Structure-activity relationship of three synthesized benzimidazole-based oligosaccharides in human platelet activation Corrigendum in /10.3892/ijmm.2019.4423

Chang,Yi; Hsu,Wen-Hsien; Yang,Wen-Bin; Jayakumar,Thanasekaran; Lee,Tzu-Yin; Sheu,Joen-Rong; Lu,Wan-Jung; Li,Jiun-Yi

doi:10.3892/ijmm.2017.3133

Structure-activity relationship of three synthesized benzimidazole-based oligosaccharides in human platelet activation

Corrigendum in: /10.3892/ijmm.2019.4423

Authors:
- Yi Chang
- Wen-Hsien Hsu
- Wen-Bin Yang
- Thanasekaran Jayakumar
- Tzu-Yin Lee
- Joen-Rong Sheu
- Wan-Jung Lu
- Jiun-Yi Li
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Affiliations: Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan, R.O.C., School of Medicine, Fu-Jen Catholic University, Xin Zhuang, New Taipei City 242, Taiwan, R.O.C., Genomics Research Center, Academia Sinica, Taipei 115, Taiwan, R.O.C., Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan, R.O.C.
Published online on: September 13, 2017 https://doi.org/10.3892/ijmm.2017.3133
Pages: 1520-1528

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Abstract

Antiplatelet agents have considerable benefits in the treatment of thromboembolic diseases; however, these agents still have substantial limitations due to their severe side-effects. In this study, the antiplatelet activity of three newly synthesized saccharide based benzimidazole derivatives, M3BIM, Malto-BIM and Melibio-BIM, in collagen and thrombin-stimulated human platelets in vitro was examined. Among the compounds tested, only compound M3BIM exerted concentration (20-60 µM)-dependent inhibitory effects against collagen (1 µg/ml) and thrombin (0.01 U/ml)-induced washed human platelet aggregation. Moreover, at a concentration of 60 µM, M3BIM distinctly abolished collagen-induced adenosine triphosphate (ATP) release and intracellular Ca2+ mobilization. Additionally, this compound attenuated the collagen-induced phosphorylation of p47, a marker of the activation of protein kinase C (PKC) and p38 mitogen-activated protein kinase (MAPK). However, Malto-BIM and Melibio-BIM were not effective in this regard. Moreover, the toxic effects of these compounds were evaluated using zebrafish embryo toxicity (ZET) assay, and the results revealed that all three compounds had no comparative cytotoxicity within the range of 25-200 µM. Overall, the results of this study provide evidence for the inhibitory effects of M3BIM on collagen-induced platelet aggregation in vitro compared to other imidazole derivatives. The presence of 1-imidazolyl moiety at one end with a longer chain length (three sugar moieties) may be mainly responsible for the observed effects of M3BIM. These results suggest that compound M3BIM may be used as a potential candidate for the treatment of aberrant platelet activation-related diseases as it inhibits the activation of p47 and p38 MAPK, and reduces ATP release and Ca2+ mobilization.

