New hybrid molecules combining benzothiophene or benzofuran with rhodanine as dual COX-1/2 and 5-LOX inhibitors: Synthesis, biological evaluation and docking study

Bioorganic Chemistry

Volumn 72, Issue , 2017, Pages 102-115

  El Miligy, Mostafa M M ^a   Hazzaa, Aly A ^a   El Messmary, Hanan ^b   Nassra, Rasha A ^c   El Hawash, Soad A M ^a  

^a Alexandria University Faculty of Pharmacy   (Egypt)

^b OMAR AL MUKHTAR UNIVERSITY   (Libyan Arab Jamahiriya)

^c ALEXANDRIA UNIVERSITY   (Egypt)

Author keywords

Benzofuran; Benzothiophene; COX LOX inhibition; Rhodanine

Indexed keywords

3 CHLORO N [4 OXO 5 (2 OXOINDOLIN 3 YLIDENE) 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; 3 CHLORO N [5 (3,4 DIMETHOXYBENZYLIDENE) 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; 3 CHLORO N [5 (4 CHLOROBENZYLIDENE) 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; 3 CHLORO N [5 (4 HYDROXY 3 METHOXYBENZYLIDENE) 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; 3 CHLORO N [5 [(1,3 DIPHENYL 1H PYRAZOL 4 YL)METHYLENE] 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; 3 CHLORO N [5 [[3 (4 METHOXYPHENYL) 1 PHENYL 1H PYRAZOL 4 YL]METHYLENE] 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; 3 CHLORON [5 (4 METHOXYBENZYLIDENE) 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; ARACHIDONATE 5 LIPOXYGENASE; BENZOFURAN DERIVATIVE; BENZOTHIOPHENE DERIVATIVE; CELECOXIB; CYCLOOXYGENASE 1; CYCLOOXYGENASE 1 INHIBITOR; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; LIPOXYGENASE INHIBITOR; MECLOFENAMATE SODIUM; N (4 OXO 2 THIOXOTHIAZOLIDIN 3 YL)BENZOFURAN 2 CARBOXAMIDE; N (5 BENZYLIDENE 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL) 3 CHLOROBENZO[B]THIOPHENE 2 CARBOXAMIDE; N [5 [(1,3 DIPHENYL 1H PYRAZOL 4 YL)METHYLENE] 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL}BENZOFURAN 2 CARBOXAMIDE; N [5 [[3 (4 BROMOPHENYL) 1 PHENYL 1H PYRAZOL 4 YL]METHYLENE] 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL)BENZOFURAN 2 CARBOXAMIDE; N [5 [[3 (4 BROMOPHENYL) 1 PHENYL 1H PYRAZOL 4 YL]METHYLENE] 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL]BENZO[B]THIOPHENE 2 CARBOXAMIDE; N [5 [[3 (4 METHOXYPHENYL) 1 PHENYL 1H PYRAZOL 4 YL]METHYLENE] 4 OXO 2 THIOXOTHIAZOLIDIN 3 YL)BENZOFURAN 2 CARBOXAMIDE; RHODANINE; UNCLASSIFIED DRUG; BENZOFURAN; BENZOTHIOPHENE; FORMALDEHYDE; NONSTEROID ANTIINFLAMMATORY AGENT; PROSTAGLANDIN SYNTHASE INHIBITOR; THIOPHENE DERIVATIVE;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BLOOD BRAIN BARRIER; CACO-2 CELL LINE; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG SYNTHESIS; ENZYME INHIBITION; HYDROGEN BOND; IC50; IN VITRO STUDY; IN VIVO STUDY; LIPOPHILICITY; MALE; MOLECULAR DOCKING; MOLECULAR MODEL; NONHUMAN; PAW EDEMA; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; RAT; SELECTIVITY INDEX; STOMACH ULCER; ULCEROGENESIS; ANIMAL; CHEMICAL STRUCTURE; CHEMICALLY INDUCED; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; EDEMA; ENZYME ACTIVE SITE; METABOLISM; STRUCTURE ACTIVITY RELATION; SYNTHESIS; WISTAR RAT;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ARACHIDONATE 5-LIPOXYGENASE; BENZOFURANS; CATALYTIC DOMAIN; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; EDEMA; FORMALDEHYDE; LIPOXYGENASE INHIBITORS; MALE; MOLECULAR DOCKING SIMULATION; MOLECULAR STRUCTURE; RATS; RATS, WISTAR; RHODANINE; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 85017119247     PISSN: 00452068     EISSN: 10902120     Source Type: Journal    
DOI: 10.1016/j.bioorg.2017.03.012     Document Type: Article

