W. Abdallah, M. Znati, A. Regazzetti, D. Dargère, O. Laprévote et al., Synthesis of S-mono-and S,O-bis-1,2,3-triazole linked 1,5-benzodiazepine conjugates and evaluation of their cytotoxic, anti-tyrosinase, and anti-cholinesterase activities. Phosphorus, Sulfur Silicon Relat. Elem, vol.192, pp.835-844, 2017.

A. M. Abbas, Cardioprotective effect of resveratrol analogue isorhapontigenin versus omega-3 fatty acids in isoproterenol-induced myocardial infarction in rats, J. Physiol. Biochem, vol.72, pp.469-484, 2016.

H. Ahsan, A. Ahad, J. Iqbal, and W. A. Siddiqui, Pharmacological potential of tocotrienols: A review, Nutrition Metabol, vol.11, pp.52-74, 2014.

R. Anandan, S. Mathew, T. V. Sankar, and N. P. Viswanathan, Protective effect of n-3 polyunsaturated fatty acids concentrate on isoproterenol induced myocardial infarction in rats, 2007.

, Prostaglandins Leukot Essent. Fatty Acids, vol.76, pp.153-158

D. M. Attalla, L. A. Ahmed, H. F. Zaki, and M. M. Khattab, Paradoxical effects of atorvastatin in isoproterenol-induced cardiotoxicity in rats: Role of oxidative stress and inflammation, 2018.

, Biomedicine & Pharmacotherapy, vol.104, pp.542-549

E. J. Benjamin, M. J. Blaha, S. E. Chiuve, M. Cushman, S. R. Das et al., Heart disease and stroke statistics 2017 up-date: a report from the, American Heart Association. Circulation, vol.135, issue.10, pp.146-603, 2017.

R. C. Braga, V. M. Alves, C. A. Fraga, E. J. Barreiro, V. De-oliveira et al., Combination of docking, molecular dynamics and quantum mechanical calculations for metabolism prediction of 3,4-methylenedioxybenzoyl-2-thienylhydrazone, J Mol Model, vol.18, pp.2065-2078, 2012.

W. A. Border and N. A. Noble, Transforming growth factor ? in tissue fibrosis, New Eng. J. Med, vol.331, pp.1286-1292, 1994.

C. Borghi, S. Bacchelli, D. D. Esposti, and E. Ambrosioni, Effects of early angiotensinconverting enzyme inhibition in patients with non-ST-elevation acute anterior myocardial infarction, Amer. Heart J, vol.152, pp.470-477, 2006.

S. Chekir, M. Debbabi, A. Regazzetti, D. Dargère, O. Laprévote et al., Design, synthesis and biological evaluation of novel 1,2,3-triazole linked coumarinopyrazole conjugates as potent anti-cholinesterase, anti-5-lipoxygenase, anti-tyrosinase and anti-cancer agents, Bioorg. Chem, vol.80, pp.189-194, 2018.

H. Chen, S. Li, Y. Yao, L. Zhou, J. Zhao et al., Design, synthesis, and anti-tumor activities of novel triphenylethylene-coumarin hybrids, and their interactions with Ct-DNA, Bioorg. Med. Chem. Lett, vol.23, pp.4785-4789, 2013.

R. C. Chelucci, L. A. Dutra, M. E. Lopes-pires, T. R. De-melo, P. L. Bosquesi et al., Antiplatelet and Antithrombotic Activities of non-steroidal anti-inflammatory drugs containing an N-acyl hydrazone subunit, Molecules, vol.19, pp.2089-2099, 2014.

A. Clauss, Rapid physiological coagulation method in determination of fibrinogen, Acta Haematol, vol.17, pp.237-246, 1957.

I. Conti, R. Morigi, A. Locatelli, M. Rambaldi, G. Bua et al., Synthesis of 3-(imidazo[2,1-b]thiazol-6-yl)-2H-chromen-2-one derivatives and study of their antiviral activity against parvovirus B19, Molecules, vol.24, pp.1037-1052, 2019.

