The Antiallergic Activities of Synthetic Acrophylline and Acrophyllidine

Huang, An‐Cheng; Lin, Tsung-Ping; Kuo, Sheng‐Chu; Wang, Jih-Pyang

doi:10.1021/np50115a016

Cited by 8 publications

(6 citation statements)

References 6 publications

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“…Moreover, ethyl 2-[N-m-chlorobenzyl-(2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01006) induced the increase in ROS production that resulted in the caspase-dependent apoptosis of human cervical cancer cells (13). In addition to anticancer activity, the intermediates of furoquinoline synthesis and furoquinoline derivatives have been revealed to exhibit diverse pharmacological effects, such as 5-HT2 receptor antagonist activity (24), vasorelaxation via the suppression of calcium influx (25), anti-allergic effects (9) and the blocking of outward K + current and Na + channels (5). A previous study revealed that the intermediates of furoquinoline synthesis exhibited moderate inhibitory effects on the growth of human ovarian cancer A2780 cells (26).…”

Section: Discussionmentioning

confidence: 99%

“…Acrophylline and acrophyllidine have structures that are similar to furoquinolone, and can be isolated from Acronychia, Dictamnus, Ptelea, Glycosmis and Ruta plants (6), which exhibit antimicrobial and anticancer activities (7,8). Acrophyllidine and its synthetic derivatives also exhibit significant anti-allergic activity via suppressing mast cell degranulation (9). Moreover, ethyl 2-(3-hydroxyanilino)-4-oxo-4,5-dihydrofuran-3-carboxylate, an intermediate in furoquinolone synthesis, exhibits anti-inflammatory activity (10) and ethyl 2-[N-p-chlorobenzyl-(2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01007) has also been revealed to induce apoptosis in mouse leukemia (WEHI-3) and human cervical cancer (CaSki) cell lines (11,12).…”

Section: Introductionmentioning

confidence: 99%

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Ethyl 2‑anilino‑4‑oxo‑4,5‑dihydrofuran‑3‑carboxylate exhibits anti‑proliferative activity and induces apoptosis in promyelocytic leukemia HL‑60 cells

Huang¹,

Lin

Lien

et al. 2020

Oncol Lett

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Furoquinolone and its derivatives exhibit antimicrobial, anti-allergic, anti-inflammatory and anticancer properties. The present study investigated the anti-tumor activity of synthesized intermediates of furoquinolone in human promyelocytic leukemia HL-60 cells. The biological effects of the active compound ethyl 2-anilino-4-oxo-4,5dihydrofuran-3-carboxylate (compound 131) were examined in HL-60 cells. The following properties were analyzed: Cell survival, cell cycle profile, caspase-3 activity, Bax and Bcl-2 expression, the amount of intracellular Ca 2+ , the number of reactive oxygen species (ROS) and the mitochondrial membrane potential. Compound 131 (50% cytotoxic concentration , 23.5 µM) significantly reduced the proliferation of HL-60 cells and was revealed to induce apoptosis in HL-60 cells in a concentration-dependent manner. Moreover, this was associated with the activation of caspase-3, upregulation of Bax, an increase in intracellular Ca 2+ and ROS production, and a decrease in mitochondrial membrane potential and Bcl-2 expression levels. Compound 131, a novel 4,5-dihydrofuran-3-carboxylate, induced apoptosis in HL-60 cells via the increase of intracellular Ca 2+ and ROS to alter the mitochondrial membrane potential and the protein level of Bax and Bcl-2, as well as activating caspase-3. The results of the current study indicate that compound 131 may represent a promising compound for the development of anti-leukemia therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ethyl 2‑anilino‑4‑oxo‑4,5‑dihydrofuran‑3‑carboxylate exhibits anti‑proliferative activity and induces apoptosis in promyelocytic leukemia HL‑60 cells

Huang¹,

Lin

Lien

et al. 2020

Oncol Lett

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“…The Cs + -containing pipette solution contained (in mM) CsCl 130.0, EGTA 5.0, tetraethylammonium (TEA) chloride 15.0, dextrose 5.0, and HEPES 10.0, adjusted to pH 7.2 with CsOH. Acrophyllidine was synthesized by Dr. S.C. Kuo as previously described [Huang et al, 1995]. Its purity (>99%) was confirmed by spectral methods (mass and NMR).…”

Section: Solutions and Compoundsmentioning

confidence: 99%

“…Skimmianine and kokusaginine (isolated from Evodia merrilli) are selective 5-HT 2 receptor antagonists [Cheng et al, 1994]. Acrophylline and acrophyllidine, another two furoquinolines isolated from the plant Acronychia halophylla [Lahey and McCamish, 1968], possess potent antiallergic activity [Huang et al, 1995]. Recently, by using large-scale screening tests, acrophyllidine ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological characteristics of antiarrhythmic potential of acrophyllidine, a furoquinoline alkaloid isolated fromAcronychia halophylla

Chang

Chen

et al. 2000

Drug Dev. Res.

