Abstract
A series of novel biphenyl–furocoumarin derivatives were synthesized and evaluated for their vasorelaxant activities in vitro against rat mesenteric artery, basilar artery, and renal artery ring models pre-contracted by high KCl. The results showed that compounds 12b, 13b, 13d, 14b, and 14d exhibited good broad spectrum vasorelaxant activities on three kinds of rat artery ring models compared to imperatorin. Noteworthy, most of the compounds had potent good selectivity against mesenteric artery in which compound 14c exhibited highest vasodilation activity (pEC50 = 6.44, E max = 105.8 %). These were suggested that the introduction of biphenyl in imperatorin was useful to improve vasodilation activities. The preliminary structure–activity relationships studies revealed that larger halogen substituent R 1 on phenyl ring and smaller nitrogenous base R 2 were favorable for vasorelaxant activities. In addition, the CoMFA model showed acceptable correlative and predictive abilities (r 2 = 0.875, q 2 = 0.502).
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Adams SS (1999) Ibuprofen, the propionics and NSAIDs: personal reflections over four decades. Inflammopharmacology 7:191–197
Adebajo AC, Iwalewa EO, Obuotor EM, Ibikunle GF, Omisore NO, Adewunmi CO, Obaparusi OO, Klaes M, Adetogun GE, Schmidt TJ, Verspohl EJ (2009) Pharmacological properties of the extract and some isolated compounds of Clausena lansium stem bark: Anti-trichomonal, antidiabetic, anti-inflammatory, hepatoprotective and antioxidant effects. J Ethnopharmacol 122:10–19
Adel SG, Nasser SMI, Hanaa F (2011) Facile synthesis, vasorelaxant properties and molecular modeling studies of 2-amino-8a-methoxy-4H-pyrano[3,2-c]pyridine-3-carbonitriles. Eur J Med Chem 46:2397–2407
Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS, Wang B, Bukofzer GT, Wang YC, Stavropoulos JA, Hartandi K, Niquette AL, Soni N, Johnson EF, McCall JO, Bouska JJ, Luo Y, Donawho CK, Dai Y, Marcotte PA, Glaser KB, Michaelides MR, Davidsen SK (2006) Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol Cancer Ther 5:995–1006
Baek NI, Ahn EM, Kim HY, Park YD (2000) Furanocoumarins from the root of Angelica dahurica. Arch Pharm Res 23:467–470
Balafa O, Kalaitzidis R, Siamopoulos KC (2013) Optimal medical management in patients with renovascular hypertension. Am J Cardiovasc Drug 13:71–78
Brokke ME, Christensen BE (1958) Psoralene I: certain reactions of Xanthotoxin. J Org Chem 23:589–596
Bühlmayer P, Furet P, Criscione L, de Gasparo M, Whitebread S, Schmidlin T, Lattmann R, Wood J (1994) Valsartan, a potent, orally active angiotensin II antagonist developed from the structurally new amino acid series. Bioorg Med Chem Lett 4:29–34
Ceska O, Chaudhary SK, Warrington PJ, Ashwood-Smith MJ (1987) Photoactive furanocoumarins in fruits of some Umbellifers. Phytochemistry 26:165–169
Chang KSK, Stevens WC (1992) Endothelium-dependent increase in vascular sensitivity to phenylephrine in long-term streptozotocin diabetic rat aorta. Br J Pharmacol 107:983–990
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Toccella JR (2003) The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA 289:2560–2572
Cowart M, Faghih R, Curtis MP, Gfesser GA, Bennani YL, Black LA, Pan L, Marsh KC, Sullivan JP, Esbenshade TA, Fox GB, Hancock AA (2005) 4-(2-[2-(2(R)-Methylpyrrolidin-1-yl)ethyl]benzofuran-5-yl)benzonitrile and related 2-aminoethylbenzofuran H3 receptor antagonists potently enhance cognition and attention. J Med Chem 48:38–55
Cramer RD, Patterson DE, Bunce JD (1988) Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins. J Am Chem Soc 110:5959–5967
