The therapeutic efficacy of 1,2,3-triazoles in cancer

 Corresponding author: Rasha Ahmed Hashim Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0. The therapeutic efficacy of 1,2,3-triazoles in cancer K.M. Tawfiq, Mayada Sabri and Rasha Ahmed Hashim * Chemistry Department, College of Education for Pure Science/Ibn Al-Haitham, University of Baghda. GSC Biological and Pharmaceutical Sciences, 2025, 32(03), 103–107 Publication history: Received on 30 July 2025; revised on 05 September 2025; accepted on 07 September 2025 Article DOI: https://doi.org/10.30574/gscbps.2025.32.3.0351 Abstract The financial and human toll of cancer's global impact cannot be quantified. Unfortunately, the side effects of cancer treatments are often severe. Drug resistance is another issue doctors must address when treating cancer. Other factors that contribute to an increased risk of cancer include alcohol consumption, poor nutrition, water and air pollution, and tobacco use. Derivatives of 1,2,3 triazole and their groups have gained a lot of importance due to their diverse biological activities and their ability to treat cancer. This is evident in the toxic effect of transition metal compounds and heterocyclic compounds in the formation of stable communities, which increases their effect on diverse groups of cancer cells through the direct pharmacological effect on the target cells. This is due to the unique structure of the triazole ring, which allows hydrogen bonds and stacking of π–π in coordination with the metal center. The acyclic part contains nitrogen 1-2-3-triazoles, five groups that perform various therapeutic functions. There are many drugs approved for the treatment of a wide range of cancers that contain 1-2-3-triazoles, in addition to pharmaceutical compounds that are in the clinical research stage. Therefore, the importance of the compound is increasing in the field of cancer research. Keywords: Cancer; 1,2,3 Triazole; Global impact; Side effects; Treatments 1. Introduction Cancer is one of the main causes of death. It is likely that the number of people with cancer will reach 29.5 million in 2040. This highlights the need to develop more appropriate and effective cancer drugs that overcome the obstacles resulting from side effects.)1) This makes it a duty for researchers to produce effective drugs against cancer. Heterocyclic compounds, triazoles, have clearly shown promise in the future due to their distinctive biological properties and ease of synthesis. Among them, 12-3-triazoles have received great attention if the development of cancer drugs becomes possible. (2) In addition to being a drug carrier, the 1-2-3 triazole structure has the ability to react and add an alkane-aide ring, carrying both drugs One of the mechanistic properties of the compound is that it inhibits the growth of cancer cells. Many hybrid compounds containing 1-2-3-triazole have been produced and synthesized due to their anticancer properties in vitro and in vivo. Inorganic compounds contain biologically active heteroatoms, such as nitrogen, sulfur oxygen, and others, which are toxic to target cells. (3) GSC Biological and Pharmaceutical Sciences, 2025, 32(03), 103–107 104 The nitrogen ring is a heterocyclic molecule containing five parts called azoles. It represents a promising future. This is due to the presence of two heterogeneous nitrogen atoms, which play a significant role in changing the structure and biological reactions.This review includes the role of the compound in combating various types of cancer. (4) 2. Chemistry: synthesis and properties of the 1,2,3-triazoles 1-2-3-Triazole is prepared by the reaction of azide with alkynes. The preparation is facilitated by techniques called RuAAC or CuAAC by using Click Chemistry The chemical and physical properties of the compound are characterized by high stability against hydrolysis or oxidation thanks to the double bonds present in the ring. The hydrogen atoms are the reason for the polarity of triazole and its solubility in water. The electronic nature allows it to be easily bound to proteins or enzymes through hydrogen bonds. (5) Image (1) shows three different forms of the 1,2,3-triazole compound. The 1,2,3-triazole types (tautomers) differ in the location of the hydrogen atom bonded to the nitrogen atoms in the five-membered ring. • In this form (1), the hydrogen atom is bonded to nitrogen atom number 1H-1,2,3-Triazole • In this form (2), the hydrogen atom is bonded to nitrogen atom number 2 (N2), • which changes the electron distribution in the ring and affects the chemical properties of the compound.4H1,2,3-TriazoleIn this form, the hydrogen atom is bonded to carbon atom number 4 (C4) • rather than to any of the nitrogen atoms. This form is less common • and may be less stable than the other forms. (6) Figure 1 The formulas in which 1-2-3-triazoles exit 2.1.1. triazoles anti-cancer study shows that 4-1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)-methoxy, a new derivative of 1,2,3-triazole, was produced. The compound 2-hydroxybenzaldehyde was produced by CuAAC, which stands for copper(I)-catalyzed azide-alkyne cycloaddition. Fourier transform infrared spectroscopy (FTIR), 1H NMR, 13C NMR, and UV-vis spectroscopy were performed to study the structure of the compound. The molecule was adapted to a monoclinic crystal system with space group P21/c, according to X-ray crystallography experiments. (7). The study showed that hydrogen bonds and van der Waals interactions are the main interactions that developed in the crystal packing. The unit cell volume of the crystal space was determined to be 152.10 Å3, and the proportion of free space in it was 9.80%.Through energy analysis, it was found that dispersion energy dominated the stability of the complex (8)The study on the binding activity of the complex to DNA/bovine serum albumin (BSA) showed that interference was mediated in the binding activity of the complex to CT DNA and that BSA binding activity was mediatedThe 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay was also used to study the anticancer activity of the compound using human cell lines such as MDA-MB-231, LNCaP, Caco-2, and HEK-293. On Caco-2 cancer cells, the compound showed greater cytotoxicity than cisplatin and etoposide, with an IC50 value of After 48 hours, a value of 16.63 ± 0.27 μM was observed. Annexin V recommends