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1	Murray CJ and Lopez AD: Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet. 349:1269–1276. 1997. View Article : Google Scholar : PubMed/NCBI
2	Tantry US, Bliden KP and Gurbel PA: Resistance to anti-platelet drugs: Current status and future research. Expert Opin Pharmacother. 6:2027–2045. 2005. View Article : Google Scholar : PubMed/NCBI
3	Cox D: Oral GPIIb/IIIa antagonists: What went wrong? Curr Pharm Des. 10:1587–1596. 2004. View Article : Google Scholar : PubMed/NCBI
4	Herbert JM, Hérault JP, Bernat A, Savi P, Schaeffer P, Driguez PA, Duchaussoy P and Petitou M: SR123781A, a synthetic heparin mimetic. Thromb Haemost. 85:852–860. 2001.PubMed/NCBI
5	Petitou M, Hérault JP, Bernat A, Driguez PA, Duchaussoy P, Lormeau JC and Herbert JM: Synthesis of thrombin-inhibiting heparin mimetics without side effects. Nature. 398:417–422. 1999. View Article : Google Scholar : PubMed/NCBI
6	Dogné JM, Hanson J, de Leval X, Masereel B, Kolh P and Pirotte B: New developments on thromboxane modulators. Mini Rev Med Chem. 4:649–657. 2004. View Article : Google Scholar : PubMed/NCBI
7	Zhao Z, Arnaiz DO, Griedel B, Sakata S, Dallas JL, Whitlow M, Trinh L, Post J, Liang A, Morrissey MM and Shaw KJ: Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors. Bioorg Med Chem Lett. 10:963–966. 2000. View Article : Google Scholar : PubMed/NCBI
8	Kucheryavenko AF, Spasov AA, Petrov VI and Anisimova VA: Antiaggregant activity of a new benzimidazole derivative. Bull Exp Biol Med. 156:796–798. 2014. View Article : Google Scholar : PubMed/NCBI
9	Greinacher A, Alban S, Dummel V, Franz G and Mueller-Eckhardt C: Characterization of the structural requirements for a carbohydrate based anticoagulant with a reduced risk of inducing the immunological type of heparin-associated thrombocytopenia. Thromb Haemost. 74:886–892. 1995.PubMed/NCBI
10	Lin C, Lai PT, Liao SK, Hung WT, Yang WB and Fang JM: Using molecular iodine in direct oxidative condensation of aldoses with diamines: An improved synthesis of aldo-benzimidazoles and aldo-naphthimidazoles for carbohydrate analysis. J Org Chem. 73:3848–3853. 2008. View Article : Google Scholar : PubMed/NCBI
11	Sheu JR, Lee CR, Lin CH, Hsiao G, Ko WC, Chen YC and Yen MH: Mechanisms involved in the antiplatelet activity of Staphylococcus aureus lipoteichoic acid in human platelets. Thromb Haemost. 83:777–784. 2000.PubMed/NCBI
12	Westerfield M: The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Brachydanio rerio). University of Oregon Press; Eugene, OR: 1993
13	Mackman N: Triggers, targets and treatments for thrombosis. Nature. 451:914–918. 2008. View Article : Google Scholar : PubMed/NCBI
14	Kang WS, Chung KH, Chung JH, Lee JY, Park JB, Zhang YH, Yoo HS and Yun YP: Antiplatelet activity of green tea catechins is mediated by inhibition of cytoplasmic calcium increase. J Cardiovasc Pharmacol. 38:875–884. 2001. View Article : Google Scholar : PubMed/NCBI
15	Tyers M, Rachubinski RA, Stewart MI, Varrichio AM, Shorr RG, Haslam RJ and Harley CB: Molecular cloning and expression of the major protein kinase C substrate of platelets. Nature. 333:470–473. 1988. View Article : Google Scholar : PubMed/NCBI
16	Toth-Zsamboki E, Oury C, Cornelissen H, De Vos R, Vermylen J and Hoylaerts MF: P2X1-mediated ERK2 activation amplifies the collagen-induced platelet secretion by enhancing myosin light chain kinase activation. J Biol Chem. 278:46661–46667. 2003. View Article : Google Scholar : PubMed/NCBI
17	Nofal ZM, Soliman EA, Abd El-Karim SS, El Zahar MI, Srour AM, Sethumadhavan S and Maher TJ: Novel benzimidazole derivatives as expected anticancer agents. Acta Pol Pharm. 68:519–534. 2011.PubMed/NCBI
18	Unsworth AJ, Smith H, Gissen P, Watson SP and Pears CJ: Submaximal inhibition of protein kinase C restores ADP-induced dense granule secretion in platelets in the presence of Ca²⁺. J Biol Chem. 286:21073–21082. 2011. View Article : Google Scholar : PubMed/NCBI
19	Roberts DE, McNicol A and Bose R: Mechanism of collagen activation in human platelets. J Biol Chem. 279:19421–19430. 2004. View Article : Google Scholar : PubMed/NCBI
20	Roberts DE and Bose R: Reverse mode Na+/Ca²⁺ exchange in the collagen activation of human platelets. Ann NY Acad Sci. 976:345–349. 2002. View Article : Google Scholar
21	Lu WJ, Lee JJ, Chou DS, Jayakumar T, Fong TH, Hsiao G and Sheu JR: A novel role of andrographolide, an NF-kappa B inhibitor, on inhibition of platelet activation: The pivotal mechanisms of endothelial nitric oxide synthase/cyclic GMP. J Mol Med (Berl). 89:1261–1273. 2011. View Article : Google Scholar
