Novel 1,2,4-triazole derivatives as antitumor agents against hepatocellular carcinoma

Radwan, Rasha R.; Zaher, Nashwa H.; El‐Gazzar, Marwa G.

doi:10.1016/j.cbi.2017.07.008

Cited by 29 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, in one of our previous studies, the anticancer effects of triazolothiadiazines on epithelial cancers, especially liver cancer, were demonstrated, where compounds were able to induce apoptotic cell death due to oxidative stress, acting on Akt protein [13]. Furthermore recently the antiproliferative bioactivities of a compound with triazolothiadiazine scaffold against human hepatoma cell line (HepG2) was reported [27]. In light of this information and as a part of our ongoing interest on liver cancer therapeutics [28], we investigated the anticancer effects of our newly synthesized compounds bearing triazolethiones (1-8) or triazolothiadiazine (1a-8c) cores, which we reported as potent analgesic/anti-in ammatory compounds previously (Fig.…”

Section: Introductionmentioning

confidence: 97%

New Triazolothiadiazine Derivative Inhibits Stemness and Induces Cell Death in HCC by Oxidative Stress Dependent JNK Pathway Activation

Kahraman

Güven

Aytac

et al. 2021

Preprint

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer, and resistant to both conventional and targeted chemotherapy. (NSAIDs) Recently, nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease the incidence and mortality of different types of cancers. Here, we investigated the cellular bioactivities of a series of triazolothiadiazine derivatives on HCC, which have been previously reported as potent analgesic/anti-inflammatory compounds. From the initially tested 32 triazolothiadiazine NSAID derivatives, 3 compounds were selected based on their IC50 values for further molecular assays on 9 different HCC cell lines. 7b, which was the most potent compound, induced G2/M phase cell cycle arrest and apoptosis in HCC cells. Cell death was due to oxidative stress-induced JNK protein activation, which involved the dynamic involvement of ASK1, MKK7, and c-Jun proteins. Moreover, 7b treated nude mice had a significantly decreased tumor volume and prolonged disease-free survival. 7b also inhibited the migration of HCC cells and enrichment of liver cancer stem cells (LCSCs) alone or in combination with sorafenib. With its ability to act on both proliferation, stemness and the migration of HCC cells, 7b can be considered for the therapeutics of HCC, which has an increased rate of incidence ~3% annually.

show abstract

Section: Introductionmentioning

confidence: 97%

New Triazolothiadiazine Derivative Inhibits Stemness and Induces Cell Death in HCC by Oxidative Stress Dependent JNK Pathway Activation

Kahraman

Güven

Aytac

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…On account of its high activity, low toxicity, perfect selectivity, and variable biological properties, nitrogen‐containing heterocyclic compounds are one of the most important classes of applied branches of organic chemistry. [ 8 ] 1,2,4‐Triazoles, a member of this class, have attracted great attention over the past few decades due to their important pharmacological properties such as antifungal, [ 9 ] antibacterial, [ 10 ] analgesic, [ 11 ] antitumor, [ 12 ] antiviral, [ 13 ] antioxidant, [ 14 ] antihypertensive, [ 15 ] anti‐inflammatory, [ 16 ] pesticidal, [ 17 ] herbicidal, [ 18 ] and insecticidal. [ 19 ] In addition to these properties, many recent studies have reported that various 1,2,4‐triazole analogs can be used as potential enzyme inhibitors such as urease, [ 20 ] lipase, [ 21,22 ] α‐glucosidase, [ 22,23 ] α‐amylase, [ 23 ] carbonic anhydrase (II), [ 24,25 ] acetylcholinesterase, butyrylcholinesterase, [ 25,26 ] tyrosinase, [ 27 ] kinase, [ 28,29 ] DNA gyrase, [ 30 ] and monoamine oxidase (MAO‐A and MAO‐B).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new 1,2,4‐triazole–(thio)semicarbazide hybrid molecules: Their tyrosinase inhibitor activities and molecular docking analysis

