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Current Cancer Therapy Reviews

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ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

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Review Article

Triazole as Potent Anti-cancer Agent- A Pharmacophoric Scaffold

Author(s): Nidhi Kala* and Kalpana Praveen Rahate

Volume 18, Issue 2, 2022

Published on: 14 January, 2022

Page: [95 - 117] Pages: 23

DOI: 10.2174/1573394717666211006102147

Price: $65

Abstract

Triazole is the main five-membered Nitrogen-containing basic heterocyclic ring system reported for their biological activities and compounds with multiple pharmacophores, which fetch together acquaintance of a target with sympathetic types of the molecule that might interact with the target. In addition, healthy, adaptable, and scalable chemistry must be employed to achieve the task. This characteristic feature of triazole would make a good template for a lead cohort library. The current review article focuses on recent advancements in triazole moiety as an anti-cancer agent with their mechanism pathways of synthesized analogues.

Keywords: Cytotoxicity, anti-proliferation, MTT assay, click chemistry, caspase-3, 7 and 9, topoisomerase, apoptosis.

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[1]
Alraqa SY, Alharbi K, Aljuhani A, Rezki N, Aouad MR, Ali I. Design, click conventional and microwave syntheses, DNA binding, docking and anti-cancer studies of benzotriazole-1, 2, 3-triazole molecular hybrids with different pharmacophores. J Mol Struct 2020; 129: 192-202.
[2]
Slaihim MM, Al-Suede FS, Khairuddean M, Ahamed MB, Majid AM. Synthesis, characterization of new derivatives with mono ring system of 1, 2, 4-triazole scaffold, and their anti-cancer activities. J Mol Struct 2019; 1196: 78-87.
[http://dx.doi.org/10.1016/j.molstruc.2019.06.066]
[3]
El-Sherief HAM, Youssif BGM, Abbas Bukhari SN, Abdelazeem AH, Abdel-Aziz M, Abdel-Rahman HM. Synthesis, anticancer activity and molecular modeling studies of 1,2,4-triazole derivatives as EGFR inhibitors. Eur J Med Chem 2018; 156: 774-89.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.024] [PMID: 30055463]
[4]
Zhang B. Comprehensive review on the anti-bacterial activity of 1,2,3-triazole hybrids. Eur J Med Chem 2019; 168: 357-72.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.055] [PMID: 30826511]
[5]
Dheer D, Singh V, Shankar R. Medicinal attributes of 1,2,3-triazoles: Current developments. Bioorg Chem 2017; 71: 30-54.
[http://dx.doi.org/10.1016/j.bioorg.2017.01.010] [PMID: 28126288]
[6]
Lal K, Yadav P. Recent advancements in 1, 4-disubstituted 1H-1, 2, 3-triazoles as potential anti-cancer agents. Anti-cancer agents in medicinal chemistry (formerly current medicinal chemistry-anti-cancer agents) 2018; 18(1): 21-37.
[7]
Akhtar J, Khan AA, Ali Z, Haider R, Shahar Yar M. Structure-activity relationship (SAR) study and design strategies of nitrogen- containing heterocyclic moieties for their anticancer activities. Eur J Med Chem 2017; 125: 143-89.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.023] [PMID: 27662031]
[8]
Emami S, Ghobadi E, Saednia S, Hashemi SM. Current advances of triazole alcohols derived from fluconazole: Design, in vitro and in silico studies. Eur J Med Chem 2019; 170: 173-94.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.020] [PMID: 30897396]
[9]
Victoria Castelli M, Gabriel Derita M, Noelí López S. Novel antifungal agents: A patent review (2013 - present). Expert Opin Ther Pat 2017; 27(4): 415-26.
[http://dx.doi.org/10.1080/13543776.2017.1261113] [PMID: 27897041]
[10]
Tian Y, Liu Z, Liu J, et al. Targeting the entrance channel of NNIBP: Discovery of diarylnicotinamide 1,4-disubstituted 1,2,3- triazoles as novel HIV-1 NNRTIs with high potency against wild- type and E138K mutant virus. Eur J Med Chem 2018; 151: 339-50.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.059] [PMID: 29635166]
[11]