Crandell WB, Pappas SG, MacDonald A (1966) Nephrotoxicity associated with methoxyflurane anesthesia. Anesthesiology 27:591–607
Denis BT, Boris SZ (2009) Structural model for dihydropyridine binding to l-type calcium channels. J Biol Chem 284:19006–19017
Dong X, Liu Y, Yan J, Jiang C, Chen J, Liu T, Hu Y (2008) Identification of SVM-based classification model, synthesis and evaluation of prenylated flavonoids as vasorelaxant agents. Bioorg Med Chem 16:8151–8160
Duncia JV, Carini DJ, Chiu AT, Johnson AL, Price WA, Wong PC, Wexler RR, Timmermans PBMWM (1992) The discovery of DuP-753, a potent, orally active nonpeptide angiotensin II receptor antagonist. Med Res Rev 12:149–191
Fatemi MH, Gharaghani S (2007) A novel QSAR model for prediction of apoptosis-inducing activity of 4-aryl-4-H-chromenes based on support vector machine. Bioorg Med Chem 15:7746–7754
Gwaltney SL, O’Connor SJ, Nelson LT, Sullivan GM, Imade H, Wang W, Hasvold L, Li Q, Cohen J, Gu WZ, Tahir SK, Bauch J, Marsh K, Ng SC, Frost DJ, Zhang H, Muchmore S, Jakob CG, Stoll V, Hutchins C, Rosenberg SH, Sham HL (2003) Aryl tetrahydropyridine inhibitors of farnesyltransferase: Glycine, phenylalanine and histidine derivatives. Bioorg Med Chem Lett 13:1359–1362
Hajduk PJ, Bures M, Praestgaard J, Fesik SWJ (2000) Privileged molecules for protein binding identified from NMR-based screening. J Med Chem 43:3443–3447
Hametner C, Kellert L, Veltkamp R, Behrens L, Nagel S, Hacke W, Ringleb P (2014) Prolonged low-dose thrombolysis in posterior circulation stroke. Neurocrit Care 21:114–118
He JY, Zhang W, He LC, Cao YX (2007) Imperatorin induces vasodilatation possibly via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release. Eur J Pharmacol 573:170–175
Horton DA, Bourne GT, Smythe ML (2003) The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chem Rev 103:893–930
Hou XF, Zhou MZ, Jiang Q, Wang SC, He LC (2009) A vascular smooth muscle/cell membrane chromatography–offline-gas chromatography/mass spectrometry method for recognition, separation and identification of active components from traditional Chinese medicines. J Chromatogr A 1216:7081–7087
Husedzinović I, Bradić N, Goranović T (2006) Vasoactive agents. Signa Vitae 1:9–12
Jackman KA, Woodman OL, Sobey CG (2007) Isoflavones, equol and cardiovascular disease: pharmacological and therapeutic insights. Curr Med Chem 14:2824–2830
Jia Z, Jiang G, Tian F, Zhao J, Li S, Wang K, Wang Y, Jiang L, Wang W (2014) Early endovascular treatment of superior mesenteric occlusion secondary to thromboemboli. Eur J Vasc Endovasc Surg 47:196–203
Kaźmierczak W (2009) The usefulness of some vestibular tests in the diagnosis and treatment of patients with vertebro-basilar insufficiency. Otolaryngol Pol 63:373–374
Koenig A, Roegler C, Lange K, Daiber A, Glusa E, Lehmann J (2007) NO donors. Part 16: Investigations on structure-activity relationships of organic mononitrates reveal 2-nitrooxyethylammoniumnitrate as a high potent vasodilator. Bioorg Med Chem Lett 17:5881–5885
Li N, He JY, Zhan YZ, Zhou N, Zhang J (2011) Design, synthesis and preliminary evaluation of novel imperatorin derivatives as vasorelaxant agents. Med Chem 7:18–23
Luszczki JJ, Wojda E, Andres-Mach M, Cisowski W, Glensk M, Glowniak K, Czuczwar SJ (2009) Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: A comparative study. Epilepsy Res 85:293–299
Metrangolo P, Meyer F, Pilati T, Resnati G, Terraneo G (2008) Halogen bonding in supramolecular chemistry. Angew Chem Int Ed 47:6114–6127
