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Synthesis and biological activity studies of new hybrid molecules containing tryptamine moiety

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Abstract

The synthesis of N′-(4-substitutedphenylsulfonyl)-2-{4-[2-(1H-indol-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetohydrazides (3a–c), 2-{4-[2-(1H-indol-3-yl)ethyl]-3-(4-chlorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl}-N′-aryl methylidene acetohydrazides (4a–f) and 4-[2-(1H-indol-3-yl)ethyl]-5-(4-substitutedbenzyl)-2-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-ones (5a, b) was performed starting from the corresponding acid hydrazides (2a, b) which was reported earlier. The treatment of 1,3,4-oxadiazole derivatives (5a, b) with hydrazine hydrate produced 4-amino-5-sulfanyl-4H-1,2,4-triazol-3-yl derivatives (6a, b). Then, compound 6b was converted to the corresponding Schiff base (7) by the treatment with anisaldehyde. The synthesis of 5-(4-chlorobenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (8) and 5-(4-methylbenzyl)-4-[2-(1H-indol-3-yl)ethyl]-2-[(4-benzyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (10) was carried out by the reaction of acid hydrazides (2a, b) with aryl iso(thio)cyanates either via the formation of the intermediates (9a, b) (for 10) or direct cyclization (for 8). 1,3-Oxa(thia)zol-2(3H)-ylidene]acetohydrazide derivatives (11a, b) were obtained by the reaction of 9a, b with 4-chlorophenacyl bromide. All newly synthesized compounds were screened for their antimicrobial activities and some of which was found to be active against the test microorganisms.

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References

  • Ahmad I, Mehmood Z, Mohammed F (1998) Screening of some Indian medicinal plants for their antimicrobial properties. J Ethnopharmacol 62:183–193

    Article  PubMed  CAS  Google Scholar 

  • Ashok M, Holla BS, Poojary B (2007) Convenient one pot synthesis and antimicrobial evaluation of some new Mannich bases carrying 4-methylthiobenzyl moiety. Eur J Med Chem 42:1095–1101

    Article  PubMed  CAS  Google Scholar 

  • Bayrak H, Demirbas A, Demirbas N, Alpay-Karaoglu S (2009a) Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities. Eur J Med Chem 44:1057–1066

    Article  PubMed  CAS  Google Scholar 

  • Bayrak H, Demirbas A, Demirbas N, Alpay-Karaoglu S (2009b) Synthesis of some new 1,2,4-triazoles starting from isonicotinic acid hydrazide and evaluation of their antimicrobial activities. Eur J Med Chem 44:4362–4366

    Article  PubMed  CAS  Google Scholar 

  • Bektas H, Karaali N, Sahin D, Demirbaş A, Alpay-Karaoglu S, Demirbas N (2010a) Synthesis of some new 1,2,4-triazoles starting from isonicotinic acid hydrazide and evaluation of their antimicrobial activities. Molecules 15:2427–2438

    Article  PubMed  CAS  Google Scholar 

  • Bektas H, Demirbas N, Demirbas A, Alpay-Karaoglu S (2010b) Synthesis of some new biheterocyclic triazole derivatives and evaluation of their antimicrobial activity. Turk J Chem 34:165–180

    CAS  Google Scholar 

  • Bonde CG, Gaikwad NJ (2004) Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones as antimicrobial agents. Bioorg Med Chem 12:2151–2161

    Article  PubMed  CAS  Google Scholar 

  • Cai S, Li QS, Borchardt RT, Kuczera K, Schowen RL (2007) The antiviral drug ribavirin is a selective inhibitor of S-adenosyl-l-homocysteine hydrolase from Trypanosoma cruzi. Bioorg Med Chem 15:7281–7287

    Article  PubMed  CAS  Google Scholar 

  • Cui Y, Dang Y, Yang Y, Zhang S, Ji R (2005) Syntheses and antibacterial activity of a series of 3-(pyridine-3-yl)-2-oxazolidinone. Eur J Med Chem 40:209–214

