Evaluation of Biological Activity Exerted by Dibenzo[b,e]Thiophene-11(6H)-One on Left Ventricular Pressure Using an Isolated Rat Heart Model

Abstract

Background Some studies show that some Dibenzo derivatives can produce changes in the cardiovascular system; however, its molecular mechanism is not very clear.

Objective The objective of this investigation was to evaluate the inotropic activity of ten Dibenzo derivatives (compounds 1 to 10) on either perfusion pressure or left ventricular pressure.

Methods Biological activity produced by the Dibenzo derivatives on either perfusion pressure or coronary resistance was evaluated using an isolated rat heart. In addition, the molecular mechanism of biological activity produced by compound 4 (Dibenzo[b,e]thiophene-11(6H)-one) on left ventricular pressure was determined using both Bay-k8644 and nifedipine as pharmacological tools in an isolated rat heart model.

Results The results showed that Dibenzo[b,e]thiophene-11(6H)-one increases perfusion pressure and coronary resistance at a dose of 0.001 nM. Besides, other data display that Dibenzo[b,e]thiophene-11(6H)-one increases left ventricular pressure in a dose-dependent manner (0.001 to 100 nM) and this effect was similar to biological activity produced by Bay-k8644 drug on left ventricular pressure. However, the effect exerted by Dibenzo[b,e]thiophene-11(6H)-one was inhibited in the presence of nifedipine at a dose of 1 nM.

Conclusions All these data suggest that Dibenzo[b,e]thiophene-11(6H)-one increase left ventricular pressure through calcium channel activation. In this way, Dibenzo[b,e]thiophene-11(6H)-one could be a good candidate as positive inotropic agent to heart failure.

