Review
Synthetic and Medicinal Perspective of 1,2,4-Triazole as Anticancer Agents
Bhagyashri Rathod,
Kapil Kumar,
Bhagyashri Rathod
School of Pharmacy and Technology Management, SVKM's NMIMS, Hyderabad, Telangana, 509301 India
Search for more papers by this authorCorresponding Author
Kapil Kumar
School of Pharmacy and Technology Management, SVKM's NMIMS, Hyderabad, Telangana, 509301 India
School of Pharmaceutical Sciences, Apeejay Stya University, Gurugram, Haryana, 122103 India
Search for more papers by this authorBhagyashri Rathod,
Kapil Kumar,
Bhagyashri Rathod
School of Pharmacy and Technology Management, SVKM's NMIMS, Hyderabad, Telangana, 509301 India
Search for more papers by this authorCorresponding Author
Kapil Kumar
School of Pharmacy and Technology Management, SVKM's NMIMS, Hyderabad, Telangana, 509301 India
School of Pharmaceutical Sciences, Apeejay Stya University, Gurugram, Haryana, 122103 India
Search for more papers by this authorAbstract
Cancer is still one of the leading causes of death worldwide. Many researchers are working to design and develop heterocyclic-based drugs with the potential to treat cancer at various stages. There is always an unmet need to discover new anticancer drugs to treat different types of cancer. Based on literature reports, it was evident that hybrid 1,2,4-triazoles exhibit a wide spectrum of biological potential (particularly potent anticancer activity), as compared to the corresponding monocyclic compounds. In this review, we summarized fused/hybrid 1,2,4-triazole and poly-functionalized 1,2,4-triazoles as anticancer agents. Triazole may be fused with other heterocyclic scaffolds like pyrimidine, pyridine, piperidine, quinoxaline, quinazoline, thiadiazine, indole, phthalazine etc. A clear explanation of the method of synthesis, structure-activity relationship, and in vitro results plus the inhibitory concentration of new molecules are focused on in this review article.
Graphical Abstract
Conflict of interest
Authors declare no conflict of interest for this article.
Open Research
Data Availability Statement
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
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- 80Y. Li, Y. He, T. Shao, H. Pei, W. Guo, D. Mi, I. Krimm, Y. Zhang, P. Wang, X. Wang, M. Liu, ‘Modification and Biological Evaluation of a Series Of 1, 5-Diaryl-1, 2, 4-Triazole Compounds as Novel Agents Against Pancreatic Cancer Metastasis Through Targeting Myoferlin’, J. Med. Chem. 2019, 62, 4949–4966.
- 81Z. Wu, X. Li, C. L. Chi, L. Xu, Y. Y. Sun, B. Q. Chen, ‘Synthesis and Antitumor Effects of a New Class Of 1, 2, 4-Triazole Derivatives’, Med. Chem. Res. 2021, 30, 142–151.
- 82N. Li, C. Chen, Z. Shi, J. Sun, L. Chen, ‘Discovery of Novel Celastrol-Triazole Derivatives with Hsp90-Cdc37 Disruption to Induce Tumor Cell Apoptosis’, Bioorg. Chem. 2021, 111, 104867.
- 83A. E. Nofal, I. M. Shatla, D. A. Abdelhafeez, M. Mustafa, O. M. Aly, ‘OMA1520 and OMA1774, Novel 1, 2, 4-Triazole Bearing Analogs of Combretastatin A-4, Inhibit Hepatocellular Carcinoma: Histological and Immunohistochemical Studies’, Biomed. Pharmacother. 2021, 138, 111417.
- 84M. Mustafa, S. Anwar, F. Elgamal, E. R. Ahmed, O. M. Aly, ‘Potent Combretastatin A-4 Analogs Containing 1, 2, 4-Triazole: Synthesis, Antiproliferative, Anti-Tubulin Activity, and Docking Study’, Eur. J. Med. Chem. 2019, 183, 111697.
- 85K. Birgul, Y. Yıldırım, H. Y. Karasulu, E. Karasulu, A. I. Uba, K. Yelekci, H. Bekci, A. Cumaoglu, L. Kabasakal, O. Yılmaz, S. G. Kuçukguzel, ‘Synthesis, Molecular Modeling, in vivo Study and Anticancer Activity Against Prostate Cancer Of (+) (S)-Naproxen Derivatives’, Eur. J. Med. Chem. 2020, 208, 112841.
