In vitro and histological investigation of antitumor effect of some triazole compounds in colon cancer cell line

Abstract

1,2,4-Triazoles are used as antifungal, antibacterial, antimicrobial, and antioxidant against some oxidative radical species. Recently, many 1,2,4triazoles continue to be synthesized. In this study, the effect of the 1,2,4-triazole derivatives on human colon cancer (HT29) was investigated in vitro and in vivo in rats. MTT test was applied to in in vitro experiments. For in vivo study, rats were divided into seven groups as follows: Control group (negative control), azoxymethane (AOM), AOM + cisplatin 15, AOM + L1, AOM + L2, AOM + L3, and AOM + L4. To create colon cancer, the AOM injection was injected subcutaneously at a dose of 15 mg/kg, three times (once weekly). The in vivo studies were completed at 28 weeks. It was found that the 1,2,4-triazole derivatives reduced the cell viability (P < 0.05). In all animals in the experimental groups, mild dysplasia was detected in 100% of the colon mucosal epithelium. Severe dysplasia and adenocarcinoma were observed in L1 groups. As a result, this study determined that the 1,2,4-triazole derivatives exhibit antitumor activity. K E Y W O R D Sazoxymethane, colon cancer, HT29, 1,2,4-triazole | INTRODUCTIONIn the United States, colorectal cancer (CRC) is the second leading cause of cancer-related deaths. 1 In United States, 135 430 people were diagnosed with CRC and about 50 260 died from CRC in 2017. 2 CRC is the third most commonly diagnosed cancer and the third leading cause of cancer-specific mortality in both men and women. As of 2017, 95 520 new colon cancer cases (colon cancer alone) and 50 260 deaths (colon and rectum cancers in combination) are estimated to occur in the United States. With the increase in the access to and use

In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones—Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles

“…Recently, research on nitrogen‐containing heterocyclic compounds has increased due to their significant biological activities. Detailed studies have been conducted on the activities of triazole compounds due to their biological properties . Five‐membered cyclic compounds that contain three nitrogen atoms are known as triazoles or as "triazacyclopentadienes."…”

“…Therefore, it is necessary to design and synthesize novel triazole derivatives with broad‐spectrum and lower toxicity for antifungal applications. Still, new triazole derivatives with different substituents are being researched and added to the literature …”

Anticancer Activity of Mannich Bases: A Review of Recent Literature

“…Synthesis and anticancer properties of bis‐Mannich bases derived from substrates in which two identical 1,2,4‐triazole scaffolds are connected through an alkyl linker have been disclosed in two recent articles. One of these studies determined that approximately 70 to 80 % of the MCF‐7 cancer cells remained viable after treatment with Mannich bases 157 (Figure 18) at a concentration of 10 μM, [153] while the other study showed that Mannich bases 158 (Figure 18) were generally as potent as cisplatin (14 % cell viability) against HT‐29 colon cancer cells, but they increased precursor lesions and accelerated tumor onset in vivo [154] …”

“…One of these studies determined that approximately 70 to 80 % of the MCF-7 cancer cells remained viable after treatment with Mannich bases 157 (Figure 18) at a concentration of 10 μM, [153] while the other study showed that Mannich bases 158 (Figure 18) were generally as potent as cisplatin (14 % cell viability) against HT-29 colon cancer cells, but they increased precursor lesions and accelerated tumor onset in vivo. [154] Oxadiazolethiones are N-aminomethylated in a manner similar to triazolethiones, and several examples of Mannich ChemMedChem bases of oxadiazolethiones with anticancer properties can be found in recent literature. One Mannich base 145 (X = O) (Figure 18) in a series of six compounds was found to be more potent than 5-fluorouracil against LnCaP and PC-3 prostate cancer cell lines, but it had no activity against DU145 cell line.…”