Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis of Novel 8-Hydroxyquinoline Derivatives through Mannich Reaction and their Biological Evaluation as Potential Immunomodulatory Agents

Author(s): Shaheen Faizi*, Tahira Sarfaraz, Saima Sumbul, Almas Jabeen, Sobia A. Halim, Mohammad A. Mesaik and Zaheer Ul-Haq*

Volume 16, Issue 4, 2020

Page: [531 - 543] Pages: 13

DOI: 10.2174/1573406415666190626121650

Price: $65

Abstract

Background: In continuation of our work on Mannich reaction on 8-hydroxyquinoline, fifteen different combinations of aromatic aldehydes and aniline were subjected to Mannich reaction from which twelve products (eight Mannich bases, two imines and two intramolecularly cyclized products with benzofuranone skeleton) were obtained. Among them six compounds (1, 2, 6, 8, 9 and 12) are the new compounds. The structures of the compounds were characterized by UV, IR, MS and 1H NMR.

Methods: The compounds were tested for the inhibition of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) at a concentration of 25 µg/mL. The cytokines were produced by THP-1 cells differentiated with PMA for 24hrs and stimulated with LPS for 4 hrs and supernatant were analyzed through ELISA technique.

Results and Discussion: Compounds 1-5, 8 and 9 inhibited the production of TNF-α and IL-1β. Compounds 1, 3, and 8 exerted potent inhibitions of TNF-α with 71%, 71%, and 83% inhibition, respectively. Compounds 1 and 8 significantly inhibited the production of IL-1β with 64% and 78% inhibition, respectively.

Conclusion: Compounds 1 and 8 significantly inhibited the production of IL-1β with 64% and 78% inhibition, respectively. Notably compound 8 showed the most potent inhibition of these cytokines. Additionally, the effect of compounds on viability of THP-1 cells was also evaluated. Moreover, molecular docking was carried out to study the mechanism of inhibition of TNF-α production.

Keywords: 8-Hydroxyquinoline, aromatic aldehydes, aniline, mannich base, benzofuranone, imine, immunomodulatory, TNF- α and IL-1β, molecular docking.

