Benzopyran Derivatives Research Articles

2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis in human endometrial cancer cells

Objectives The present study was undertaken to explore the mechanism of anti-proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3-phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in Ishikawa and human primary endometrial adenocarcinoma cells. Methods Transcriptional activation assays were performed using luciferase reporter system and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The stage of cell cycle was determined by flow-cytometry and real time analysis of cyclinE1 and cdc2 genes. The apoptotic effects were measured by AnnexinV/PI staining and TUNEL. The expression of PCNA, cyclinD1, pAkt, XIAP, cleaved caspase-9, -3, PARP, Bax and Bcl2 were determined by immunoblotting. The caspase-3 activity and mitochondrial membrane potential were measured by colorimetric assay. Results All three compounds inhibited E 2-induced ERE- and AP-1-mediated transactivation and proliferation in endometrial adenocarcinoma cells dose-dependently. Compound D1 caused the arrest of cells in the G 2 phase while D2 and D3 caused arrest in G 1 phase of the cell cycle. All compounds interfered with Akt activation, decreased XIAP expression leading to an increased cleavage of caspase-9, -3, PARP, increased Bax/Bcl2 ratio and caspase-3 activity. Conclusion Findings suggest that benzopyran derivatives inhibit cellular proliferation via modulating ER-dependent classical and non-classical signaling mechanisms, interfere with Akt activation and induce apoptosis via intrinsic pathway in endometrial adenocarcinoma cells.

Synthesis and antimalarial evaluation of novel benzopyrano[4,3-b]benzopyran derivatives

7-Methoxyflavenes and 5,7,8-trimethoxyflavenes were found to undergo stereoselective acid-catalyzed rearrangement to generate the benzopyrano[4,3-b]benzopyran ring system present in the natural product, dependensin. Dependensin and its analogs were subjected to antimalarial growth inhibition assays against Plasmodium falciparum and found to have IC50 values ranging between 1.9 and 3.9μM.

ChemInform Abstract: Asymmetric Inverse‐Electron‐Demand Hetero‐Diels—Alder Reaction of Six‐Membered Cyclic Ketones: An Enamine/Metal Lewis Acid Bifunctional Approach.

AbstractThe reaction of cyclic ketones with β,γ‐unsaturated α‐ketoesters under catalysis of yttrium triflate and optically active primary amine PYR affords benzopyran, pyranopyran, and pyranothiopyran derivatives in a highly stereo‐ and chemoselective manner.

ChemInform Abstract: Chiral Organic Contact Ion Pairs in Metal‐Free Catalytic Asymmetric Allylic Substitutions.

AbstractAn unprecedented asymmetric Broensted acid‐catalyzed intramolecular alkylation leading to benzopyran derivatives is developed.

English

Citrus fruits have long been recognized as containing valuable sources of important nutrients which are biologically active in humans. Citrus fruits, such as oranges, contain compounds called phytochemicals that can be included into three major groups: the flavonoids, limonoids and carotenoids. The flavonoids are a group of benzopyran derivatives which occur widely in plants. The flavonoids typically consist of a benzene ring fused with the heterocyclic six-membered ring containing an oxygen atom. As citrus has an antioxidant’s potential, we want to evaluating its useful effect on spermatogenesis and sperm parameters. Wistar male rat (n=30) were allocated into three groups, control (n=10) and test groups (n=20), that subdivided into groups of 2 that received citrus extract powder (400 and 600 mg/rat) for 30 consequence day. Animals were kept in standard conditions. In twentieth day the testes tissue of rats in whole groups were removed and sperm was collected from epididymis and prepared for analysis. TAC, SOD levels and percentage of sperm viability and motility in both test groups significantly increased (p<0.05) in comparison to control group, whereas, sperm concentration, morphology and testes weights in both experimental and control group were similar. The level of MDA in both extract groups were significantly decreased (p<0.05). Results revealed that administration of 600 mg/kg/day citrus extract significantly increased the TAC, SOD levels and sperm percentage, viability, motility and decreased MDA levels. This suggested that citrus may be promising in enhancing sperm healthy parameters.     Key words: Anti-oxidative, citrus, spermatogenesis, super oxide dismutase, testis.

