f and flavanone derivatives 2a – e were synthesized starting from appropriate 2‐hydroxyacetophenone and dimethoxybenzaldehyde as outlined in Scheme . 3‐Chloro‐4,5‐dimethoxybenzaldehyde, 3‐bromo‐4,5‐dimethoxybenzaldehyde, and 1‐(2‐hydroxy‐4‐(2‐tetrahydro‐1 H ‐1‐pyrrolylethoxy)phenyl)‐1‐ethanone were prepared according to the literature methods .…”

Quantitative Structure-cytotoxicity Relationship of 3-Benzylidenechromanones

“…(3E)-2,3-Dihydro-3-(phenylmethylene)-4H-1-benzopyran-4-one [1], (3E)-2,3-dihydro-3-[(4-hydroxyphenyl) methylene]-4H-1-benzopyran-4-one [2], (3E)-2,3-dihydro-3-[(3,4-dihydroxyphenyl)methylene]-4H-1-benzopyran-4-one [3], (3E)-2,3-dihydro-3-[(4-methoxyphenyl)methylene]-4H-1-benzopyran-4-one [4], (3E)-2,3-dihydro-3-[(3,4-dimethoxyphenyl)methylene]-4H-1-benzopyran-4-one [5], (3E)-2,3-dihydro-3-[(4-dimethylaminophenyl)methylene]-4H-1-benzopyran-4-one [6], (3E)-2,3-dihydro-3-[(4-fluorophenyl)methylene]-4H-1-benzopyran-4-one [7], (3E)-3-[(4-chlorophenyl)methylene]-2,3-dihydro-4H-1-benzopyran-4-one [8], (3E)-2,3-dihydro-7-hydroxy-3-[(4-hydroxyphenyl)methylene]-4H-1-benzopyran-4-one [9], (3E)-2,3-dihydro-3-[(3,4-dihydroxyphenyl)methylene]-7-hydroxy-4H-1-benzopyran-4-one [10], (3E)-2,3-dihydro-7-hydroxy-3-[(4-methoxyphenyl)methylene]-4H-1-benzopyran-4-one [11], (3E)-2,3-dihydro-3-[(4-dimethylaminophenyl)methylene]-7-hydroxy-4H-1-benzopyran-4-one [12], (3E)-2,3-dihydro-7-methoxy-3-(phenylmethylene)-4H-1-benzopyran-4-one [13], (3E)-2,3-dihydro-3-[(4-hydroxyphenyl)methylene]-7-methoxy-4H-1-benzopyran-4-one [14], (3E)-2,3-dihydro-3-[(3,4-dihydroxyphenyl)methylene]-7-methoxy-4H-1-benzopyran-4-one [15], (3E)-2,3-dihydro-7-methoxy-3-[(4-methoxyphenyl)methylene]-4H-1-benzopyran-4-one [16] and (3E)-2,3-dihydro-3-[(4-dimethylaminophenyl)methylene]-7-methoxy-4H-1-benzopyran-4-one [17] (structures shown in Figure 1) were synthesized by base-catalyzed condensation of appropriate 4-chromanone with substituted benzaldehyde derivatives according to previous methods (19,20). All compounds were dissolved in DMSO at 40 mM and stored at -20˚C before use.…”