    Article  PubMed  CAS  Google Scholar 

  • Das B, Rudra S, Yadav A, Raj A, Rao AVSR, Srinivas ASSV, Soni A, Saini S, Shukla S, Pandya M, Bhateja P, Malhotra S, Mathur T, Arora SK, Rattan A, Mehta A (2005) Synthesis and SAR of novel oxazolidinones: discovery of ranbezolid. Bioorg Med Chem Lett 15:4261–4267

    Article  PubMed  CAS  Google Scholar 

  • Demirbas A, Johansson CB, Duman N, Ikizler AA (1996) Synthesis and biological activities of some 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Acta Pol Pharm 53:117–123

    PubMed  CAS  Google Scholar 

  • Demirbas N, Ugurluoglu R, Demirbas A (2002) Synthesis of 3-alkyl(aryl)-4-alkylidenamino-4,5-dihydro-1H–1,2,4-triazol-5-ones and 3-alkyl-4-alkylamino-4,5-dihydro-1H–1,2,4-triazol-5-ones as antitumor agents. Bioorg Med Chem 10:3717–3723

    Article  PubMed  CAS  Google Scholar 

  • Demirbas N, Demirbas A, Alpay-Karaoglu S, Çelik E (2005) Synthesis and antimicrobial activities of some new [1,2,4] triazolo[3,4-b][1,3,4]thiadiazoles and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines. Arkivoc i:75–91

    Google Scholar 

  • Demirbas A, Ceylan S, Demirbas N (2007) Synthesis of some new five membered heterocycles, a facile synthesis of oxazolidinones. J Heterocycl Chem 44:1271–1280

    Article  CAS  Google Scholar 

  • Demirbas A, Sahin D, Demirbas N, Alpay-Karaoglu S (2009) Synthesis of some new 1,3,4-thiadiazol-2-ylmethyl-1,2,4-triazole derivatives and investigation of their antimicrobial activities. Eur J Med Chem 44:2896–2903

    Article  PubMed  CAS  Google Scholar 

  • Dixit PP, Patil VJ, Nair PS, Jain S, Sinha N, Arora SK (2006) Synthesis of 1-[3-(4-benzotriazol-1/2-yl-3-fluoro-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-3-substituted-thiourea derivatives as antituberculosis agents. Eur J Med Chem 41:423–428

    Article  PubMed  CAS  Google Scholar 

  • Ezabadi IR, Camoutsis C, Zoumpoulakis P, Geronikaki A, Soković M, Glamočilija J, Cirić A (2008) Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies. Bioorg Med Chem 16:1150–1161

    Article  PubMed  CAS  Google Scholar 

  • Giraud F, Guillon R, Logé C, Pagniez F, Picot C, Le Borgne M, Le Pape P (2008) Design, synthesis, and evaluation of 1-(N-benzylamino)-2-phenyl-3(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents. Bioorg Med Chem Lett 18:1820–1824

    Article  PubMed  CAS  Google Scholar 

  • Giraud F, Guillon R, Logé C, Pagniez F, Picot C, Le Borgne M, Le Pape P (2009) Synthesis and structure-activity relationships of 2-phenyl-1-[(pyridinyl- and piperidinylmethyl)amino]-3-(1H–1,2,4-triazol-1-yl)propan-2-ols as antifungal agents. Bioorg Med Chem Lett 19:301–304

    Article  PubMed  CAS  Google Scholar 

  • Gupta A, Unadkat JD, Mao Q (2007) Interface interactions of azole antifungal agents with the human breast cancer resistance protein. J Pharm Sci 96:3226–3235

    Article  PubMed  CAS  Google Scholar 

  • Hancu G, Gaspar A, Gyeresi A (2007) Separation of 1,4-benzodiazepines by micellar electrokinetic capillary chromatography. J Biochem Biophys Methods 69:251–259

    Article  PubMed  CAS  Google Scholar 

  • Hester SD, Nesnow S (2008) Transcriptional responses in thyroid tissues from rats treated with a tumorigenic and a non-tumorigenic triazole conazole fungicide. Toxicol Appl Pharm 227:357–369

