Abstract
In this paper new β-carboline derivatives possessing the 1,2,3-triazole ring at C-1 substituent were synthesized from L-tryptophan by Pictet–Spengler reaction followed by a Huisgen 1,3-dipolar addition. In vitro cytotoxicity and antibacterial activity of synthetic compounds were investigated. Methyl 1-(3-((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-β-carboline-3-carboxylate (7f) showed the highest cytotoxic activity with IC50 values of 46 and 32 μM against Hela and HepG2 cell lines, respectively. Compounds 7d and 7i (possessing 4-bromophenyl substituent) and 5c showed excellent inhibition activity for Enterococcus faecium with MIC of 8 μg/mL. The results demonstrated that the presence of 1,2,3-triazole rings in β-carboline derivatives improve their biological activities.
Similar content being viewed by others
References
Barbosa VA, Formagio ASN, Savariz FC, Foglio MA, Spindola HM, de Carvalho JE, Meyer E, Sarragiotto MH (2011) Synthesis and antitumor activity of β-carboline 3-(substituted-carbohydrazide) derivatives. Bioorg Med Chem 19:6400–6408
Boursereau Y, Coldham I (2004) Synthesis and biological studies of 1-amino ??-carbolines. Bioorg Med Chem Lett 14:5841–5844
Braestrup C, Nielsen M, Olsen CE (1980) Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc Natl Acad Sci USA 77:2288–2292
Brahmbhatt KG, Ahmed N, Sabde S, Mitra D, Singh IP, Bhutani KK (2010) Synthesis and evaluation of beta-carboline derivatives as inhibitors of human immunodeficiency virus. Bioorg Med Chem Lett 20:4416–4419
Calderone V, Giorgi I, Livi O, Martinotti E, Mantuano E, Martelli A, Nardi A (2005) Benzoyl and/or benzyl substituted 1,2,3-triazoles as potassium channel activators. VIII. Eur J Med Chem 40:521–528
Cao R, Chen Q, Hou X, Chen H, Guan H, Ma Y, Peng W, Xu A (2004) Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives. Bioorg Med Chem 12:4613–4623
Cao R, Chen H, Peng W, Ma Y, Hou X, Guan H, Liu X, Xu A (2005) Design, synthesis and in vitro and in vivo antitumor activities of novel beta-carboline derivatives. Eur J Med Chem 40:991–1001
Cao R, Guan X, Shi B, Chen Z, Ren Z, Peng W, Song H (2010) Design, synthesis and 3D-QSAR of b -carboline derivatives as potent antitumor agents. Eur J Med Chem 45:2503–2515
Cao R, Peng W, Wang Z, Xu A (2007) β-Carboline alkaloids: biochemical and pharmacological functions. Curr Med Chem 14:479–500
Carvalho I, Andrade P, Campo VL, Guedes PMM, Sesti-Costa R, Silva JS, Schenkman S, Dedola S, Hill L, Rejzek M, Nepogodiev SA, Field RA (2010) “Click chemistry” synthesis of a library of 1,2,3-triazole-substituted galactose derivatives and their evaluation against Trypanosoma cruzi and its cell surface trans-sialidase. Bioorg Med Chem 18:2412–2427
Chauhan SS, Singh AK, Meena S, Lohani M, Singh A, Arya RK, Cheruvu SH, Sarkar J, Gayen JR, Datta D, Chauhan PMS (2014) Synthesis of novel β-carboline based chalcones with high cytotoxic activity against breast cancer cells. Bioorg Med Chem Lett 24:2820–2824
Cuny GD, Ulyanova NP, Patnaik D, Liu JF, Lin X, Auerbach K, Ray SS, Xian J, Glicksman Ma, Stein RL, Higgins JMG (2012) Structure–activity relationship study of β-carboline derivatives as haspin kinase inhibitors. Bioorg Med Chem Lett 22:2015–2019
Dabiri M, Salehi P, Bahramnejad M, Sherafat F (2010) Synthesis of diheterocyclic compounds based on triazolyl methoxy phenylquinazolines via a one-pot four-component-click reaction. J Comb Chem 12:638–42
Daoud A, Song J, Xiao F, Shang J (2014) B-9-3, a novel β-carboline derivative exhibits anti-cancer activity via induction of apoptosis and inhibition of cell migration in vitro. Eur J Pharmacol 724:219–30
Díaz L, Bujons J, Casas J, Llebaria A, Delgado A (2010) Click chemistry approach to new N-substituted aminocyclitols as potential pharmacological chaperones for Gaucher disease. J Med Chem 53:5248–55