References (51)

1. [1] Yoshimura, H., Sekine, S., Adachi, H., Uematsu, Y., Mitani, A., Futaki, N., Shimizu, N., High levels of human recombinant cyclooxygenase-1 expression in mammalian cells using a novel gene amplification method. Protein Expr. Purif. 80 (2011), 41–46.
2. [2] Yao, B., Xu, J., Harris, R.C., Zhang, M.-Z., Renal localization and regulation of 15-hydroxyprostaglandin dehydrogenase. Am. J. Physiol. Renal Physiol. 294 (2008), 433–439.
3. [3] Haruna, T.S.H., Ohtsuka, Y., Yarita, Y., Fujii, T., Kudo, T., Yamashiro, Y., Pediatr. Int. 50 (2008), 1–6.
4. [4] Yoshida, S., Ujiki, M., Ding, X.Z., Pelman, C., Talamonti, M.S., Bell, R.H., Denham, W., Adrian, T.E., Pancreatic Stellate Cells (PSCs) express Cyclooxygenase-2 (COX-2) and pancreatic cancer stimulates COX-2 in PSCs. Mol. Cancer., 4, 2005, 27.
5. [5] Abdelall, E.K.A., Kamel, G.M., Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: determination of regio-specific different pyrazole cyclization by 2D NMR. Eur. J. Med. Chem. 118 (2016), 250–258.
6. [6] Garcia-Rodriguez, L.A., Hernández-Diaz, S., Nonsteroidal antiinflammatory drugs as a trigger of clinical heart failure. Epidemiology 14 (2003), 240–246.
7. [7] Ruan, C.H., So, S.P., Ruan, K.H., Inducible COX-2 dominates over COX-1 in prostacyclin biosynthesis: mechanisms of COX-2 inhibitor risk to heart disease. Life Sci. 88 (2011), 24–30.
8. [8] Khan, M., Fraser, A., Cox-2 inhibitors and the risk of cardiovascular thrombotic events. Ir. Med. J. 105 (2012), 119–121.
9. [9] Singh, P., Prasher, P., Dhillon, P., Bhatti, R., Indole based peptidomimetics as anti-inflammatory and anti-hyperalgesic agents: dual inhibition of 5-LOX and COX-2 enzymes. Eur. J. Med. Chem. 97 (2015), 104–123.
10. [10] Tries, S., Neupert, W., Laufer, S., The mechanism of action of the new antiinflammatory compound ML3000: inhibition of 5-LOX and COX-1/2. Inflamm. Res. 51 (2002), 135–143.
11. [11] Charlier, C., Michaux, C., Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur. J. Med. Chem. 38 (2003), 645–659.
12. [12] Young, R.N., Inhibitors of 5-lipoxygenase: a therapeutic potential yet to be fully realized?. Eur. J. Med. Chem. 34 (1999), 671–685.
13. [13] Lamie, P.F., Ali, W.A.M., Bazgier, V., Rárová, L., Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: synthesis, biological activities in vitro and docking study. Eur. J. Med. Chem. 123 (2016), 803–813.
14. [14] Alvaro-Gracia, J.M., Licofelone—clinical update on a novel LOX/COX inhibitor for the treatment of osteoarthritis. Rheumatology (Oxford) 43 (2004), i21–i25.
15. [15] Lu, P., Schrag, M.L., Slaughter, D.E., Raab, C.E., Shou, M., Rodrigues, A.D., Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab. Dispos. 31 (2003), 1352–1360.
16. [16] Hansen, F.K., Khankischpur, M., Tolaymat, I., Mesaros, R., Dannhardt, G., Geffken, D., Efficient synthesis and 5-LOX/COX-inhibitory activity of some 3-hydroxybenzo[b]thiophene-2-carboxylic acid derivatives. Bioorg. Med. Chem. Lett. 22 (2012), 5031–5034.
17. [17] I. Amira Pharmaceuticals, USA, L. Panmira Pharmaceuticals, Preparation of triazole derivatives as inhibitors of 5-lipoxygenase, WO2011109679A2, DOI (2011).
18. [18] Ottana, R., Maccari, R., Barreca, M.L., Bruno, G., Rotondo, A., Rossi, A., Chiricosta, G., Di Paola, R., Sautebin, L., Cuzzocrea, S., 5-Arylidene-2-imino-4-thiazolidinones: design and synthesis of novel anti-inflammatory agents. Bioorg. Med. Chem. 13 (2005), 4243–4252.