Kaoukabi H, Kabri Y, Curti C, et al. Dihydropyrimidinone/1,2,3- triazole hybrid molecules: Synthesis and anti-varicella-zoster virus (VZV) evaluation. Eur J Med Chem 2018; 155: 772-81.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.028] [PMID: 29945100]
[12]
Zhang S, Xu Z, Gao C, et al. Triazole derivatives and their anti-tubercular activity. Eur J Med Chem 2017; 138: 501-13.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.051] [PMID: 28692915]
[13]
Keri RS, Patil SA, Budagumpi S, Nagaraja BM. Triazole: A promising antitubercular agent. Chem Biol Drug Des 2015; 86(4): 410-23.
[http://dx.doi.org/10.1111/cbdd.12527] [PMID: 25643871]
[14]
Chu XM, Wang C, Wang WL, et al. Triazole derivatives and their antiplasmodial and antimalarial activities. Eur J Med Chem 2019; 166: 206-23.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.047] [PMID: 30711831]
[15]
Kalaria PN, Karad SC, Raval DK. A review on diverse heterocyclic compounds as the privileged scaffolds in antimalarial drug discovery. Eur J Med Chem 2018; 158: 917-36.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.040] [PMID: 30261467]
[16]
Djemoui A, Naouri A, Ouahrani MR, et al. A step-by-step synthesis of triazole-benzimidazole-chalcone hybrids: Anti-cancer activity in human cells+. J Mol Struct 2020; 1204: 127487-97.
[http://dx.doi.org/10.1016/j.molstruc.2019.127487]
[17]
Muniyappan G, Kathavarayan S, Balachandran C, et al. Synthesis, anticancer and molecular docking studies of new class of benzoisoxazolyl-piperidinyl-1, 2, 3-triazoles. J King Saud Univ Sci 2020; 32(8): 3286-92.
[http://dx.doi.org/10.1016/j.jksus.2020.09.012]
[18]
Gurrapu N, Kumar EP, Kolluri PK, Putta S, Sivan SK, Subhashini NJ. Synthesis, biological evaluation and molecular docking studies of novel 1, 2, 3-triazole tethered chalcone hybrids as potential anti-cancer agents. J Mol Struct 2020; 128356-67.
[http://dx.doi.org/10.1016/j.molstruc.2020.128356]
[19]
Madasu C, Karri S, Sangaraju R, Sistla R, Uppuluri MV. Synthesis and biological evaluation of some novel 1,2,3-triazole hybrids of myrrhanone B isolated from Commiphora mukul gum resin: Identification of potent antiproliferative leads active against prostate cancer cells (PC-3). Eur J Med Chem 2020; 188: 111974-2025.
[http://dx.doi.org/10.1016/j.ejmech.2019.111974] [PMID: 31883489]
[20]
Ashour HF, Abou-Zeid LA, El-Sayed MA, Selim KB. 1,2,3-Triazole-Chalcone hybrids: Synthesis, in vitro cytotoxic activity and mechanistic investigation of apoptosis induction in multiple myeloma RPMI-8226. Eur J Med Chem 2020; 189: 112062-75.
[http://dx.doi.org/10.1016/j.ejmech.2020.112062] [PMID: 31986406]
[21]
Tan A. Novel 1, 2, 3-triazole compounds: Synthesis, In vitro xanthine oxidase inhibitory activity, and molecular docking studies. J Mol Struct 2020; 128060-8.
[http://dx.doi.org/10.1016/j.molstruc.2020.128060]
[22]
Aouad MR, Almehmadi MA, Rezki N, Al-blewi FF, Messali M, Ali I. Design, click synthesis, anti-cancer screening and docking studies of novel benzothiazole-1, 2, 3-triazoles appended with some bioactive benzofused heterocycles. J Mol Struct 2019; 1188: 153-64.
[http://dx.doi.org/10.1016/j.molstruc.2019.04.005]
[23]
Fu DJ, Li P, Wu BW, Cui XX, Zhao CB, Zhang SY. Molecular diversity of trimethoxyphenyl-1,2,3-triazole hybrids as novel colchicine site tubulin polymerization inhibitors. Eur J Med Chem 2019; 165: 309-22.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.033] [PMID: 30690300]
[24]
Aneja B, Khan NS, Khan P, et al. Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis. Eur J Med Chem 2019; 163: 840-52.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.026] [PMID: 30579124]
[25]
Zhao JW, Wu ZH, Guo JW, et al. Synthesis and anti-gastric cancer activity evaluation of novel triazole nucleobase analogues containing steroidal/coumarin/quinoline moieties. Eur J Med Chem 2019; 181: 111520-32.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.023] [PMID: 31404863]
[26]
Macan AM, Harej A, Cazin I, et al. Antitumor and antiviral activities of 4-substituted 1,2,3-triazolyl-2,3-dibenzyl-L-ascorbic acid derivatives. Eur J Med Chem 2019; 184: 111739-55.