Key words

Dibenzo - derivative - calcium - channel

Publication History

Received: 17 November 2022

Accepted: 06 December 2022

Article published online:
01 March 2023

• References

• 1 Wang X, Zhang C. Chinese Expert Consensus on the Diagnosis and Treatment of Chronic Heart Failure in Elderly Patients. Aging Med 2022; 5: 78-93
• 2 Sciacqua A, Succurro E, Armentaro G. et al. Pharmacological treatment of type 2 diabetes in elderly patients with heart failure: randomized trials and beyond. Heart Fail Rev 2021; 1: 1-15
• 3 Hirose S, Matsue Y, Kamiya K. et al. Prevalence and prognostic implications of malnutrition as defined by GLIM criteria in elderly patients with heart failure. Clin Nut 2021; 40: 4334-4340
• 4 Katano S, Yano T, Kouzu H. et al. Energy intake during hospital stay predicts all-cause mortality after discharge independently of nutritional status in elderly heart failure patients. Clin Res Cardiol 2021; 110: 1202-1220
• 5 Collard C, Gelman S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. J Ame Soc Anesth 2001; 94: 1133-1138
• 6 Yellon D, Hausenloy D. Myocardial reperfusion injury. New Engl J Med 2007; 357: 1121-1135
• 7 Van't Hof A, Liem A, Suryapranata H. et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Circulation 1998; 97: 2302-2306
• 8 Verma S, Fedak P, Weisel R. et al. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation 2002; 105: 2332-2336
• 9 Van-Deursen V, Hernandez A, Stebbins A. et al. Nesiritide, renal function, and associated outcomes during hospitalization for acute decompensated heart failure: results from the Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure. Circulation 2014; 130: 958-965
• 10 Amar M, Lam S, Faulkenberg K. et al. Captopril Versus Hydralazine-Isosorbide Dinitrate Vasodilator Protocols in Patients With Acute Decompensated Heart Failure Transitioning From Sodium Nitroprusside. J Cardiac Fail 2021; 27: 1053-1060
• 11 Hiebert B, Janzen B, Sanjanwala R. et al. Impact of spironolactone exposure on prostate cancer incidence amongst men with heart failure: A Pharmacoepidemiological study. British. J Clin Pharm 2021; 87: 1801-1813
• 12 Shah P, Pellicori P, Hanning I. et al. The effect of digoxin on renal function in patients with heart failure. BMC Nephrol 2021; 22: 1-9
• 13 Mathew R, Di-Santo P, Jung R. et al. Milrinone as compared with dobutamine in the treatment of cardiogenic shock. New Eng J Med 2021; 385: 516-525
• 14 Franco R, De-Almeida J, Landoni G. et al. Dobutamine-sparing versus dobutamine-to-all strategy in cardiac surgery: a randomized noninferiority trial. Ann Int Care 2021; 11: 1-9
• 15 Liu D, Ning Y, Lei Y. et al. Levosimendan versus dobutamine for sepsis-induced cardiac dysfunction: a systematic review and meta-analysis. Sci Rep 2021; 11: 1-12
• 16 Ziff O, Kotecha D. Digoxin: The good and the bad. Trends Cardiovas Med 2016; 26: 585-595
• 17 Mertes H, Sawada S, Ryan T. et al. Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography. Experience in 1118 patients. Circulation 1993; 88: 15-19
• 18 Barnwal N, Umbarkar S, Sarkar M. et al. Randomized comparative study of intravenous infusion of three different fixed doses of milrinone in pediatric patients with pulmonary hypertension undergoing open heart surgery. Ann Cardiac Anaesth 2017; 20: 318
• 19 Melero C, Sevillano L, Caballero E. et al. Hydroindenic-guanylhydrazones. Synthesis and evaluation as inotropic agents. Bioorg Med Chem Lett 1998; 8: 3217-3222
• 20 Press J, Falotico R, Hajos Z. et al. Synthesis and structure-activity relationship of 6-substituted purine derivatives as novel selective positive inotropes. J Med Chem 1992; 35: 4509-4515
• 21 Thomas R, Roth-Schechter B, Okita G. et al. Synthesis and positive inotropic effect of strophanthidol 3-bromoacetate-19-3H. J Med Chem 1970; 13: 357-359
• 22 Zhang C, Cui X, Hong L. et al. Synthesis and positive inotropic activity of N-(4, 5-dihydro-[1, 2, 4] triazolo [4, 3-a] quinolin-7-yl)-2-(piperazin-1-yl) acetamide derivatives. Bioorg Med Chem Lett 2008; 18: 4606-4609
• 23 Foss A, Boggia R, Presti E. et al. Inotropic agents. Synthesis and structure-activity relationships of new milrinone related cAMP PDE III inhibitors. Farmaco 1997; 52: 523-530
• 24 Kumar R, Yadav N, Lavilla R. et al. Synthesis, pharmacological evaluation and molecular docking of pyranopyrazole-linked 1, 4-dihydropyridines as potent positive inotropes. Mol Div 2017; 21: 533-546
• 25 Figueroa-Valverde L, Lopez-Ramos F, Rosas-nexticapa M. et al. Synthesis and Biological Activity of the Pyridine-hexacyclic-steroid Derivative on a Heart Failure Model. Anti-Inflam Anti-All Agents Med Chem 2022; 21: 34-45
• 26 Statistical
• 27 Lagunin A, Zakharov A, Filimonov D. et al. QSAR modelling of rat acute toxicity on the basis of PASS prediction. Mol Inf 2011; 30: 241-250
• 28 Mvondo J, Matondo A, Mawete D. et al. In Silico ADME/T Properties of Quinine Derivatives using SwissADME and pkCSM Webservers. Int J Trop Dis Health 2021; 42: 1-12
• 29 Poppe H, Kaverina N, Lyskovzev V. et al. New 5-aminoacyl-5, 10-dihydro-11H-dibenzo [b, e][1, 4] diazepin-11-ones with antiarrhythmic activity. Die Pharm 2011; 52: 821-830
• 30 Yim T, Ko K. Methylenedioxy group and cyclooctadiene ring as structural determinants of schisandrin in protecting against myocardial ischemia-reperfusion injury in rats. Biochem Pharmacol 1999; 57: 77-81
• 31 Dohmoto H, Takahara A, Uneyama H. et al. Cardiac Ca2+channel-blocking effects of the cyproheptadine derivative AH-1058 in isolated guinea pig cardiomyocytes. J Pharmacol Sci 2003; 91: 163-166