ChemInform Abstract: Synthesis of Tetrahydrobenzo[b]pyran Derivatives Catalyzed by Aliquat®336 in Water under Microwave Irradiation.

AbstractA simple synthesis of a series of benzopyran derivatives (35 examples) via a microwave‐acellerated multicomponent reaction is given.

Modulation of the 6-position of benzopyran derivatives and inhibitory effects on the insulin releasing process

The synthesis of different series of 4- and 6-substituted R/ S-3,4-dihydro-2,2-dimethyl-2 H-1-benzopyrans is described. All of these new benzopyran derivatives were bearing, at the 4-position, a phenylthiourea moiety substituted on the phenyl ring by a meta or a para-electron-withdrawing group such as Cl or CN. The study aimed at exploring the influence of the nature of the substituent at the 6-position in order to develop new benzopyran-type K ATP channel activators exhibiting an improved selectivity towards the insulin secreting cells. The original compounds were examined in vitro on rat pancreatic islets (inhibition of insulin release) as well as on rat aorta rings (vasorelaxant effect) and their activity was compared to that of the reference K ATP channel activators (±)-cromakalim, (±)-pinacidil, diazoxide and to previously synthesized cromakalim analogues. Structure–activity relationships indicated that the inhibitory effect on the insulin secreting cells was related to the lipophilicity of the molecules and to the size of the substituent located at the 6-position. A marked inhibitory activity on the insulin secretory process was obtained with molecules bearing a bulky tert-butyloxycarbonylamino group at the 6-position ( 20– 23). The latter compounds were found to have the same efficacy on the pancreatic endocrine tissue than some previously described molecules. Lastly, radioisotopic experiments further identified R/ S- N-4-chlorophenyl- N′-(6- tert-butyloxycarbonylamino-3,4-dihydro-2,2-dimethyl-2 H-1-benzopyran-4-yl)thiourea (23) as a K ATP channel opener.

<b>Green and practical synthesis of benzopyran and 3-sunstituted coumarin derivatives by Brønsted acid ionic liquid [(CH<sub>2</sub>)<sub>4</sub>SO<sub>3</sub>HMIM][HSO<sub>4</sub>]</b>

Different benzopyran and 3-substituted coumarin derivatives were synthesized by a green and practical procedure in the presence of catalytic amount of Bronsted acid ionic liquid (BAIL) [(CH 2 ) 4 SO 3 HMIM][HSO 4 ] in water. KEY WORDS : Benzopyran derivatives, 3-Substituted coumarin derivatives, Bronsted acid ionic liquid, 1-(4-Sulfonic acid)butyl-3-methylimidazolium hydrogen sulfate Bull. Chem. Soc. Ethiop. 2011 , 25(2), 315-320.