Dighe SU, Khan S, Soni I, Jain P, Shukla S, Yadav R, Sen P, Meeran SM, Batra S (2015) Synthesis of β-carboline-based\nN\n-heterocyclic carbenes and their antiproliferative and antimetastatic activities against human breast cancer cells. J Med Chem 58:3485–3499
Duan Y-C, Ma Y-C, Zhang E, Shi X-J, Wang M-M, Ye X-W, Liu H-M (2013) Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents. Eur J Med Chem 62:11–19
de Luiza BO, Borgati TF, de Freitas RP, Ruiz ALTG, Marchetti GM, de Carvalho JE, da Cunha EFF, Ramalho TC, Alves RB (2014) Synthesis and antiproliferative activity of 8-hydroxyquinoline derivatives containing a 1,2,3-triazole moiety. Eur J Med Chem 84:595–604
Gohil VM, Brahmbhatt KG, Loiseau PM, Bhutani KK (2012) Bioorganic & medicinal chemistry letters synthesis and anti-leishmanial activity of 1-aryl-b-carboline derivatives against Leishmania donovani. Bioorg Med Chem Lett 22:3905–3907
Guan H, Chen H, Peng W, Ma Y, Cao R, Liu X, Xu A (2006) Design of β-carboline derivatives as DNA-targeting antitumor agents. Eur J Med Chem 41:1167–1179
Guantai EM, Ncokazi K, Egan TJ, Gut J, Rosenthal PJ, Smith PJ, Chibale K (2010) Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds. Bioorg Med Chem 18:8243–8256
Heravi M, Tamimi M, Yahyavi H, Hosseinnejad T (2016) Huisgen’s cycloaddition reactions: a full perspective. Curr Org Chem 20:1591–1647
Ikeda R, Kimura T, Tsutsumi T, Tamura S, Sakai N, Konakahara T (2012) Structure–activity relationship in the antitumor activity of 6-, 8- or 6,8-substituted 3-benzylamino-??-carboline derivatives. Bioorg Med Chem Lett 22:3506–3515
Ingham JD, Petty WL, Nichols Jr. PL (1956) Notes-the additon of azide ion to epoxides. J Org Chem 21:373–375
Jiménez J, Riverón-Negrete L, Abdullaev F, Espinosa-Aguirre J, Rodríguez-Arnaiz R (2008) Cytotoxicity of the β-carboline alkaloids harmine and harmaline in human cell assays in vitro. Exp Toxicol Pathol 60:381–389
Kamal A, Prabhakar S, Janaki Ramaiah M, Venkat Reddy P, Ratna Reddy C, Mallareddy A, Shankaraiah N, Lakshmi Narayan Reddy T, Pushpavalli SNCVL, Pal-Bhadra M (2011) Synthesis and anticancer activity of chalcone-pyrrolobenzodiazepine conjugates linked via 1,2,3-triazole ring side-armed with alkane spacers. Eur J Med Chem 46:3820–3831
Kamal A, Shankaraiah N, Devaiah V, Laxma Reddy K, Juvekar A, Sen S, Kurian N, Zingde S (2008) Synthesis of 1,2,3-triazole-linked pyrrolobenzodiazepine conjugates employing “click” chemistry: DNA-binding affinity and anticancer activity. Bioorg Med Chem Lett 18:1468–1473
Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl 40:2004–2021
Li Q, Tan W, Zhang C, Gu G, Guo Z (2016) Synthesis of water soluble chitosan derivatives with halogeno-1,2,3-triazole and their antifungal activity. Int J Biol Macromol. doi:10.1016/j.ijbiomac.2016.06.006
Luo Z-G, Zhao Y, Xu F, Ma C, Xu X-M, Zhang X-M (2014) Synthesis and thermal properties of novel calix[4]arene derivatives containing 1,2,3-triazole moiety via K2CO3-catalyzed 1,3-dipolar cycloaddition reaction. Chinese Chem Lett 25:1346–1348
Meldrum BS, Evans MC, Braestrup C (1983) Anticonvulsant action in the photosensitive baboon, Papio papio, of a novel β-carboline derivative, ZK 91296. Eur J Pharmacol 91:255–259
Mohebbi M, Salehi P, Bararjanian M, Aliahmadi A, Safavi-Sohi R, Ghasemi JB (2014) Synthesis, antibacterial activity, and CoMFA study of new 1,2,3-triazolyl 7-carboxamidodesacetoxy cephalosporanic acid derivatives. Med Chem Res 23:4531–4541
Naresh Kumar R, Jitender Dev G, Ravikumar N, Krishna Swaroop D, Debanjan B, Bharath G, Narsaiah B, Nishant Jain S, Gangagni Rao A (2016) Synthesis of novel triazole/isoxazole functionalized 7-(trifluoromethyl)pyrido[2,3-d]pyrimidine derivatives as promising anticancer and antibacterial agents. Bioorg Med Chem Lett 26:2927–2930