    Article  CAS  Google Scholar 

  • Holla BS, Poojary NK, Rao SB, Shivananda MK (2002) New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents. Eur J Med Chem 37:511–517

    Article  PubMed  Google Scholar 

  • Ikizler AA, Uzunali E, Demirbaş A (2000) Synthesis of some 1,2,4-triazole derivatives as potential antitumor agents. Indian J Pharm Sci 5:289–292

    Google Scholar 

  • Isloor AM, Kalluraya B, Shetty P (2009) Regioselective reaction: synthesis, characterization and pharmacological studies of some new Mannich bases derived from 1,2,4-triazoles. Eur J Med Chem 44:3784–3787

    Article  PubMed  CAS  Google Scholar 

  • Jenkins PR, Wilson J, Emmerson D, Garcia MD, Smith MR, Gray SJ, Britton RG, Mahale S, Chaudhuri B (2008) Design, synthesis and biological evaluation of new tryptamine and tetrahydro-beta-carboline-based selective inhibitors of CDK4. Bioorg Med Chem 16:7728–7739

    Article  PubMed  CAS  Google Scholar 

  • Kaplancikli ZA, Turan-Zitouni G, Ozdemir A, Revial G (2008) New triazole and triazolothiadiazine derivatives as possible antimicrobial agents. Eur J Med Chem 43:155–159

    Article  PubMed  CAS  Google Scholar 

  • Karthikeyan MK, Prasad DJ, Poojary B, Bhat KS, Holla BS, Kumari NS (2006) Synthesis and biological activity of Schiff and Mannich bases bearing 2,4-dichloro-5-fluorophenyl moiety. Bioorg Med Chem 14:7482–7489

    Article  PubMed  CAS  Google Scholar 

  • Kobeci GC, Slatford PA, Whittlesey MK, Williams JMJ (2005) N-alkylation of phenethylamine and tryptamine. Bioorg Med Chem Lett 15:535–537

    Article  Google Scholar 

  • Kuçukguzel SG, Rollas S, Erdeniz H, Kiraz M (1999) Synthesis, characterization and antimicrobial evaluation of ethyl 2-arylhydrazono-3-oxobutyrates. Eur J Med Chem 34:153–160

    Article  Google Scholar 

  • Ozdemir A, Zitouni GT, Kaplancikli ZA, Revial G, Guven K (2007) Synthesis and antimicrobial activity of 1-(4-aryl-2-thiazolyl)-3-(2-thienyl)-5-aryl-2-pyrazoline derivatives. Eur J Med Chem 42:403–409

    Article  PubMed  Google Scholar 

  • Rao BM, Sangaraju S, Srinivasu MK, Madhavan P, Devi ML, Kumar PR, Chandrasekhar KB, Arpitha C, Balaji TS (2006) Development and validation of a specific stability indicating high performance liquid chromatographic method for rizatriptan benzoate. J Pharm Biomed Anal 41:1146–1151

    Article  CAS  Google Scholar 

  • Rawal RK, Phabhakar YS, Kati SB, De Clercq E (2005) 2-(Aryl)-3-furan-2-ylmethyl-thiazolidin-4-ones as selective HIV-RT inhibitors. Bioorg Med Chem 13:6771–6776

    Article  PubMed  CAS  Google Scholar 

  • Rawal RK, Tripathi R, Kati SB, Pannecouque C, De Clercq E (2007) Design, synthesis, and evaluation of 2-aryl-3-heteroaryl-1,3-thiazolidin-4-ones as anti-HIV agents. Bioorg Med Chem 15:1725–1731

    Article  PubMed  CAS  Google Scholar 

  • Rostom SAF, Ashour HMA, Abd El Razik HA (2009) Azole antimicrobial pharmacophore-based tetrazoles: synthesis and biological evaluation as potential antimicrobial and anticonvulsant agents. Bioorg Med Chem 17:2410–2422

    Article  PubMed  CAS  Google Scholar 

  • Sahoo PK, Sharma ER, Pattanayak EP (2010) Synthesis and evaluation of 4-amino-5-phenyl-4H-[1,2,4]-triazole-3-thiol derivatives as antimicrobial agents. Med Chem Res 19:127–135