« Previous Next »
Graphical Abstract

[1]
Collin, G.; Höke, H. Quinoline and isoquinoline; Wiley and Sons: New Jersey, 2000.
[http://dx.doi.org/10.1002/14356007.a22_465]
[2]
Albert, A.; Phillips, J.N. Ionization constants of heterocyclic substances. Part II. Hydroxy-derivatives of nitrogenous six-membered ring-compounds. J. Chem. Soc. (Resumed), 1956, 264, 1294-1304.
[http://dx.doi.org/10.1039/jr9560001294]
[3]
Al-Busafi, S.N.; Suliman, F.E.O.; Al-Alawi, Z.R. 8-hydroxyquino-line and its derivatives: Synthesis and applications. Res. Rev. J. Chem., 2013, 3, 1-10.
[4]
Ahmad, E.F.; Allam, G.; Abu-Elsaad, A.S.; Maghrabi, I.A.; Alghamdi, A.H. Synthesis, anti-schistosomal activity and molecular modeling of two novel 8-hydroxyquinoline derivatives. Antiinfect. Agents, 2013, 11, 31-40.
[5]
Blicke, F.F. Synthesis of 6-methoxy-8-(4′-aminopentyl) aminoquinoline., 2011.
[6]
Saranya, S.; Harry, N.A.; Krishnan, K.K.; Anilkumar, G. Recent developments and perspectives in the asymmetric mannich reaction. Asian J. Org. Chem., 2018, 7, 613-633.
[http://dx.doi.org/10.1002/ajoc.201700679]
[7]
Subramaniapillai, S.G. Mannich reaction: A versatile and convenient approach to bioactive skeletons. J. Chem. Sci., 2013, 125, 467-482.
[http://dx.doi.org/10.1007/s12039-013-0405-y]
[8]
Turner, M.D.; Nedjai, B.; Hurst, T.; Pennington, D.J. Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochim. Biophys. Acta, 2014, 1843(11), 2563-2582.
[http://dx.doi.org/10.1016/j.bbamcr.2014.05.014] [PMID: 24892271]
[9]
Feldmann, M.; Brennan, F.M.; Foxwell, B.M.J.; Maini, R.M. The role of TNFα and IL-1 in rheumatoid arthritis. In: The role of TNFα and IL-1 in rheumatoid arthritis; ; J.J.R. Goronzy, M.N.; C.M.R. Weyand, M.N, Ed.;.. Karger Publishers: Basel, 2001, Vol. 3, pp. 188-199.
[10]
Jabeen, A.; Mesaik, M.A.; Simjee, S.U. Lubna.; Bano, S.; Faizi, S. Anti-TNF-α and anti-arthritic effect of patuletin: A rare flavonoid from Tagetes patula. Int. Immunopharmacol., 2016, 36, 232-240.
[http://dx.doi.org/10.1016/j.intimp.2016.04.034] [PMID: 27177082]
[11]
Mbiantcha, M.; Almas, J.; Shabana, S.U.; Nida, D.; Aisha, F. Anti-arthritic property of crude extracts of Piptadeniastrum africanum (Mimosaceae) in complete Freund’s adjuvant-induced arthritis in rats. BMC Complement. Altern. Med., 2017, 17(1), 111-127.
[http://dx.doi.org/10.1186/s12906-017-1623-5] [PMID: 28202019]
[12]
Vervoordeldonk, M.J.B.M.; Tak, P.P. Cytokines in rheumatoid arthritis. Curr. Rheumatol. Rep., 2002, 4(3), 208-217.
[http://dx.doi.org/10.1007/s11926-002-0067-0] [PMID: 12010605]
[13]
McInnes, I.B.; Schett, G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat. Rev. Immunol., 2007, 7(6), 429-442.
[http://dx.doi.org/10.1038/nri2094] [PMID: 17525752]
[14]
Siddiqi, H.; Faizi, S.; Naz, S.; Zahir, E. Synthesis of mannich bases of 8-Hydroxyquinoline. J. Basic Appl. Sci., 2015, 11, 539-543.
[http://dx.doi.org/10.6000/1927-5129.2015.11.71]
[15]
Mastoor, S. Kamran; Saleem, R.; Faizi, S. Synthesis of 8-Quinolinol Mannich Reaction Products. RADS J. Pharm. Pharm. Sci., 2018, 6, 138-143.
[16]
Saeed, S.A.; Simjee, R.U.; Gilani, A.H.; Siddiqui, S.; Saleem, R.; Faizi, S.; Siddiqui, B.; Farnaz, S. 8-Hydroxyquinoline and its derivatives: potential inhibitors of platelet aggregation. Biochem. Soc. Trans., 1992, 20(4), 357S.
[http://dx.doi.org/10.1042/bst020357s] [PMID: 1487018]
[17]
MOEv2014.09, Chemical Computing Group ULC, 1010 Sherbooke St. West, Suite 910, Montreal, QC, Canada..
[18]
Tabei, K.; Saitou, E. The nuclear magnetic resonance and infrared spectra of aromatic azomethines. Bull. Chem. Soc. Jap.,1969, 42, 1440-1443. (b) Odian, G.; Yang, N.-I.; Wei, Y. Substituent effects on 1H NMR spectra of 4-and 4′-substituted tras-N-benzylidene-anilines in acidic solution. Mag. Res. Chem., 1985, 23, 908-915. (c) Tsuno, Y.; Fujio, M.; Takai, Y.; Yukawa, Y. The Substituent Effect. IV. Proton NMR chemical shifts of phenols. Bull. Chem. Soc. Jap., 1972, 45, 1519-1529. (d) Echevarria, A.; Miller, J.; Nascimento, M. G. 13C NMR and azomethine 1H NMR spectra of substituted N-benzylideneanilines and hammett correlations. Mag. Res. Chem., 1985, 23, 809-813. (e) Gaber, M.; Mohamed, G.B.; Adb-El-Ghafar, M. On the formation of 1:2 (Donor:Acceptor) CT Complexes between hydroxy aromatic schiff base donors and nitrobenzenes acceptors. J. Chem. Soc. Pak, 1987, 9, 423-429. (f) Zhao, F.; Liu, Z.-Q. The protective effect of hydroxyl-substituted Schiff bases on the radical-induced oxidation of DNA. J. Phys. Org. Chem., 2009, 22, 791-798.
[19]
(a)Phillips, J.P.; Barrall, E.M. Notes - Betti Reactions of Some Phenols. J. Org. Chem., 1956, 21, 692-694.
[http://dx.doi.org/10.1021/jo01112a606]
(b)Braude, M.B.; Stavrovskaya, V. Synthesis of 6-methoxy-8-(4′-aminopentyl) aminoquinoline. Zhur. Obs. Khim., 1956, 26, 878-881.
[20]
Issa, Y.M.; El Ansary, A.L.; Sherif, O.E.; Hassib, H.B. Charge–transfer complexes of pyrimidine Schiff bases with aromatic nitro compounds. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2011, 79, 513-521.
[21]
Scholz, G.; Pohl, I.; Genschow, E.; Klemm, M.; Spielmann, H. Embryotoxicity screening using embryonic stem cells in vitro: correlation to in vivo teratogenicity. Cells Tissues Organs (Print), 1999, 165(3-4), 203-211.
[http://dx.doi.org/10.1159/000016700] [PMID: 10592392]
[22]
Röbisch, G.; Schefter, W. Zur Acidität von Derivaten des 8-Hydroxychinolins. Zeits. Fuer Chem., 1975, 15, 445-446.

Rights & Permissions Print Cite
Article Metrics
14
© 2024 Bentham Science Publishers | Privacy Policy