J. Danesh, S. Lewington, S. G. Thompson, G. D. Lowe, R. Collins et al., Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis, J Am. Med. Asso, vol.294, pp.1799-1809, 2005.

A. Daoud, K. Mnafgui, M. Turki, S. Jmal, F. Ayadi et al., Cardiopreventive effect of ethanolic extract of Date Palm Pollen against isoproterenol induced myocardial infarction in rats through the inhibition of the angiotensin-converting enzyme, Exp. Toxicol. Pathol, vol.69, pp.656-665, 2017.

F. Destaing, Determination of fibrinogen by the Von Clauss coagulation micromethod, Pathol Biol, vol.8, pp.1615-1621, 1960.

Z. Dong, H. Shi, S. Chen, H. Chen, W. Jiang et al., Synthesis of 1,5-benzodiazepine derivatives containing 1,2,3-triazole moiety via 1,3-dipolar cycloaddition reaction, J. Hetero. Chem, vol.51, pp.1844-1848, 2014.

A. Y. Ershov, I. V. Lagoda, S. I. Yakimovich, V. V. Pakalnis, I. V. Zerova et al., Tautomerism and conformational isomerism of mercaptoacetylhydrazones of aliphatic and aromatic aldehydes, Russ. J. Org. Chem, vol.45, pp.660-661, 2009.

R. Elias, R. I. Benhamou, Q. Z. Jaber, O. Dorot, S. L. Zada et al., Antifungal activity, mode of action variability, and subcellular distribution of coumarinbased antifungal azoles, Eur. J. Med. Chem, vol.179, pp.779-790, 2019.

K. C. Fylaktakidou, D. J. Hadjipavlou-litina, K. E. Litinas, and D. N. Nicolaides, Natural and synthetic coumarin derivatives with anti-inflammatory/antioxidant activities, Current Pharm. Design, vol.10, pp.3813-3833, 2014.

I. Filali, M. A. Belkacem, A. B. Nejma, J. P. Souchard, H. B. Jannet et al., Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities of novel derivatives from harmine, J. Enz. Inhib. Med. Chem, vol.31, pp.23-33, 2016.
URL : https://hal.archives-ouvertes.fr/hal-02195504

G. Vigil-de-mello, S. V. Frode, and T. S. , In vitro and in vivo experimental model-based approaches for investigating anti-inflammatory properties of coumarins 25, pp.1446-1476, 2018.

L. Ghazouani, E. Khdhiri, A. Elmufti, A. Feriani, M. Tir et al., Cardioprotective effects of (E)-4-hydroxy-N?-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)benzohydrazide: a newly synthesized coumarin hydrazone against isoproterenol-induced myocardial infarction in a rat model, Can. J. Physiol. Pharmacol, vol.97, pp.989-998, 2019.

C. Glidewell, J. N. Low, J. M. Skakle, and J. L. Wardell, Hydrogen bonding in 2-nitrobenzaldehyde hydrazones and a three-dimensional hydrogen-bonded framework in 3-nitrobenzaldehyde hydrazone, Acta Crysta Sect C: Cryst. Struct. Commun, vol.60, pp.686-689, 2004.

D. T. Gonzaga, F. C. Silva, V. F. Ferreira, J. L. Wardell, and S. M. Wardell, Crystal structures of 1-aryl-1H-and 2-aryl-2H-1,2,3-triazolyl hydrazones, conformational consequences of different classical hydrogen bonds, J. Braz. Chem. Soc, vol.27, pp.2322-2333, 2016.

E. Jameel, T. Umar, J. Kumar, and N. Hoda, Coumarin: A Privileged scaffold for the design and development of antineurodegenerative agents, Chem. Biol. Drug Design, vol.87, pp.21-38, 2016.

R. S. Keri, B. S. , S. Nagaraja, B. M. Santos, and M. A. , Recent progress in the drug development of coumarin derivatives as potent antituberculosis agents, Eur. J. Med. Chem, vol.100, pp.257-269, 2015.