    Article  CAS  Google Scholar 

  • Sawa M, Mizuno K, Harada H, Tateishi H, Arai Y, Suzuki S, Oue M, Tsujiuchi H, Furutanic Y, Kato S (2005) Tryptamine-based human beta 3-adrenergic receptor agonists. Part 3: improved oral bioavailability via modification of the sulfonamide moiety. Bioorg Med Chem Lett 15:1061–1064

    Article  PubMed  CAS  Google Scholar 

  • Schiller SD, Fung HB (2007) Posaconazole: an extended-spectrum triazole antifungal agent. Clin Ther 29:1862–1886

    Article  PubMed  CAS  Google Scholar 

  • Solomon VR, Hua C, Lee H (2010) Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: a hybrid pharmacophore approach. Bioorg Med Chem 18:1563–1572

    Article  PubMed  CAS  Google Scholar 

  • Tozkoparan B, Gökhan N, Aktay G, Yeşilada E, Ertan M (2000) 6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones substituted with ibuprofen: synthesis, characterization and evaluation of anti-inflammatory activity. Eur J Med Chem 35:743–750

    Article  PubMed  CAS  Google Scholar 

  • Tuncbilek M, Kiper T, Altanlar N (2009) Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA. Eur J Med Chem 44:1024–1033

    Article  PubMed  CAS  Google Scholar 

  • Turan-Zitouni G, Sıvacı M, Kılıç FS, Erol K (2001) Synthesis of some triazolyl-antipyrine derivatives and investigation of analgesic activity. Eur J Med Chem 36:685–689

    Article  PubMed  CAS  Google Scholar 

  • Weidinger-Wells MA, Boggs CM, Foleno BD, Melton J, Bush K, Goldschmidt RM, Hlasta DJ (2002) Novel piperidinyloxy oxazolidinone antibacterial agents. Diversification of the N-substituent. Bioorg Med Chem 10:2345–2351

    Article  Google Scholar 

  • Yamazaki Y, Kawano Y, Yamanaka A, Maruyama S (2009) N-[(Dihydroxyphenyl)acyl]serotonins as potent inhibitors of tyrosinase from mouse and human melanoma cells. Bioorg Med Chem Lett 19:4178–4182

    Article  PubMed  CAS  Google Scholar 

  • Yu LT, Ho MT, Chang CY, Yang TK (2007) Asymmetric zinc-Reformatsky reaction of Evans chiral imide with acetophenones and its application to the stereoselective synthesis of triazole antifungal agents. Tetrahedron 18:949–962

    Article  CAS  Google Scholar 

  • Yuksek H, Demirbaş A, Ikizler A, Johansson CB, Çelik C, Ikizler AA (1997) Synthesis and antibacterial activities of some 4,5-dihydro-1H-1,2,4-triazol-5-ones. Arzn-Forsh Drug Res 47:405–409

    CAS  Google Scholar 

Download references

Acknowledgments

This project was supported by Scientific and Technological Research Council of Turkey (TUBITAK, Project no: 107T333) and Karadeniz Technical University, BAP, Turkey (Ref. No. 2007.111.002.6) and is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Sciences, Giresun University, 28100, Giresun, Turkey

    Hakan Bektas

  2. Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, 61080, Trabzon, Turkey

    Ahmet Demirbas & Neslihan Demirbas

  3. Department of Biology, Faculty of Sciences, Rize University, 53100, Rize, Turkey

    Sengul Alpay Karaoglu

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  1. Hakan Bektas
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  2. Ahmet Demirbas
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  3. Neslihan Demirbas
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  4. Sengul Alpay Karaoglu
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Correspondence to Neslihan Demirbas.

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Bektas, H., Demirbas, A., Demirbas, N. et al. Synthesis and biological activity studies of new hybrid molecules containing tryptamine moiety. Med Chem Res 21, 212–223 (2012). https://doi.org/10.1007/s00044-010-9531-y

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  • DOI: https://doi.org/10.1007/s00044-010-9531-y

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