- 86K. Kumar, R. K. Rawal, ‘Cui/DBU-Mediated MBH Reaction of Isatins: A Convenient Synthesis Of 3-Substituted-3-Hydroxy-2-Oxindole’, ChemistrySelect 2020, 5, 3048–3051.
- 87R. Kaur, K. Kumar, ‘One-Pot Synthesis Of [4-(Tert-Butyl)-1H-Pyrrol-3-Yl] (Phenyl)Methanone from Tosylmethyl Isocyanide and Carbonyl Compound’, Chem. Heterocycl. Compd. 2018, 54, 700–702.
- 88K. Kumar, S. S. More, G. L. Khatik, R. K. Rawal, V. A. Nair, ‘A Highly Stereoselective Chiral Auxiliary-Assisted Reductive Cyclization to Furoindoline’, J. Heterocycl. Chem. 2017, 54, 2696–2702.
- 89K. Kumar, D. Konar, S. Goyal, M. Gangar, M. Chouhan, R. K. Rawal, V. A. Nair, ‘Water Promoted Regiospecific Azidolysis and Copper Catalysed Azide Alkyne Cycloaddition: One-Pot Synthesis Of 3-Hydroxy-1-Alkyl-3-[(4-Aryl/Alkyl-1H-1,2,3-Triazol-1-Yl) Methyl] Indolin-2-One Derivatives’, J. Org. Chem. 2016, 81, 9757–9764.
- 90K. Kumar, J. Siddique, M. Gangar, S. Goyal, R. K. Rawal, V. A. Nair, ‘ZrCl4 Catalysed Diastereoselective Synthesis of Spirocarbocyclic Oxindoles Via [4+2] Cycloaddition’, ChemistrySelect 2016, 1, 2409–2412.
- 91K. Kumar, D. Konar, S. Goyal, M. Gangar, M. Chouhan, R. K. Rawal, V. A. Nair, ‘AlCl3/Cyclohexane Mediated Electrophilic Activation of Isothiocyanates: An Efficient Synthesis of Thioamides’, ChemistrySelect 2016, 1, 3228–3231.
- 92K. Kumar, S. S. More, S. Goyal, M. Gangar, G. L. Khatik, R. K. Rawal, V. A. Nair, ‘A Convenient Synthesis Of 4-Alkyl-3-Benzyolpyrroles From Α, Β-Unsaturated Ketone and Tosylmethylisocyanide’, Tetrahedron Lett. 2016, 57, 2315–2319.
- 93K. Kumar, S. R. Mudshinge, S. Goyal, M. Gangar, V. A. Nair, ‘A Catalyst Free, One Pot Approach for The Synthesis of Quinoxaline Derivatives Via Oxidative Cyclization Of 1,2-Diamines and Phenacyl Bromides’, Tetrahedron Lett. 2015, 56, 1266–1271.
- 94S. Goyal, J. K. Patel, M. Gangar, K. Kumar, V. A. Nair, ‘Zirconocene Dichloride Catalysed One-Pot Synthesis of Pyrroles Through Nitroalkene-Enamine Assembly’, RSC Adv. 2015, 5, 3187–3195.
- 95S. Goyal, B. K. Patel, R. Sharma, M. Chouhan, K. Kumar, M. Gangar, V. A. Nair, ‘An Efficient Strategy for The Synthesis of Syn 1,3-Diols Via Iterative Acetate Aldol Reactions and Synthesis of Atorvastatin Lactone’, Tetrahedron Lett. 2015, 56, 5409–5412.
- 96M. Gangar, N. Kashyap, K. Kumar, S. Goyal, V. A. Nair, ‘Imidazolidinone Based Chiral Auxiliary Mediated Acetate Aldol Reactions of Isatin Derivatives and Stereoselective Synthesis Of 3-Substituted-3-Hydroxy-2-Oxindoles’, Tetrahedron Lett. 2015, 56, 7074–7081.
- 97M. Chouhan, K. R. Senwar, K. Kumar, R. Sharma, V. A. Nair, ‘Catalytic C−H Activation of Arylacetylenes: A Fast Assembly Of 3-Hydroxy-3-(Arylethynyl) Indolin-2-Ones Using Cui/DBU’, Synthesis 2014, 46, 195–202.