19. [19] Sunder, K.S., Maleraju, J., Synthesis of novel N-(3-chloro-4-flurophenyl)-2-(5-((3-(4-hydroxy-2, 2-dimethyl-2, 3-dihydrobenzofuran-5-yl)-1-phenyl-1H-pyrazol-4-yl) methylene)-4-oxo-2-thioxothiazolidin-3-yl) acetamides having anti-inflammatory activity. Drug Invent. Today 5 (2013), 288–295.
20. [20] Unangst, P.C., Connor, D.T., Cetenko, W.A., Sorenson, R.J., Kostlan, C.R., Sircar, J.C., Wright, C.D., Schrier, D.J., Dyer, R.D., Synthesis and biological evaluation of 5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene]oxazoles, -thiazoles, and -imidazoles: novel dual 5-lipoxygenase and cyclooxygenase inhibitors with antiinflammatory activity. J. Med. Chem. 37 (1994), 322–328.
21. [21] Kulkarni, S., Das, S., Funk, C.D., Murray, D., Cho, W., Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase. J. Biol. Chem. 277 (2002), 13167–13174.
22. [22] J.-Y.M. Fu, J.L. Seibert, K. Raz, A. Needleman, P. J., 265, Biol. Chem. 265 (1990) 16737.
23. [23] Boschelli, D.H., Connor, D.T., Hoefle, M., Bornemeier, D.A., Dyer, R.D., Conversion of NSAIDS into balanced dual inhibitors of cyclooxygenase and 5-lipoxygenase. Bioorg. Med. Chem. Lett. 2 (1992), 69–72.
24. [24] Lai, Y., Ma, L., Huang, W., Yu, X., Zhang, Y., Ji, H., Tian, J., Synthesis and biological evaluation of 3-[4-(amino/methylsulfonyl) phenyl] methylene-indolin-2-one derivatives as novel COX-1/2 and 5-LOX inhibitors. Bioorg. Med. Chem. Lett. 20 (2010), 7349–7353.
25. [25] Maier, T.J., Tausch, L., Hoernig, M., Coste, O., Schmidt, R., Angioni, C., Metzner, J., Groesch, S., Pergola, C., Steinhilber, D., Werz, O., Geisslinger, G., Celecoxib inhibits 5-lipoxygenase. Biochem. Pharmacol. 76 (2008), 862–872.
26. [26] El‐Din, M., Mahmoud, M., Senbel, A.M., Bistawroos, A.A., El‐Mallah, A., Nour El‐Din, N.A., Bekhit, A.A., Abd El Razik, H.A., A novel COX‐2 inhibitor pyrazole derivative proven effective as an anti‐inflammatory and analgesic drug. Basic Clin. Pharmacol. Toxicol. 108 (2011), 263–273.
27. [27] Argentieri, D.C., Ritchie, D.M., Ferro, M.P., Kirchner, T., Wachter, M.P., Anderson, D.W., Rosenthale, M.E., Capetola, R.J., Tepoxalin: a dual cyclooxygenase/5-lipoxygenase inhibitor of arachidonic acid metabolism with potent anti-inflammatory activity and a favorable gastrointestinal profile. J. Pharmacol. Exp. Ther. 271 (1994), 1399–1408.
28. [28] Higa, T., Krubsack, A., J, Oxidations by thionyl chloride. 8. A convenient synthesis of benzo[b]thiophenes from carboxylic acids and ketones. J. Org. Chem. 41 (1976), 3399–3403.
29. [29] Brabander, W.B.W.J.a.J., The preparation of 3-chlorobenzo[b]thiophene Derivatives from cinnamie acids. J. Heterocycl. Chem. 8 (1971), 711–714.
30. [30] Naganagowda, G., Padmashali, B., Synthesis, antimicrobial, and anthelmintic activities of some new 3-chlorobenzothiophene-2-carbonylchloride derivatives. Phosphorus, Sulfur Silicon Relat. Elem. 185 (2010), 1691–1700.
31. [31] Aboulwafa, O.M., Berto, F.A., Benzo[b]thiophenes, Part I: synthesis and antimicrobial activity of benzo[b]thienyl‐1,3,4‐oxadiazole,‐1, 2, 4‐triazoline, and‐thiazoline Derivatives. Arch. Pharm. 325 (1992), 123–127.
32. [32] Kowalewska, M., Kwiecień, H., Śmist, M., Wrześniewska, A., Synthesis of new benzofuran-2-carboxylic acid derivatives. J. Chem., 2012 2013.
