Abstract
A 60-member 1,2,3-triazoles bearing biologically active sulfonamide moiety library was synthesized via azide–alkyne cycloaddition and examined for cytotoxic activity against human leukemia cell line HL-60. 25 of them were evaluated further in four additional cancer cell lines (HepG2, A549, PC3, SGC7901). Most of the 25 compounds showed moderate cytotoxic activities against the tested cell lines. Furthermore, the structure–activity relationships were discussed and a reliable 3D-QSAR model with good prediction \({\left(r_{\rm cv}^{2 } = 0.64, r^{2} = 0.958\right)}\) was generated on the basis of our synthesized 1,2,3-triazoles for their cytotoxic activities against the HL-60 cell line. The contour map of the CoMFA should aid in the design of new antitumor agents.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Jordão AK, Afonso PP, Ferreira VF, de Souza MC, Almeida MC, Beltrame CO, Paiva DP, Wardell SM, Wardell JL, Tiekink ER, Damaso CR, Cunha AC (2009) Antiviral evaluation of N-amino-1,2,3-triazoles against Cantagalo virus replication in cell culture. Eur J Med Chem 44: 3777–3783 doi:10.1016/j.ejmech.2009.04.046
Chaudhary PM, Chavan SR, Shirazi F, Razdan M, Nimkar P, Maybhate SP, Likhite AP, Gonnade R, Hazara BG, Deshpande MV, Deshpande SR (2009) Exploration of click reaction for the synthesis of modified nucleosides as chitin synthase inhibitors. Bioorg Med Chem 17: 2433–2440 doi:10.1016/j.bmc.2009.02.019
Chen H, Taylor JL, Abrams SR (2007) Design and synthesis of beta-methoxyacrylate analogues via click chemistry and biological evaluations. Bioorg Med Chem 17: 1979–1983 10.1016/j.bmcl.2007.01.021
Tripathi RP, Yadav AK, Ajay A, Bisht SS, Chaturvedi V, Sinha SK (2010) Application of Huisgen (3+2) cycloaddition reaction: synthesis of 1-(2,3-dihydrobenzofuran-2-yl-methyl [1,2,3]-triazoles and their antitubercular evaluations. Eur J Med Chem 45: 142–148 doi:10.1016/j.ejmech.2009.09.036
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 18: 1468–1473 doi:10.1016/j.bmcl.2007.12.063
Pagliai F, Pirali T, Del Grosso E, Di Brisco R, Tron GC, Sorba G, Genazzani AA (2006) Rapid synthesis of triazole-modified resveratrol analogues via click chemistry. J Med Chem 49: 467–470 doi:10.1021/jm051118z
de las Heras FG, Alonso R, Alonso G (1979) Alkylating nucleosides 1. Synthesis and cytostatic activity of N-glycosyl(halomethyl)-1,2,3-triazoles. A new type of alkylating agent. J Med Chem 22: 496–501 doi:10.1021/jm00191a007
Trabocchi A, Menchi G, Cini N, Bianchini F, Raspanti S, Bottoncetti A, Pupi A, Calorini L, Guarna A (2010) Click-chemistry-derived triazole ligands of arginine-glycine-aspartate (RGD) integrins with a broad capacity to inhibit adhesion of melanoma cells and both in vitro and in vivo angiogenesis. J Med Chem 53: 7119–7128 doi:10.1021/jm100754z
Alqasoumi SI, Al-Taweel AM, Alafeefy AM, Noaman E, Ghorab MM (2010) Novel quinolines and pyrimido[4,5-b]quinolines bearing biologically active sulfonamide moiety as a new class of antitumor agents. Eur J Med Chem 45: 738–744 doi:10.1016/j.ejmech.2009.11.021
Rostom SA (2006) Synthesis and in vitro antitumor evaluation of some indeno[1,2-c]pyrazol(in)es substituted with sulfonamide, sulfonylurea(-thiourea) pharmacophores, and some derived thiazole ring systems. Bioorg Med Chem 14: 6475–6485 doi:10.1016/j.bmc.2006.06.020
Supuran CT, Casini A, Mastrolorenzo A, Scozzafava A (2004) COX-2 selective inhibitors, carbonic anhydrase inhibition and anticancer properties of sulfonamides belonging to this class of pharmacological agents. Mini Rev Med Chem 4: 625–632