- 98V. Kumar, K. Kumar, A. Pal, G. L. Khatik, V. A. Nair, ‘Aldol Reactions Of 2-Thioxotetrahydropyrimidin-4(1H)-Ones: Stereoregulations from Endo- and Exo-Cyclic Chiral Centres’, Tetrahedron 2013, 69, 1747–1754.
- 99R. Sharma, K. Kumar, M. Chouhan, V. Grover, V. A. Nair, ‘Lithium Hydroxide Mediated Synthesis Of 3,4-Disubstituted Pyrroles’, RSC Adv. 2013, 3, 14521–14527.
- 100M. Chouhan, K. Kumar, R. Sharma, V. Grover, V. A. Nair, ‘Nicl2.H2O/Nabh4 in Methanol: A Mild and Efficient Strategy for Chemoselective Deallylation/Debenzylation of Aryl Ethers’, Tetrahedron Lett. 2013, 54, 4540–4543.
- 101K. Kumar, ‘Microwave Assisted Diversified Synthesis of Pyrimidines: An Overview’, J. Heterocycl. Chem. 2022, 59, 205–238.
- 102D. Konar, S. Maru, S. Kar, K. Kumar, ‘Synthesis and Clinical Development of Palbociclib: An Overview’, Med. Chem. 2022, 18, 2–25.
- 103S. Pawar, K. Kumar, M. K. Gupta, R. K. Rawal, ‘Synthetic and Medicinal Perspective of Fused-Thiazoles as Anticancer Agents’, Anti-Cancer Agents Med. Chem. 2021, 21, 1379–1402.
- 104R. Kaur, K. Kumar, ‘Synthetic and Medicinal Perspective of Quinolines as Antiviral Agents’, Eur. J. Med. Chem. 2021, 215, 113220–113258.
- 105K. Kumar, ‘TosMIC: A Powerful Synthon for Cyclization and Sulfonylation’, ChemistrySelect 2020, 5, 10298–10328.
- 106Y. Kapoor, K. Kumar, ‘Structural and Clinical Impact of Anti-Allergy Agents: An Overview’, Bioorg. Chem. 2020, 54, 103351–103375.
- 107R. Kaur, Y. Kapoor, S. K. Manjal, R. K. Rawal, K. Kumar, ‘Diversity-Oriented Synthetic Approaches for Furoindoline: A Review’, Curr. Org. Synth. 2019, 16, 342–368.
- 108S. K. Manjal, S. Pathania, R. Bhatia, R. Kaur, K. Kumar, R. K. Rawal, ‘Diversified Synthetic Strategies for Pyrroloindoles: An Overview’, J. Heterocycl. Chem. 2019, 56, 2318–2332.
- 109R. Kaur, S. K. Manjal, R. K. Rawal, K. Kumar, ‘Recent Synthetic and Medicinal Perspective of Tryptanthrin’, Bioorg. Med. Chem. 2017, 25, 4533–4552.
- 110S. K. Manjal, R. Kaur, R. Bhatia, K. Kumar, V. Singh, R. Shankar, R. Kaur, R. K. Rawal, ‘Synthetic and Medicinal Perspective of Thiazolidinones: A Review’, Bioorg. Chem. 2017, 75, 406–423.
- 111R. Kaur, S. Chaudhary, K. Kumar, M. K. Gupta, R. K. Rawal, ‘Recent Synthetic and Medicinal Perspectives of Dihydropyrimidinones: A Review’, Eur. J. Med. Chem. 2017, 132, 108–134.
- 112B. Kumar, V. Singh, R. Shankar, K. Kumar, R. K. Rawal, ‘Synthetic and Medicinal Prospective of Structurally Modified Curcumins’, Curr. Top. Med. Chem. 2017, 17, 148–161.
- 113M. Mittal, K. Kumar, D. Anghore, R. K. Rawal, ‘ICP-MS: Analytical Method for Identification and Detection of Elemental Impurities’, Curr. Drug Discovery Technol. 2017, 14, 106–120.
- 114P. Talwan, S. Choudhary, K. Kumar, R. K. Rawal, ‘Chemical and Medicinal Versatility of Substituted 1,4-Dihydropyridines’, Curr. Bioact. Compd. 2017, 13, 109–120.
- 115S. Pawar, M. K. Kumawat, M. Kundu, K. Kumar, ‘Synthetic and Medicinal Perspective of Aantileishmanial Agents: An Overview’, J. Mol. Struct. 2023, 1271, 133977.