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The antiarrhythmic potential of acrophyllidine, a natural furoquinoline alkaloid isolated from the plant, Acronychia halophylla, has been documented. In the present study, the electrophysiological effects of acrophyllidine in Langendorff‐perfused rat hearts and isolated cardiomyocytes were examined. In isolated rat heart (constant pressure), acrophyllidine suppressed ischemia/reperfusion‐induced polymorphic ventricular tachyarrhythmias with an EC50 value of 4.4 μM. In the perfused whole‐heart model (constant flow), acrophyllidine increased the atrioventricular and His‐Purkinje system conduction intervals, ventricular repolarization time (VRT), and basic cycle length and also prolonged the refractory periods of the AV node, His‐Purkinje system and ventricle. In isolated rat ventricular myocytes, acrophyllidine prolonged the action potential duration (APD) and decreased both the maximal upstroke velocity of depolarization (Vmax) and action potential amplitude in a concentration‐dependent manner. Whole‐cell voltage clamp studies show that acrophyllidine blocked the Na+ channel (IC50 = 3.6 μM) with a negative‐shift of its voltage‐dependent steady‐state inactivation curve and slowing of its recovery from inactivation. Similarly, Ca2+ inward current (ICa) was inhibited but to a lesser extent. Acrophyllidine also suppressed the transient outward (Ito) (IC50 equals; 4.5 μM) and the steady‐state outward K+ current (ISS) (IC50 = 3.4 μM). The inhibition of Ito was associated with an acceleration of its rate of inactivation. Additionally, acrophyllidine suppressed Ito in a time‐dependent manner and caused a negative‐shift of the steady‐state inactivation curve and a slowed rate of recovery from inactivation. It is concluded that acrophyllidine blocks Na+, Ito and ISS channels and in similar concentrations partly blocks Ca2+ channel. These changes alter the electrophysiological properties of the conduction system and may be responsible for the termination of the ischaemia/reperfusion induced ventricular arrhythmias. Drug Dev. Res. 50:170–185, 2000. © 2000 Wiley‐Liss, Inc.

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“…Skimmianine and kokusaginine (isolated from Evodia merrillii) were found to have selective 5-HT 2 receptor antagonistic activity (Cheng et al, 1994). Acrophylline and acrophyllidine, another two furoquinolines isolated from Acronychia halophylla, were demonstrated to possess signi®cant antiallergic activity (Huang et al, 1995). Recently, in a large scale screening test, we found that HA-7 (Figure 1a), a newly synthesized furoquinoline derivative, can increase the contractile force in isolated rat ventricular strips (Figure 1b and c).…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological basis for the antiarrhythmic action and positive inotropy of HA‐7, a furoquinoline alkaloid derivative, in rat heart

Chang

et al. 1997

British J Pharmacology

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1 HA-7, a new synthetic derivative of furoquinoline alkaloid, increased the contractile force of right ventricular strips and eectively suppressed the ischaemia-reperfusion induced polymorphic ventricular tachyrhythmias in adult rat heart (EC 50 =2.8 mM). 2 In rat ventricular myocytes, HA-7 concentration-dependently prolonged the action potential duration (APD) and decreased the maximal rate of rise of the action potential upstroke (V . max ). The action potential amplitude and resting membrane potential were also reduced, but to a smaller extent. The prolongation of APD by HA-7 was prevented by pretreating the cells with 1 mM 4-AP. 3 Voltage clamp experiments revealed that HA-7 decreased the maximal current amplitude of I Na (IC 50 =4.1 mM) and caused a negative shift of its steady-state inactivation curve and slowed its rate of recovery from inactivation. The use-dependent inhibition of I Na by HA-7 was enhanced at a higher stimulation rate. The L-type Ca 2+ current (I Ca ) was also reduced, but to a lesser degree (IC 50 =5.3 mM, maximal inhibition=31.8%). 4 This agent also in¯uenced the time-and voltage-dependent K + currents. The prolongation of APD was associated with an inhibition of a 4-AP sensitive transient outward K + current (I to ) (IC 50 =2.9 mM) and a slowly inactivating, steady-state outward current (I ss ) (IC 50 =2.5 mM). The inhibition of I to by HA-7 was associated with an acceleration of its time constant of inactivation. HA-7 suppressed I to in a time-dependent manner and caused a signi®cant negative shift of the voltage-dependent steady-state inactivation curve but did not aect its rate of recovery from inactivation. 5 At higher concentrations, the inward recti®er K + current (I K1 ) was also inhibited but to a less extent. Its slope conductance after 3, 10 and 30 mM HA-7 was decreased by 24+4%, 41+5% and 54+8%, respectively. 6 We conclude that HA-7 predominantly blocks I to and Na + channels and that it also weakly blocks Ca 2+ and I K1 channels. These changes alter the electrophysiological properties of the heart and terminate the ischaemia reperfusion induced ventricular arrhythmia. The signi®cant I to inhibition and minimal I Ca suppression may aord an opportunity to develop an eective antiarrhythmic agent linked with positive inotropy.

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The Antiallergic Activities of Synthetic Acrophylline and Acrophyllidine

Cited by 8 publications

References 6 publications

Ethyl 2‑anilino‑4‑oxo‑4,5‑dihydrofuran‑3‑carboxylate exhibits anti‑proliferative activity and induces apoptosis in promyelocytic leukemia HL‑60 cells

Ethyl 2‑anilino‑4‑oxo‑4,5‑dihydrofuran‑3‑carboxylate exhibits anti‑proliferative activity and induces apoptosis in promyelocytic leukemia HL‑60 cells

Electrophysiological characteristics of antiarrhythmic potential of acrophyllidine, a furoquinoline alkaloid isolated fromAcronychia halophylla

Electrophysiological basis for the antiarrhythmic action and positive inotropy of HA‐7, a furoquinoline alkaloid derivative, in rat heart

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