Glycerol誘発ラット急性腎不全モデルに対するK-channel opener(Y-26763)の予防効果

Y-26763, a benzopyran derivative, is a newly developed ATp-sensitive K channel opener and has been reported to protect against ischemic acute renal failure (ARF). We examined the effects of Y-26763 on glycerol-induced myoglobinuric ARF in the rats. ARf was induced in 28 adult male Sprague-Dawley rats by hind-limb intramuscular injection of 50% glycerol (5 ml/kg) after 18 hrs of water deprivation. Y-26763, 7 micrograms/kg (GY group, n = 10) of vehicle (G group, n = 12) was given intravenously 15 min before glycerol injection. Glibenclamide (20 mg/kg), a K channel blocker was given prior to Y-26763 injection to see of the effects was due to the K-channel opener (GYG group, n = 6). Animals were sacrificed 24 or 96 hrs after glycerol injection. Y-26763 partially, but significantly, restored renal dysfunction 24 hrs after ARF. Pcr (mg/dl) and Ccr (ml/min), respectively were as follows: G group, 5.7 +/- 0.4, 0.015 +/- 0.006; GY group, 4.1 +/- 0.4, 0.061 +/- 0.027 (p < 0.05). These favorable effects were antagonized by glibenclamide (Pcr in GYG group, 5.4 +/- 0.3 mg/dl, p < 0.05). Renal calcium content was not statistically significant (3.5 +/- 1.2 vs. 3.4 +/- 1.2 micrograms/mg dry weight). Histological examinations revealed that extensive tubular necrosis and cast formation seen in the G group were reduced in the GY group. At the recovery phase, 96 hrs after glycerol injection, Y-26763 accelerated the recovery from ARF as shown in Pcr (mg/dl) and Ccr (ml/min): 4.3 +/- 0.2, 0.05 +/- 0.01 in the G group, 2.8 +/- 0.2, 0.13 +/- 0.02) in the GY group (p < 0.01). In conclusion, Y-26763 partially protected against glycerol-induced ARF.

Acaricidal properties of the essential oil and precocene II obtained from Calea serrata (Asteraceae) on the cattle tick Rhipicephalus ( Boophilus) microplus (Acari: Ixodidae)

Calea serrata Less. (Asteraceae), an endemic species of south Brazil known as “quebra-tudo”, is used in Afro-Brazilian religious rituals and in folk medicine for treating liver disorders. Phytochemical studies of the n-hexane extract of this plant demonstrated the presence of precocene II, a benzopyran derivative known for its insecticidal activity. The aim of this work was to isolate this benzopyran and determine the chemical composition of the essential oil of C. serrata and further to evaluate the acaricidal activity of the essential oil and precocene II against the larvae of Rhipicephalus ( Boophilus) microplus. The LC 99.9 and LC 50 values obtained with the oil, which presents precocene II and sesquiterpenes, were 3.94 μL/mL and 0.28 μL/mL, respectively. For precocene II this values were 4.25 mg/mL and 1.78 mg/mL, respectively. The results indicate a synergistic interaction between the components of the oil and precocene II.

ChemInform Abstract: Palladium‐Catalyzed [4 + 2] Cycloaddition of o‐(Silylmethyl)benzyl Esters with Ketones: An Equivalent to Oxo‐Diels—Alder Reaction of o‐Xylylenes.

AbstractThe procedure affords various benzopyran derivatives where the regioselectivity depends on the structure of both substrates (reaction mechanism).

ChemInform Abstract: Catalytic Asymmetric Intramolecular Cascade Reaction for the Construction of Functionalized Benzobicyclo[4.3.0] Skeletons. Remote Control of Enantioselectivity.

AbstractCyclopenta‐fused benzopyran and naphthalene derivatives are prepared using a spirobiindane‐based chiral phosphine as catalyst.

RETRACTION NOTICE: Molecular Transformation of 2, 6-Xylenol to Benzopyran Derivatives from Reaction of Oxaruthenacycle Complex with Dimethyl Acetylenedicarboxylate

RETRACTION NOTICE: Molecular Transformation of 2, 6-Xylenol to Benzopyran Derivatives from Reaction of Oxaruthenacycle Complex with Dimethyl Acetylenedicarboxylate

Catalytic Performance of Heteropolyacids as Efficient and Eco-Friendly Catalysts for the One-Pot Synthesis of Benzopyran Derivatives

An efficient and improved procedure for the synthesis of benzopyran derivatives has been achieved with Keggin-type and Preyssler-type heteropolyacids (HPA) catalysts in one-pot reaction under solvent-free conditions.

Two new benzopyran derivatives from Gouania leptostachya DC. var. tonkinensis Pitard.

Abstract Two new benzopyran derivatives, 1-[(rel 2S,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]ethanone (1), and 1-[(rel 2S,3S)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]ethanone (2), along with four known flavonoids, prodelphinidin C, prodelphinidin B3, (−)-epi-gallocatechin and (+)-gallocatechin, were isolated from the stems of Gouania leptostachya DC. var. tonkinensis Pitard. Their structures were determined on the basis of spectroscopic methods including HR-ESI-MS, 1D and 2D NMR. Prodelphinidin C exhibited significant inhibitory activity for α-glucosidase.