M. I. Khalil, I. Ahmmed, R. Ahmed, E. M. Tanvir, R. Afroz et al., Amelioration of isoproterenol-induced oxidative damage in rat myocardium by Withania somnifera leaf extract, 2015.

, Biomed Res. Internat. Article ID, vol.624159

V. Khan, M. Q. Hassan, M. Akhtar, and A. K. Najmi, Renin inhibition by aliskiren protects rats against isoproterenol induced myocardial infarction, Drug Res (Stuttg), vol.68, pp.139-145, 2018.

G. Kirsch, A. Abdelwahab, and P. Chaimbault, Natural and synthetic coumarins with effects on inflammation, Molecules, vol.21, pp.1322-1335, 2016.

C. Kontogiorgis, O. Nicolotti, G. F. Mangiatordi, M. Tognolini, F. Karalaki et al., Studies on the antiplatelet and antithrombotic profile of anti-inflammatory coumarin derivatives, Journal of Enzyme Inhibition and Medicinal Chemistry, vol.30, pp.925-933, 2015.

J. Kovvuri, B. Nagaraju, C. Ganesh-kumar, K. Sirisha, C. Chandrasekhar et al., Catalyst-free synthesis of pyrazole-aniline linked coumarin derivatives and their antimicrobial evaluation, J. Saudi Chem. Soc, vol.22, pp.665-677, 2018.

I. Kostova, Synthetic and natural coumarins as cytotoxic agents, Curr. Med. Chem. Anticancer Agents, vol.5, pp.29-46, 2005.

E. Knoevenagel, Condensation von malonsäure mit aromatischen aldehyden durch ammoniak und amine, Chem. Ber, vol.31, pp.2596-2619, 1898.

C. M. Leal, S. L. Pereira, A. E. Kümmerle, D. M. Leal, R. Tesch et al., , 2012.

, Eur. J. Med. Chem, vol.55, pp.49-57

K. R. Machlus, J. C. Cardenas, F. C. Church, and A. S. Wolberg, Causal relationship between hyperfibrinogenemia, thrombosis, and resistance to thrombolysis in mice, Blood, vol.117, pp.4953-4963, 2011.

K. Mnafgui, I. Khlif, R. Hajji, F. Derbali, F. Kraiem et al., Preventive effects of oleuropein against cardiac remodeling after cardiac infarction in Wistar rat through inhibiting angiotensin-converting enzyme activity, Toxicol. Mech. Methods, vol.25, pp.538-546, 2015.

K. Mnafgui, R. Hajji, F. Derbali, I. Khlif, F. Kraiem et al., Protective effect of hydroxytyrosol against cardiac remodeling after isoproterenol-induced myocardial infarction in rat, Cardiovascul. Toxicol, vol.16, pp.147-155, 2016.

K. Mnafgui, E. Khdhiri, L. Ghazouani, M. Ncir, Z. Zaafouri et al., Anti-embolic and anti-oxidative effects of a novel (E)-4-amino-N?-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide against isoproterenol and vitamin-K induced ischemic stroke, Archiv. Physiol. Biochem, pp.1-14, 2019.

E. G. Nabel and E. A. Braunwal, Tale of coronary artery disease and myocardial infarction, New Eng. J. Med, vol.366, pp.54-63, 2012.

L. Pari, N. Rajarajeswari, S. Saravanan, and A. Rathinam, Antihyperlipidemic effect of coumarin in experimental type 2 diabetic rats, Biomed. Prevent. Nutri, vol.4, pp.171-176, 2014.

S. Paula, S. Das, E. M. Tanvir, M. S. Hossen, M. Saha et al., Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit against isoproterenol-induced myocardial infarction in rats, Biomed. Pharmacother, vol.94, pp.256-264, 2017.