33. [33] Bhardwaj, B., Jain, S.C., Synthesis of novel N′-(2-oxoindolin-3-ylidene) benzofuran-2-carbohydrazides via greener approach and their biological activities. Der Pharma Chem. 6 (2014), 272–278.
34. [34] Parekh, S., Bhavsar, D., Savant, M., Thakrar, S., Bavishi, A., Parmar, M., Vala, H., Radadiya, A., Pandya, N., Serly, J., Synthesis of some novel benzofuran-2-yl (4, 5-dihyro-3, 5-substituted diphenylpyrazol-1-yl) methanones and studies on the antiproliferative effects and reversal of multidrug resistance of human MDR1-gene transfected mouse lymphoma cells in vitro. Eur. J. Med. Chem. 46 (2011), 1942–1948.
35. [35] Halkides, C.J., Frey, P.A., Tobin, J.B., Rapid hydrogen exchange at the acetyl (C2) methyl group of acetylthiamine pyrophosphate. J. Am. Chem. Soc. 115 (1993), 3332–3333.
36. [36] Cavalla, D., Web Alert: Using the Internet for Medicinal Chemistry. Wermuth, C.G., (eds.) The Practice of Medicinal Chemistry, 2008, Academic Press, New York, 255–272.
37. [37] http://www.molinspiration.com/cgi-bin/properties.
38. [38] http://molsoft.com/mprop.
39. [39] http://preadmet.bmdrc.org.
40. [40] http://www.rdchemicals.com/drug-relevant-properties.html.
41. [41] Refsgaard, H.H.F., Jensen, B.F., Brockhoff, P.B., Guldbrandt, M., Christensen, M.S., In silico prediction of membrane permeability from calculated molecular parameters. J. Med. Chem. 48 (2005), 805–811.
42. [42] Molecular operating environment (MOE) 2008.10, Chemical Computing Group Inc., 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7. ( http://www.chemcomp.com/).
43. [43] http://www.rcsb.org/pdb/home/home.do.
44. [44] Isloor, A.M., Kalluraya, B., Pai, K.S., Synthesis, characterization and biological activities of some new benzo[b]thiophene derivatives. Eur. J. Med. Chem. 45 (2010), 825–830.
45. [45] Roschek Jr, B., Fink, R.C., Li, D., McMichael, M., Tower, C.M., Smith, R.D., Alberte, R.S., Pro-inflammatory enzymes, cyclooxygenase 1, cyclooxygenase 2, and 5-lipooxygenase, inhibited by stabilized rice bran extracts. J. Med. Food. 12 (2009), 615–623.
46. [46] Plačková, P., Šála, M., Šmídková, M., Dejmek, M., Hřebabecký, H., Nencka, R., Thibaut, H.-J., Neyts, J., Mertlíková-Kaiserová, H., 9-Norbornyl-6-chloropurine (NCP) induces cell death through GSH depletion-associated ER stress and mitochondrial dysfunction. Free Radic. Biol. Med. 97 (2016), 223–235.
47. [47] Razmi, A., Zarghi, A., Arfaee, S., Naderi, N., Faizi, M., Evaluation of anti-nociceptive and anti-inflammatory activities of novel chalcone derivatives. IJPR, 12, 2013, 153.
48. [48] Maran, S., Subramanium, P., Evaluation of anti-inflammatory and analgesic activities of methanolic leaf extract of the endangered tree species, Hildegardia populifolia (Roxb.) Schott and Endl. Int. J. Green Pharm., 9, 2015, 125.
49. [49] Rathish, I.G., Javed, K., Ahmad, S., Bano, S., Alam, M.S., Pillai, K.K., Singh, S., Bagchi, V., Synthesis and antiinflammatory activity of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide. Bioorg. Med. Chem. Lett. 19 (2009), 255–258.
50. [50] Srivastava, S., Nath, C., Gupta, M., Vrat, S., Sinha, J., Dhawan, K., Gupta, G., Protection against gastric ulcer by verapamil. Pharmacol. Res. 23 (1991), 81–86.
51. [51] Hassan, G.S., Abou-Seri, S.M., Kamel, G., Ali, M.M., Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: design, synthesis and evaluation as potential anti-inflammatory agents. Eur. J. Med. Chem. 76 (2014), 482–493.