[http://dx.doi.org/10.1016/j.ejmech.2019.111739] [PMID: 31586832]
[27]
Murugavel S, Ravikumar C, Jaabil G, Alagusundaram P. Synthesis, crystal structure analysis, spectral investigations (NMR, FT-IR, UV), DFT calculations, ADMET studies, molecular docking and anti-cancer activity of 2-(1-benzyl-5-methyl-1H-1, 2, 3-triazol-4-yl)-4-(2-chlorophenyl)-6-methoxypyridine–a novel potent human topoisomerase IIα inhibitor. J Mol Struct 2019; 1176: 729-42.
[http://dx.doi.org/10.1016/j.molstruc.2018.09.010]
[28]
Allam M, Bhavani AKD, Mudiraj A, Ranjan N, Thippana M, Babu PP. Synthesis of pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazoles and their evaluation as potential anticancer agents. Eur J Med Chem 2018; 156: 43-52.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.055] [PMID: 30006173]
[29]
Aboeldahab AMA, Beshr EAM, Shoman ME, Rabea SM, Aly OM. Spirohydantoins and 1,2,4-triazole-3-carboxamide derivatives as inhibitors of histone deacetylase: Design, synthesis, and biological evaluation. Eur J Med Chem 2018; 146: 79-92.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.021] [PMID: 29396364]
[30]
Ahmed FF, Abd El-Hafeez AA, Abbas SH, Abdelhamid D, Abdel-Aziz M. New 1,2,4-triazole-Chalcone hybrids induce Caspase-3 dependent apoptosis in A549 human lung adenocarcinoma cells. Eur J Med Chem 2018; 151: 705-22.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.073] [PMID: 29660690]
[31]
Costa DCS, de Almeida GS, Rabelo VW, et al. Synthesis and evaluation of the cytotoxic activity of Furanaphthoquinones tethered to 1H-1,2,3-triazoles in Caco-2, Calu-3, MDA-MB231 cells. Eur J Med Chem 2018; 156: 524-33.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.018] [PMID: 30025347]
[32]
Ke Y, Liang JJ, Hou RJ, et al. Synthesis and biological evaluation of novel Jiyuan Oridonin A-1,2,3-triazole-azole derivatives as antiproliferative agents. Eur J Med Chem 2018; 157: 1249-63.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.056] [PMID: 30193221]
[33]
Janganati V, Ponder J, Balasubramaniam M, et al. MMB triazole analogs are potent NF-κB inhibitors and anti-cancer agents against both hematological and solid tumor cells. Eur J Med Chem 2018; 157: 562-81.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.010] [PMID: 30121494]
[34]
Rostom SAF, Badr MH, Abd El Razik HA, Ashour HMA. Structure-based development of novel triazoles and related thiazolotriazoles as anticancer agents and Cdc25A/B phosphatase inhibitors. Synthesis, in vitro biological evaluation, molecular docking and in silico ADME-T studies. Eur J Med Chem 2017; 139: 263-79.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.053] [PMID: 28803043]
[35]
Huang M, Deng Z, Tian J, Liu T. Synthesis and biological evaluation of salinomycin triazole analogues as anticancer agents. Eur J Med Chem 2017; 127: 900-8.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.067] [PMID: 27876192]
[36]
Yadav P, Lal K, Kumar A, Guru SK, Jaglan S, Bhushan S. Green synthesis and anticancer potential of chalcone linked-1,2,3-triazoles. Eur J Med Chem 2017; 126: 944-53.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.030] [PMID: 28011424]
[37]
Lu Y, Wang L, Wang X, et al. Design, combinatorial synthesis and biological evaluations of novel 3-amino-1′-((1-aryl-1H-1,2,3- triazol-5-yl)methyl)-2′-oxospiro[benzo[a] pyrano[2,3-c]phenazine-1,3′-indoline]-2-carbonitrile antitumor hybrid molecules. Eur J Med Chem 2017; 135: 125-41.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.040] [PMID: 28441581]
[38]
Shaik SP, Vishnuvardhan MVPS, Sultana F, et al. Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors. Bioorg Med Chem 2017; 25(13): 3285-97.
[http://dx.doi.org/10.1016/j.bmc.2017.04.013] [PMID: 28462842]
[39]
Su CL, Tseng CL, Ramesh C, Liu HS, Huang CF, Yao CF. Using gene expression database to uncover biology functions of 1,4-disubstituted 1,2,3-triazole analogues synthesized via a copper (I)-catalyzed reaction. Eur J Med Chem 2017; 132: 90-107.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.034] [PMID: 28342400]
[40]