C. L. Paracatu, L. Zeraik, M. De-carvalho-bertozo, L. De-andrade-bartolomeu, A. et al., Synthesis, antioxidant and anti-inflammatory properties of an apocynin-derived dihydrocoumarin, Mini Rev. Med. Chem, vol.13, pp.93-100, 2017.

P. Patorski, E. Wyrzykiewicz, and G. Bartkowiak, Synthesis and conformational assignment of N-(E)-stilbenyloxymethylenecarbonyl-substituted hydrazones of acetone and ortho-, meta-and para-chloro-(nitro-)benzaldehydes by means of and NMR spectroscopy, J. Spectroscopy, pp.1-12, 2013.

K. Pérez-cruz, M. Moncada-basualto, J. Morales-valenzuela, G. Barriga-gonzález, P. Navarrete-encina et al., Synthesis and antioxidant study of new polyphenolic hybrid-coumarins, Arabian J. Chem, vol.11, pp.525-537, 2018.

F. Pintus, M. J. Matos, S. Vilar, G. Hripcsak, C. Varela et al., New insights into highly potent tyrosinase inhibitors based on 3-heteroarylcoumarins: Anti-melanogenesis and antioxidant activities, and computational molecular modeling studies, Bioorg. Med. Chem, vol.25, pp.1687-1695, 2017.

M. Ramya, B. Anusha, R. I. Monica-anita, and M. Rajadurai, Rapid molecular detection of salmonella typhi and salmonella paratyphi by polymerase chain reaction, Asian J. Microbiol. Biotechnol. Environ. Sci, vol.9, pp.675-677, 2014.

S. G. Sahu, N. Chakraborty, and P. Sarkar, Coal-biomass co-combustion: An overview, Renew. Sustain. Energy Rev, vol.39, pp.575-586, 2014.

G. Saravanan, P. Ponmurugan, M. Sathiyavathi, S. Vadivukkarasi, and S. Sengottuvelu, Cardioprotective activity of Amaranthus viridis Linn: effect on serum marker enzymes, cardiac troponin and antioxidant system in experimental myocardial infarcted rats, Internat. J. Cardiol, vol.165, pp.494-498, 2013.

S. K. Shukla, S. B. Sharma, and U. R. Singh, ?-Adrenoreceptor agonist Isoproterenol alters oxidative status, inflammatory signaling, injury markers and apoptotic cell death in myocardium of rats, Indian J. Clinical Biochem, vol.30, pp.27-34, 2015.

D. Srikrishna, C. Godugu, and P. K. Dubey, A review on pharmacological properties of coumarins, Mini Rev. Med. Chem, vol.18, pp.113-141, 2018.

M. G. Sutton and N. John, Sharpe, left ventricular remodeling after myocardial infarction, Pathophysiol. Ther, vol.101, pp.2981-2988, 2000.

V. Syakaev, S. Podyachev, B. Buzykin, S. Latypov, W. Habicher et al., NMR study of conformation and isomerization of aryl-and hetero arylaldehyde 4-tert butylphenoxyacetylhydrazones, J. Mol. Struct, vol.788, pp.55-62, 2006.

M. Ufer, Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol, Clin. Pharmacokin, vol.44, pp.1227-1246, 2005.

, World Health Organization (WHO) Fact sheet N°290, World Health Statistics, 2011.

J. Wu, R. E. Aluko, and A. D. Muir, Improved method for direct high-performance liquid chromatography assay of angiotensin-converting enzyme-catalyzed reactions, J. Chromato, vol.950, pp.125-130, 2002.

, Values are given as mean ± standard deviation / S.D. for groups of 6 animals each. The values are statistically presented as follows: a P < 0

, 05 significant difference compared to treated rats with isoprotenol (Isop)

, ? Synthesis of new (E)-N'

, ? In vitro tests showed potent inhibition of angiotensine I-converting enzyme (ACE)

, pre-treatment with 1c improved the ECG pattern ? 1c reduced the cardiac dysfunction markers and ameliorated the thrombolytic process, ? In vivo assays (on rats)