22	Jayakumar T, Chen WF, Lu WJ, Chou DS, Hsiao G, Hsu CY, Sheu JR and Hsieh CY: A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase: Ex vivo and in vivo studies. J Nutr Biochem. 24:1086–1095. 2013. View Article : Google Scholar
23	Chang Y, Hsu WH, Lu WJ, Jayakumar T, Liao JC, Lin MJ, Wang SH, Geraldine P, Lin KH and Sheu JR: Inhibitory mechanisms of CME-1, a novel polysaccharide from the mycelia of Cordyceps sinensis, in platelet activation. Curr Pharm Biotechnol. 16:451–461. 2015. View Article : Google Scholar : PubMed/NCBI
24	Rakesh KS, Jagadish S, Vinayaka AC, Hemshekhar M, Paul M, Thushara RM, Sundaram MS, Swaroop TR, Mohan CD, Basappa, et al: A new ibuprofen derivative inhibits platelet aggregation and ROS mediated platelet apoptosis. PLoS One. 9:e1071822014. View Article : Google Scholar : PubMed/NCBI
25	Bugaud F, Nadal-Wollbold F, Lévy-Toledano S, Rosa JP and Bryckaert M: Regulation of c-jun-NH2 terminal kinase and extracellular-signal regulated kinase in human platelets. Blood. 94:3800–3805. 1999.PubMed/NCBI
26	Coulon L, Calzada C, Moulin P, Véricel E and Lagarde M: Activation of p38 mitogen-activated protein kinase/cytosolic phospholipase A2 cascade in hydroperoxide-stressed platelets. Free Radic Biol Med. 35:616–625. 2003. View Article : Google Scholar : PubMed/NCBI
27	Tyers M, Haslam RJ, Rachubinski RA and Harley CB: Molecular analysis of pleckstrin: The major protein kinase C substrate of platelets. J Cell Biochem. 40:133–145. 1989. View Article : Google Scholar : PubMed/NCBI
28	Lu WJ, Chang NC, Jayakumar T, Liao JC, Lin MJ, Wang SH, Chou DS, Thomas PA and Sheu JR: Ex vivo and in vivo studies of CME-1, a novel polysaccharide purified from the mycelia of Cordyceps sinensis that inhibits human platelet activation by activating adenylate cyclase/cyclic AMP. Thromb Res. 134:1301–1310. 2014. View Article : Google Scholar : PubMed/NCBI
29	Lin KH, Kuo JR, Lu WJ, Chung CL, Chou DS, Huang SY, Lee HC and Sheu JR: Hinokitiol inhibits platelet activation ex vivo and thrombus formation in vivo. Biochem Pharmacol. 85:1478–1485. 2013. View Article : Google Scholar : PubMed/NCBI
30	He N, Li X, Feng D, Wu M, Chen R, Chen T, Chen D and Feng X: Exploring the toxicity of a bismuth-asparagine coordination polymer on the early development of zebrafish embryos. Chem Res Toxicol. 26:89–95. 2013. View Article : Google Scholar
31	Chen MC, Zhou B, Zhang K, Yuan YC, Un F, Hu S, Chou CM, Chen CH, Wu J, Wang Y, et al: The novel ribonucleotide reductase inhibitor COH29 inhibits DNA repair in vitro. Mol Pharmacol. 87:996–1005. 2015. View Article : Google Scholar : PubMed/NCBI
32	Sittaramane V, Padgett J, Salter P, Williams A, Luke S, McCall R, Arambula JF, Graves VB, Blocker M, Van Leuven D, et al: Discovery of quinoline-derived trifluoromethyl alcohols, determination of their in vivo toxicity and anticancer activity in a zebrafish embryo model. ChemMedChem. 10:1802–1807. 2015. View Article : Google Scholar : PubMed/NCBI
33	Yang J and Chan KM: Evaluation of the toxic effects of brominated compounds (BDE-47, 99, 209, TBBPA) and bisphenol A (BPA) using a zebrafish liver cell line, ZFL. Aquat Toxicol. 159:138–147. 2015. View Article : Google Scholar
34	Sathler PC, Santana M, Lourenço AL, Rodrigues CR, Abreu P, Cabral LM and Castro HC: Human thromboxane synthase: Comparative modeling and docking evaluation with the competitive inhibitors Dazoxiben and Ozagrel. J Enzyme Inhib Med Chem. 29:527–531. 2014. View Article : Google Scholar
35	Lourenço AL, Saito MS, Dorneles LE, Viana GM, Sathler PC, Aguiar LC, de Pádula M, Domingos TF, Fraga AG, Rodrigues CR, et al: Synthesis and antiplatelet activity of antithrombotic thiourea compounds: Biological and structure-activity relationship studies. Molecules. 20:7174–7200. 2015. View Article : Google Scholar : PubMed/NCBI
36	Liedtke AJ, Crews BC, Daniel CM, Blobaum AL, Kingsley PJ, Ghebreselasie K and Marnett LJ: Cyclooxygenase-1-selective inhibitors based on the (E)-2′-des-methyl-sulindac sulfide scaffold. J Med Chem. 55:2287–2300. 2012. View Article : Google Scholar : PubMed/NCBI
37	Reyes JJ, De La Cruz JP, Muñoz-Marin J, Guerrero A, Lopez-Villodres JA, Madrona A, Espartero JL and Gonzalez-Correa JA: Antiplatelet effect of new lipophilic hydroxytyrosol alkyl ether derivatives in human blood. Eur J Nutr. 52:591–599. 2013. View Article : Google Scholar
38	Guo C, Liu S, Guo Y, Yin Y, Lin J, Chen X and Sun MZ: Comparative function-structural analysis of antiplatelet and antiradical activities of flavonoid phytochemicals. J Anim Plant Sci. 24:926–935. 2014.