Gültekin

Bekircan

Kolcuoğlu

et al. 2021

Archiv der Pharmazie

View full text Add to dashboard Cite

Tyrosinase inhibition is very important in controlling melanin synthesis. If melanin synthesis is not controlled in metabolism, an unwanted increase in melanin synthesis occurs. As melanin plays a role in the formation of skin color, its unusual levels cause some skin disorders such as pregnancy scars, age spots, and especially skin cancer (melanoma). However, the tyrosinase activity is also related to Parkinson's disease and some neurodegenerative diseases. For all these reasons, the medicinal as well as the cosmetic industries focus on research on tyrosinase inhibitors for the treatment of skin disorders and some neurodegenerative diseases. In this study, 32 new 1,2,4‐triazole–(thio)semicarbazide hybrid molecules (6a–p and 7a–p) were synthesized, starting from 4‐amino‐1‐pentyl‐3‐phenyl‐1H‐1,2,4‐triazole‐5(4H)‐one. These compounds were evaluated for their inhibitory activity against mushroom tyrosinase. The results indicated that 6h, 6m, 6n, and 6p exhibited the most effective inhibitory activity, with IC50 values of 0.00162 ± 0.0109, 0.00166 ± 0.0217, 0.00165 ± 0.019, and 0.00197 ± 0.0063 μM, respectively, compared with kojic acid as the reference drug (IC50 = 14.09 ± 0.02 μM). Also, molecular docking analyses were performed to suggest possible binding poses for the ligands. As a result, derivatives 6h, 6m, 6n, and 6p can be used as promising tyrosinase inhibitor candidates in the medicinal, cosmetics, or food industries.

show abstract

“…The development of triazole chemistry (especially, 1,2,3‐triazoles and 1,2,4‐triazoles) has attracted attention of researchers, because of the wide range of properties of triazoles. Primarily, it is the antitumor activity of triazole derivatives (El‐Sherief et al, ; Liu et al, ; Mohamed et al, ; Radwan et al, ) toward different cell lines (human promyelocytic leukemia cells, human colon carcinoma cells, human prostate cells, etc. ), which is expressed in a very low half minimal inhibitory concentration IC 50 values (≈2 nM) in some cases.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Systems Based on Novel Amphiphiles and a Polymer: Aggregation and Selective Solubilization

Gabdrakhmanov

Samarkina

Krylova

et al. 2019

J Surfact & Detergents

View full text Add to dashboard Cite

Supramolecular systems based on novel triazole‐containing and pyrimidine‐containing amphiphiles bearing OH‐groups and a hydrophilic polymer (polyethyleneimine, PEI) were fabricated. Aggregation threshold of individual amphiphile solutions and a surfactant/polymer binary mixture were determined to be equal to 2 and 0.05 mM, respectively, using tensiometry and conductometry techniques. It was found, that PEI addition to surfactant aqueous solutions induces the transition from open to closed association mode accompanying the decrease of mean hydrodynamic diameter of particles (D H) from 100 nm to D H ≤ 5 nm. Polymer addition to the system results in the leveling of pH decrease with surfactant concentration and increase of the electrokinetic potential values from 10 mV up to 40 mV. It was established that solubilization capacity of the supramolecular system formed could be increased by transition from surfactant individual solutions to the amphiphile/polymer binary system. The solubilization properties of the system strongly depend on the nature of the hydrophobic guest solubilized and differ by two orders of magnitude for hydrophobic azodye and lipophilic oxime.

show abstract

Novel 1,2,4-triazole derivatives as antitumor agents against hepatocellular carcinoma

Cited by 29 publications

References 35 publications

New Triazolothiadiazine Derivative Inhibits Stemness and Induces Cell Death in HCC by Oxidative Stress Dependent JNK Pathway Activation

New Triazolothiadiazine Derivative Inhibits Stemness and Induces Cell Death in HCC by Oxidative Stress Dependent JNK Pathway Activation

Synthesis of new 1,2,4‐triazole–(thio)semicarbazide hybrid molecules: Their tyrosinase inhibitor activities and molecular docking analysis

Supramolecular Systems Based on Novel Amphiphiles and a Polymer: Aggregation and Selective Solubilization

Contact Info

Product

Resources

About