Ruddarraju RR, Murugulla AC, Kotla R, et al. Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives. Eur J Med Chem 2016; 123: 379-96.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.024] [PMID: 27487568]
[41]
Kraljević TG, Harej A, Sedić M, et al. Synthesis, in vitro anticancer and antibacterial activities and in silico studies of new 4- substituted 1,2,3-triazole-coumarin hybrids. Eur J Med Chem 2016; 124: 794-808.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.062] [PMID: 27639370]
[42]
Kulabaş N, Tatar E, Bingöl Özakpınar Ö, et al. Synthesis and antiproliferative evaluation of novel 2-(4H-1,2,4-triazole-3-ylthio)acetamide derivatives as inducers of apoptosis in cancer cells. Eur J Med Chem 2016; 121: 58-70.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.017] [PMID: 27214512]
[43]
Khan I, Guru SK, Rath SK, et al. A novel triazole derivative of betulinic acid induces extrinsic and intrinsic apoptosis in human leukemia HL-60 cells. Eur J Med Chem 2016; 108: 104-16.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.018] [PMID: 26629862]
[44]
Li ZH, Yang DX, Geng PF, et al. Design, synthesis and biological evaluation of [1,2,3]triazolo[4,5-d]pyrimidine derivatives possessing a hydrazone moiety as antiproliferative agents. Eur J Med Chem 2016; 124: 967-80.
[http://dx.doi.org/10.1016/j.ejmech.2016.10.022] [PMID: 27771599]
[45]
Praveen Kumar C, Reddy TS, Mainkar PS, et al. Synthesis and biological evaluation of 5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one structural derivatives as anti-cancer and apoptosis inducing agents. Eur J Med Chem 2016; 108: 674-86.
[http://dx.doi.org/10.1016/j.ejmech.2015.12.007] [PMID: 26735909]
[46]
Sever B, Altıntop MD, Kuş G, Özkurt M, Özdemir A, Kaplancıklı ZA. Indomethacin based new triazolothiadiazine derivatives: Synthesis, evaluation of their anticancer effects on T98 human glioma cell line related to COX-2 inhibition and docking studies. Eur J Med Chem 2016; 113: 179-86.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.036] [PMID: 26927686]
[47]
Shaik SP, Nayak VL, Sultana F, et al. Design and synthesis of imidazo[2,1-b]thiazole linked triazole conjugates: Microtubule-destabilizing agents. Eur J Med Chem 2017; 126: 36-51.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.060] [PMID: 27744185]
[48]
Ashwini N, Garg M, Mohan CD, et al. Synthesis of 1,2-benzisoxazole tethered 1,2,3-triazoles that exhibit anticancer activity in acute myeloid leukemia cell lines by inhibiting histone deacetylases, and inducing p21 and tubulin acetylation. Bioorg Med Chem 2015; 23(18): 6157-65.
[http://dx.doi.org/10.1016/j.bmc.2015.07.069] [PMID: 26299825]
[49]
Senwar KR, Sharma P, Reddy TS, et al. Spirooxindole-derived morpholine-fused-1,2,3-triazoles: Design, synthesis, cytotoxicity and apoptosis inducing studies. Eur J Med Chem 2015; 102: 413-24.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.017] [PMID: 26301558]
[50]
Madadi NR, Penthala NR, Howk K, et al. Synthesis and biological evaluation of novel 4,5-disubstituted 2H-1,2,3-triazoles as cis- constrained analogues of combretastatin A-4. Eur J Med Chem 2015; 103: 123-32.
[http://dx.doi.org/10.1016/j.ejmech.2015.08.041] [PMID: 26352674]
[51]
Lipeeva AV, Pokrovsky MA, Baev DS, et al. Synthesis of 1H-1,2,3-triazole linked aryl(arylamidomethyl) - dihydrofurocoumarin hybrids and analysis of their cytotoxicity. Eur J Med Chem 2015; 100: 119-28.
[http://dx.doi.org/10.1016/j.ejmech.2015.05.016] [PMID: 26079088]
[52]
Kandeel MM, Refaat HM, Kassab AE, Shahin IG, Abdelghany TM. Synthesis, anticancer activity and effects on cell cycle profile and apoptosis of novel thieno[2,3-d]pyrimidine and thieno[3,2-e] triazolo[4,3-c]pyrimidine derivatives. Eur J Med Chem 2015; 90: 620-32.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.009] [PMID: 25499930]
[53]
De Lucia D, Lucio OM, Musio B, et al. Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors. Eur J Med Chem 2015; 101: 573-83.
[http://dx.doi.org/10.1016/j.ejmech.2015.07.011] [PMID: 26197161]

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