Abbate F, Casini A, Owa T, Scozzafava A, Supuran CT (2004) Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg Med Chem Lett 14: 217–223 doi:10.1016/j.bmcl.2003.09.062
Gandon LA, Russell AG, Güveli T, Brodwolf AE, Kariuki BM, Spencer N, Snaith JS (2006) Synthesis of 2,4-disubstituted piperidines via radical cyclization: unexpected enhancement in diastereoselectivity with tris(trimethylsilyl)silane. J Org Chem 71: 5198–5207 doi:10.1021/jo060495w
Whiting M, Tripp JC, Lin YC, Lindstrom W, Olson AJ, Elder JH, Sharpless KB, Fokin VV (2006) Rapid discovery and structure–activity profiling of novel inhibitors of human immunodeficiency virus type 1 protease enabled by the copper(I)-catalyzed synthesis of 1,2,3-triazoles and their further functionalization. J Med Chem 49: 7697–7710 doi:10.1021/jm060754+
Hu MK, Liao YF, Chen JF, Wang BJ, Tung YT, Lin HC, Lee KP (2008) New 1,2,3,4-tetrahydroisoquinoline derivatives as modulators of proteolytic cleavage of amyloid precursor proteins. Bioorg Med Chem 16: 1957–1965 doi:10.1016/j.bmc.2007.10.101
Bombrun A (1997) Carboline derivatives. Patent No. WO97/43287
Lodewijk E, Khatri HN (1990) 2-(2-nitrovinyl)thiophene reduction and synthesis of thieno[3,2-c]pyridine derivatives. Patent No. US4906756
Bobbitt JM, Kiely JM, Khanna KL, Ebermann R (1965) Synthesis of isoquinolines. III. A new synthesis of 1,2,3,4-tetrahydroisoquinolines. J Org Chem 30: 2247–2250 10.1021/jo01018a030
Wu B, Xia L, Jiang Z (2003) Synthesis and biological activities of N-(5-methoxy-1H-indole-3-ethy1)-4-subtituted phenyIpiperazine-1-acetic amide derivatives as α1-adrenoceptor antagonists. J China Pharma Univ 34: 391–395
Jain PC, Kapoor V, Anand N, Ahmad A, Patnaik GK (1967) Compounds acting on the central nervous system. VII. Studies in 1-pyridyl-4-substituted piperazines. A new class of anticonvulsants. J Med Chem 10: 812–818 doi:10.1021/jm00317a013
Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed 41:2596-2599 doi:10.1002/1521-3773 (20020715)
(2001) Sybyl molecular modeling software packages, 6.9; TRIPOS Associates, Inc., St Louis, MO63114
Chen JZ, Han XW, Liu Q, Makriyannis A, Wang J, Xie XQ (2006) 3D-QSAR studies of arylpyrazole antagonists of cannabinoid receptor subtypes CB1 and CB2. A combined NMR and CoMFA approach. J Med Chem 49: 625–636 doi:10.1021/jm050655g
Xie XQ, Han XW, Chen JZ, Eissenstat M, Makriyannis A (1999) High-resolution NMR and computer modeling studies of the cannabimimetic aminoalkylindole prototype WIN-55212-2. J Med Chem 42: 4021–4027 doi:10.1021/jm980592k
Dunn WJ III, Wold S, Edlund U, Hellberg S, Gasteiger J (1984) Multivariate structure–activity relationships between data from a battery of biological tests and an ensemble of structure descriptors: the PLS method. Quant Struct Act Relat 3: 131–137
Kubinyi H (1998) The encyclopedia of computational chemistry. Wiley, Chichester
Author information
Authors and Affiliations
Corresponding authors
Additional information
Lili Ou and Shuang Han contributed equally to this work.
Electronic Supplementary Material
The Below is the Electronic Supplementary Material.
Rights and permissions
About this article
Cite this article
Ou, L., Han, S., Ding, W. et al. Parallel synthesis of novel antitumor agents: 1,2,3-triazoles bearing biologically active sulfonamide moiety and their 3D-QSAR. Mol Divers 15, 927–946 (2011). https://doi.org/10.1007/s11030-011-9324-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11030-011-9324-3