Narsimha S, Satheesh Kumar N, Kumara Swamy B, Vasudeva Reddy N, Althaf Hussain SK, Srinivasa Rao M (2016) Indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3-triazoles: synthesis, characterization and evaluation of anticancer, antibacterial, and DNA-cleavage activities. Bioorg Med Chem Lett 26:1639–1644
Nazari Formagio AS, Santos PR, Zanoli K, Ueda-Nakamura T, Düsman Tonin LT, Nakamura CV, Sarragiotto MH (2009) Synthesis and antiviral activity of β-carboline derivatives bearing a substituted carbohydrazide at C-3 against poliovirus and herpes simplex virus (HSV-1). Eur J Med Chem 44:4695–4701
Nutt DJJ, Lister RGG (1989) 3-(Methoxycarbonyl)-amino-beta-carboline reduces both the sedative and anticonvulsant effects of diazepam. Eur J Pharmacol 165:135–138
Pokhodylo NT, Matiychuk VS, Obuushak MD (2009) (Arylsulfonyl)acetones and -acetonitriles: new activated methylenic building blocks for synthesis of 1,2,3-triazoles. Synthesis (Stuttg) 2009:2321–2323
Salehi P, Dabiri M, Koohshari M, Movahed SK, Bararjanian M (2011) One-pot synthesis of 1,2,3-triazole linked dihydropyrimidinones via Huisgen 1,3-dipolar/biginelli cycloaddition. Mol Divers 15:833–837
Salehi P, MaGee DI, Dabiri M, Torkian L, Donahue J (2012) Combining click-multicomponent reaction: one-pot synthesis of triazolyl methoxy-phenyl indazolo[2,1-b]phthalazine-trione derivatives. Mol Divers 16:231–240
Shankaraiah N, Jadala C, Nekkanti S, Ram K, Nagesh N, Shrivastava S, Naidu VGM, Sathish M, Kamal A (2016) Bioorganic chemistry design and synthesis of C3-tethered 1, 2, 3-triazolo- b -carboline derivatives : anticancer activity, DNA-binding ability, viscosity and molecular modeling studies. Bioorg Chem 64:42–50
Shen L, Park E-JJ, Kondratyuk TP, Guendisch D, Marler L, Pezzuto JM, Wright AD, Sun D (2011) Design, synthesis, and biological evaluation of callophycin A and analogues as potential chemopreventive and anticancer agents. Bioorg Med Chem 19:6182–6195
Snyder HR, Hansch CH, Katz L, Parmerter SM, Spaeth EC (1948) The synthesis of derivatives of β-carboline. II. Syntheses from dl-tryptophan and aldehydes 1. J Am Chem Soc 70:219–221
Verdian Rizi MR, Hadjiakhoondi A (2007) Cytotoxicity and antimicrobial activity of harman alkaloids. J Pharmacol Toxicol 2:677–680
Reddy TVK, Jyotsna A, Prabhavathi Devi BLA, Prasad RBN, Poornachandra Y, Ganesh Kumar C (2016) Design, synthesis and in vitro biological evaluation of short-chain C12-sphinganine and its 1,2,3-triazole analogs as potential antimicrobial and anti-biofilm agents. Eur J Med Chem 118:98–106
Wu J-C, Wang D-X, Huang Z-T, Wang M-X (2010) Synthesis of diverse N,O-bridged calix[1]arene[4]pyridine-C(60) dyads and triads and formation of intramolecular self-inclusion complexes. J Org Chem 75:8604–8614
Xiao S, Lin W, Wang C, Yang M (2001) Synthesis and biological evaluation of DNA targeting flexible side-chain substituted beta-carboline derivatives. Bioorg Med Chem Lett 11:437–441
Zhao M, Bi L, Bi W, Wang C, Yang Z, Ju J, Peng S (2006a) Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity. Bioorg Med Chem 14:4761–4774
Zhao M, Bi L, Wang W, Wang C, Baudy-Floc’h M, Ju J, Peng S (2006b) Synthesis and cytotoxic activities of beta-carboline amino acid ester conjugates. Bioorg Med Chem 14:6998–7010
Zhao L, Mao L, Hong G, Yang X, Liu T (2015) Design, synthesis and anticancer activity of matrine-1H-1,2,3-triazole-chalcone conjugates. Bioorg Med Chem Lett 25:2540–2544
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare that they have no conflicts of interest.
Supplementary Data
Rights and permissions
About this article
Cite this article
Salehi, P., Babanezhad-Harikandei, K., Bararjanian, M. et al. Synthesis of novel 1,2,3-triazole tethered 1,3-disubstituted β-carboline derivatives and their cytotoxic and antibacterial activities. Med Chem Res 25, 1895–1907 (2016). https://doi.org/10.1007/s00044-016-1622-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-016-1622-y