• 32 Figueroa-Valverde L, Diaz-Cedillo F, Lopez-Ramos M. et al. Changes induced by estradiol-ethylenediamine derivative on perfusion pressure and coronary resistance in isolated rat heart: L-type calcium channel. Biomed Pap 2011; 155: 27-32
• 33 López-Ramos M, Figueroa-Valverde L, Herrera-Meza S. et al. Design and synthesis of a new steroid-macrocyclic derivative with biological activity. J Chem Biol 2017; 10: 69-84
• 34 Thoenen H, Huerlimann A, Haefely W. Mode of action of imipramine and 5-(3’-methylaminopropyliden)dibenzo[a,e]cyclohepta[1.3.5]trien hydrochloride (RO 4-6011), a new antidepresant drug, on peripheral adrenergic mechanism. J Pharm Exp Ther 1964; 144: 405-414
• 35 Hitomi M, Kumadaki N, Furukawa T. et al. Pharmacological study of piroheptine, a new antiparkinson drug, 3-(10, 11-dihydro-5H-dibenzo (a, d) cyclohepten-5-ylidene)-1-ethyl-2-methylpyrrolidine. I. Effects on drug-induced tremor and catatonia, and on adrenergic actions. Arzneimittel-Forschung 1972; 22: 953-961
• 36 Clineschmidt B, McKendry M, Papp P. et al. Stereospecific antidopaminergic and anticholinergic actions of the enantiomers of (+/-)-1-cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo [a, d] cyclohepten-5-ylidene) piperidine (CTC), a derivative of cyproheptadine. J Pharmacol Exp Ther 1979; 208: 460-467
• 37 Memetzidis G, Stambach J, Jung L. et al. Structure-affinity relationships of berbines or 5, 6, 13, 13a-tetrahydro-8H-dibenzo [a, g] quinolizines at α-adrenoceptors. Eur J Med Chem 1991; 26: 605-611
• 38 Rose L, Graham L, Koenecke A. et al. The association between alpha-1 adrenergic receptor antagonists and in-hospital mortality from COVID-19. Front Med 2021; 8: 637647
• 39 Garcia P, Montastruc J, Rousseau V. et al. β-adrenoceptor antagonists and nightmares: A pharmacoepidemiological–pharmacodynamic study. J Psychopharm 2021; 35: 1441-1448
• 40 McFarlane C, Piechuta H, Hall R, Ford-Hutchinson A. Effects of a contractile prostaglandin antagonist (L-640, 035) upon allergen-induced bronchoconstriction in hyperreactive rats and conscious squirrel monkeys. Prostaglandins 1984; 28: 173-182
• 41 Carlson R, Datko L, Chang J. et al. The antiinflammatory profile of (5H-dibenzo [A, D]-cyclohepten-5-ylidene) acetic acid (WY-41,770), an agent possessing weak prostaglandin synthetase inhibitory activity that is devoid of gastric side effects. Ags Act 1984; 14: 654-661
• 42 Hall R, Rokach J, Belanger P. et al. L-641,953 (R-8-fluoro-dibenzo [b, f] thiepin-3-carboxylic acid-5-oxide): a novel thromboxane–prostaglandin endoperoxide antagonist. Canadian J Physiol Pharmacol 1987; 65: 509-514
• 43 Ito A, Mori Y. Effect of a novel anti-inflammatory drug, 2-(10, 11-dihydro-10-oxo-dibenzo [b, f]-thiepin-2-yl) propionic acid (CN-100), on the proteoglycan biosynthesis in articular chondrocytes and prostaglandin E2 production in synovial fibroblasts. Res Comm Chem Pathol Pharmacol 1990; 70: 131–142
• 44 Villar-Martínez M, Moreno-Ajona D, Chan C. et al. Indomethacin-responsive headaches-A narrative review. J Head d Face Pain 2021; 61: 700-714
• 45 Nonnenmacher E, Hever A, Mahamoud A. et al. A novel route to new dibenzo [b, f][1, 5] diazocine derivatives as chemosensitizers. Org Prep Proc Int 1997; 29: 711-715
• 46 Li R, Farmer P, Quillam M. et al. Dibenzothiazepinones as potential calcium channel antagonists. I. Drug Des Dis 1993; 10: 331-342
• 47 Schramm M, Thomas G, Towart R. et al. Novel dihydropyridines with positive inotropic action through activation of Ca²⁺channels. Nature 1983; 303: 535-537
• 48 Lauro F, Francisco D, Marcela R. et al. Synthesis and biological activity of two oxireno-azecin-imidazole derivatives on perfusion pressure via guanylate cyclase inhibition. Biointer Res Appl Chem 2018; 3543-3551
• 49 Lauro F, Maria L, Francisco D. et al. Synthesis and Biological Activity of the Pyridine-hexacyclic-steroid Derivative on a Heart Failure Model. Anti-Inflam Anti-Aller Agents Med Chem 2022; 21: 34-45
• 50 Manohar K, Gupta R, Gupta P. et al. FDA approved L-type channel blocker Nifedipine reduces cell death in hypoxic A549 cells through modulation of mitochondrial calcium and superoxide generation. Free Radical Biol Med 2021; 177: 189-200
• 51 Vicente M, Salgado-Almario J, Collins M et al. Cardioluminescence in transgenic zebrafish larvae: a calcium imaging tool to study drug effects and pathological modeling. Biomed 20221; 9: 1294
• 52 Duan H, Wu C, Shen S. et al. Neuroprotective effects of early brain injury after subarachnoid hemorrhage in rats by calcium channel mediating hydrogen sulfide. Cell Mol Neurobiol 2021; 41: 1707-1714
• 53 Figueroa-Valverde L, Rosas-Nexticapa M, Montserrat M et al. Synthesis and Theoretical Interaction of 3-(2-oxabicyclo [7.4. 0] trideca-1 (13), 9, 11-trien-7-yn-12-yloxy)-steroid Deriva-tive with 17β-hydroxysteroid Dehydrogenase Enzyme Surface. Bioint Res Appl Chem 2023; 13, 266 on line
• 54 Damonte P, Sociali G, Parenti M. et al. SIRT6 inhibitors with salicylate-like structure show immunosuppressive and chemosensitizing effects. Bioorg Med Chem 2017; 25: 5849-5858
• 55 Keizer R, Karlsson M, Hooker A. Modeling and simulation workbench for NONMEM: tutorial on Pirana, PsN, and Xpose. Pharmacom Syst Pharmacol 2013; 2: 1-9
• 56 Figueroa-Valverde L, Diz-Cedillo F, Gobato R. et al. Design and synthesis of two Strychnidin-oxiran-naphthalenol derivatives and their theoretical evaluation as noradrenaline and serotonin reuptake inhibitors. Vietnam J Chem 2022; 60: 245-256