Efficient one-pot synthesis of 1,3-diaryl-3H-benzo[f]chromenes using ferric hydrogensulfate

Abstract An efficient and easy method for one-pot three-component synthesis of 1,3-disubstituted-3H-benzo[f]chromenes by the condensation of naphtol, aromatic aldehyde derivatives and phenylacetylene in the presence of ferric hydrogensulfate [Fe(HSO4)3], has been described. The catalyst displayed high activity which afforded the corresponding 1,3-disubstituted-3H-benzo[f]chromenes in satisfying yields. Alkyl-substituted phenols were examined and the corresponding benzopyran derivatives were synthesized in moderate yields. Heterogeneous nature of the using catalyst made it reusable for further chemical reactions.

A Novel Synthesis of Acetophenone Benzopyran Derivative

The development of a novel synthesis of acetophenone benzopyran is reported. A acetophenone benzopyran derivative was prepared from 1-(2,4-dihydroxyphenyl)ethanone (3) through O-prenylation and Lewis acids catalyzed intermolecular cyclization reaction. The structure of product 1-(3,4-dihydro-4,4-dimethyl-7-hydroxy-2H-1- benzopyran -6-yl)- ethanone (1) was characterized by UV, IR, 1H-NMR, 13C-NMR and elemental analysis.

Melanoma skin cancer: could chromone derivatives be efficient chemopreventors?

Melanoma is a highly metastatic tumour and its incidence has ranked 5th and 6th among the most common cancer afflicting both men and women. Melanoma cells have a diminished antioxidant potential compared to normal melanocytes, which leads to an accumulation of ROS [1]. 1,4-benzopyrone heterocyclic compounds are widely distributed in plants and are reported to exhibit several biological roles, including antioxidant and free radical scavenging [2], displaying a variety of pharmacological properties such as anti-inflammatory and antitumour [3]. The present study aimed to assess the response of the melanotic human skin melanoma (A375) cell line to treatment with 8 different benzopyran derivatives (eg. fisetin, luteolin and quercetin) - in the concentration range 12.5 - 100µM, for 24, 48 and 72h incubation periods (using the MTT assay). Reversibility of the drug effect (after 3 days) was also tested. Concomitantly, similar experiments were carried out for non-neoplasic, non-immortalised, human foreskin fibroblasts (BJ). The results thus gathered allowed to conclude that the chromone derivatives are promising chemopreventive and/or chemotherapeutic agents towards melanoma, while having no considerable adverse effect against healthy cells.

ChemInform Abstract: Synthesis of Benzopyran Derivatives. Part 19. On the Synthesis of Substituted 2,2-Dimethyl-4-chromanones and Related Compounds.

ChemInform Abstract: Synthesis of Benzopyran Derivatives. Part 19. On the Synthesis of Substituted 2,2-Dimethyl-4-chromanones and Related Compounds.

Design, Synthesis and Biological Evaluation of Benzopyran Derivatives as KATP Channel Openers

In order to complete the SAR and discover new potent and selective PCOs, some changes were made to the C-4 and C-2 substitutions of cromakalim. A series of 4 -amino acid substituted -2, 2-dialkylchromans structurally related to cromakalim were synthesized and evaluated, as ATP-sensitive potassium channel openers (8a-l). Preliminary biological tests suggested that these compounds exhibited potent to mild relaxation activity of the KCl-contracted rat aortic strips. Compounds 8b (IC50 =0.25μM), 8f (IC50 =6.44μM) and 8j (IC50 =8.65μM) exhibited commendable opening activity of potassium channels. In addition to anti-hypertension, these compounds can also be considered as lead candidates for the further development of myocardial antiischemic drugs. Keywords: Anti-hypertension, KATP Channel Openers, Benzopyran derivatives, Synthesis