the use of apoptosis to increase cell death. The study showed that reactive oxygen species (ROS) may lead to programmed cell death through the production of ROS. (9) Chemotherapy is a primary method of combating breast cancer, but multidrug resistance and severe side effects epresent major obstacles to successful treatment, highlighting the need to develop new drugs. Hence, we find the role of 1-2-3-triazoles, which can be synthesized by (Click Chemistry) and can function efficiently as a linking group between different drug molecules and as an active drug component in its own right due to the formation of hydrogen bonds, their moderate dipole moment, and their water solubility. This demonstrates the effectiveness of triazoles against various forms of breast cancer and their ability to selectively target multiple biological pathways. (10) GSC Biological and Pharmaceutical Sciences, 2025, 32(03), 103–107 105 For lung cancer, which is the most common type and causes about a quarter of cancer deaths worldwide, 1-2-3-triazole compounds have shown promising therapeutic potential due to their ability to bind to enzymes and receptors and target important biological pathways, paving the way for the development of anti-lung cancer drugs. (11) Research indicated biological activity through the effect of anticancer molecules. Novel compounds were selected to screen cancer cell lines in the laboratory. Initially, approximately 60 cell lines were selected at a concentration of 10-5, using a single dose of the primary anticancer assay. (12) These cells represented different types of cancer, represented by human cancer cell lines. Each cell line was injected and pre-incubated on a microtiter plate for 24 to 48 hours as part of the screening protocol. After adding test chemicals at a single concentration, the culture was incubated for an additional 48 hours. Sulforhodamine B (SRB), a protein-binding dye, was used to determine endpoints. The percentage growth of treated cells compared to untreated control cells was used to determine the results for each test agent. (13) The growth rate (GP) was used to infer the results of each compound. The growth range shows the minimum and maximum growth rates observed in various cancer cell lines for the evaluated lines. (14) The 1-2-3-triazole compounds showed low to minimal activity. However, some chemicals were found to have a selective effect on a number of cancer cell lines.Most of the drugs studied have shown inhibition of leukemia and breast cancer cell lines, in addition to kidney cancer cells. (15) The study demonstrated that 1-2-3-triazole derivatives have effective potential to inhibit acute myeloid leukemia cells. 1-2-benzisoxazole demonstrated strong antiproliferative activity in the MTT assay against MV4-11 cells, with an IC50 of 2 μM.As a compound developer using click chemistry, its antiproliferative potential against cancer cells was tested. (16) The compound was successful and demonstrated inhibitory activity against MCF-7 (breast cancer) cells with an IC50 value of 46 µM. However, the biotulin compound, which demonstrated a 30% inhibitory effect on MCF-7 cells and a 90% inhibitory effect on HCT-116 cells after 48 hours of incubation, was found to be more toxic to the cells. (17) For 1,2,3-triazole compounds, derived from sugars, since carbohydrates can alter drug behavior, these compounds appear to be useful complementary therapies for cancer drugs. They are important in terms of drug kinetics, cellular uptake, target specificity, and bioavailability (18). Studies have shown that carbohydrate-based 1,2,3-triazole drugs exhibit better properties, including greater stability and high-water solubility, which reduces the problems of poor water solubility and reduced chemical stability (19). Triazole compounds conjugated with carbohydrates protect against rapid clearance from the reticuloendothelial system (RES), increasing systemic exposure and enhancing therapeutic efficacy. Carbohydrates enhance receptormediated phagocytosis, enabling anticancer drugs to enter cells and bypass biological barriers that prevent them from entering tumor tissue Click-triggered hybrid derivatives of ipodophyllotoxin and galactose from 1,2,3-triazoles were used to produce. Compared to cisplatin (16) (IC50 = 9.24 μM, MTT assay) and etoposide (17) (IC50 = 11.92 μM, MTT assay), these compounds demonstrated a potent antiproliferative effect against A549 cells (IC50 = 4.07 μM, MTT assay), a double effect. The 1,2,3-triazole ring is an important pharmacophore system in nitrogen-containing heterocyclic compounds. These five-membered heterocyclic forms with three heteroatoms are feasible for synthesis using click chemistry and copperor ruthenium-catalyzed azide-alkyne cycloaddition. (18). New hybrid and conjugated compounds containing 1,2,3triazoles have been produced, becoming important substrates for various biological behaviors after 1,2,3-triazole compounds were shown to have a "linking" property (19). Their anticancer, antidiabetic, antiviral, antibacterial, antituberculosis, antileishmanial, neuroprotective, and antimalarial properties have been demonstrated. 1,2,3-Triazole metal complexes also exhibit anticancer activity (20). Copper (II) complexes containing triazole ligands, with IC values in the low micromolar range, demonstrated a marked effect against breast and colon cancer cells. Ruthenium-triazole complexes were found to have low toxicity to normal tissues and were capable of targeting malignant cells. (20) Several triazole-based compounds with antiproliferative properties have been developed to demonstrate their efficacy both in vitro and in vivo. Taking into account their molecular structure, their designed mechanisms of action, and the types of cancer cells targeted, these compounds exhibit significant differences. (21) GSC Biological and Pharmaceutical Sciences, 2025, 32(03), 103–107 106 3. Conclusion Triazole metal complexes are inorganic biomolecules with a promising future in cancer therapy. Since Anticancer compounds derived from triazoles have been widely developed. They vary greatly in their composition and mode of action. Their synthesis methods, efficacy, and targetability have proven promising in the future for the development of broad-spectrum drugs to safely combat all types of cancer. 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