Murugesan N, Gu Z, Spergel S, Young M, Chen P, Mathur A, Leith L, Hermsmeier M, Liu EC, Zhang R, Bird E, Waldron T, Marino A, Koplowitz B, Humphreys WG, Chong S, Morrison RA, Webb ML, Moreland S, Trippodo N, Barrish JC (2003) Biphenylsulfonamide endothelin receptor antagonists. 4. Discovery of N-[[2’-[[(4,5-dimethyl-3-isoxazolyl)amino]sulfonyl]-4-(2-oxazolyl)[1,1’-biphenyl]-2-yl]methyl]-N,3,3-trimethylbutanamide (BMS-207940), a highly potent and orally active ETA selective antagonist. J Med Chem 46:125–137
Nicolaou KC, Boddy CNC, Bräse S, Winssinger N (1999) Chemistry, biology, and medicine of the glycopeptide antibiotics. Angew Chem Int Ed 38:2096–2152
O’Hagan D, Schaffrath C, Cobb SL, Hamilton JT, Murphy CD (2002) Biochemistry: biosynthesis of an organofluorine molecule. Nature 416:279
Park BK, Kitteringham NR (1994) Effects of fluorine substitution on drug-metabolism pharmacological and toxicological implications. Drug Metab Rev 26:605–643
Rush JWE, Denniss SG, Graham DA (2005) Vascular nitric oxide and oxidative stress: determinants of endothelial adaptations to cardiovascular disease and physical activity. Can J Appl Physiol 30:442–474
Seewaldt-Becker E, Himmelsbach F, Mueller TH (1993) Biology of vitronectins and their receptors. Excerpta medica international congress series, vol 1042. Elsevier, Cambridge, pp 157–162
Stahlmann R (2002) Clinical toxicological aspects of fluoroquinolones. Toxicol Lett 127:269–277
Tongqian C, Shashi SK, Helena MP, Matthew SP (1999) Psoralen sensitizers for viral inactivation. US Patent US5919935 A
Voth AR, Hays FA, Ho PS (2007) Directing macromolecular conformation through halogen bonds. Proc Natl Acad Sci USA 104:6188–6193
Wakselman C (1999) Fluorinated organic compounds: synthesis and biological applications (In French). Ann Pharm Fr 57:108–115
Wang SJ, Lin TY, Lu CW, Huang WJ (2008) Osthole and imperatorin, the active constituents of Cnidium monnieri (L.) Cusson, facilitate glutamate release from rat hippocampal nerve terminals. Neurochem Int 53:416–423
Welsch M, Bloch JG, Stephan D, Bloch R, Imbs JL (1990) Iatrogenic fluorosis. 2 cases (In French). Therapie 45:419–422
Wexler RR, Greenlee WJ, Irvin JD, Goldberg MR, Prendergast K, Smith RD, Timmermans PBMWM (1996) Nonpeptide angiotensin II receptor antagonists: the next generation in antihypertensive therapy. J Med Chem 39:625–656
Widelski J, Popova M, Graikou K, Glowniak K, Chinou I (2009) Coumarins from Angelica lucida L.—antibacterial activities. Molecules 14:2729–2734
Wold S, Albano C, Dunn WJ, Edlund U, Esbensen K, Geladi P, Hellberg S, Johansson E, Lindberg W, Sjöström M (1984) Multivariate data analysis in chemistry. In: Kowalski BR (ed) Chemometrics, mathematics and statistics in chemistry. D Reidel Publ Co, Dodrecht, pp 17–95
Xu YC, Leung SWS, Yeung DKY, Hu LH, Chen GH, Che CM, Man RYK (2007) Structure–activity relationships of flavonoids for vascular relaxation in porcine coronary artery. Phytochemistry 68:1179–1188
Yang GF, Huang XQ (2006) Development of quantitative structure-activity relationships and its application in rational drug design. Curr Pharm Des 12:4601–4611
Zhou N, He JY, Wang T, Zhang J, He HZ (2013) Design, synthesis, and vasorelaxation activity of novel imperatorin derivatives. J Asian Nat Prod Res 15:650–657
Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (No. 81202494, 30730110). We are grateful to Prof. Zongru Guo for practical guidance during the course of this project.
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Wang, T., Wang, C., Zhou, N. et al. Synthesis and vasorelaxation evaluation of novel biphenyl–furocoumarin derivatives. Med Chem Res 24, 2417–2431 (2015). https://doi.org/10.1007/s00044-014-1303-7
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DOI: https://doi.org/10.1007/s00044-014-1303-7