Triazoles and Their Derivatives: Chemistry, Synthesis, and Therapeutic Applications

Frontiers in Molecular Biosciences, Год журнала: 2022, Номер 9

Опубликована: Апрель 25, 2022

Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered triazoles: 1,2,3-triazole and 1,2,4-triazole. Due to structural characteristics, both 1,2,3- 1,2,4-triazoles able accommodate a broad range substituents (electrophiles nucleophiles) around core structures pave way for construction diverse novel bioactive molecules. Both their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, antidepressant activities. These also important in organocatalysis, agrochemicals, materials science. Thus, they therapeutic applications ever-widening future scope across scientific disciplines. However, adverse events such as hepatotoxicity hormonal problems lead careful revision azole family obtain higher efficacy minimum side effects. This review focuses on features, synthesis, notable related compounds.

Язык: Английский

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1,2,3-Triazole-Benzofused Molecular Conjugates as Potential Antiviral Agents against SARS-CoV-2 Virus Variants

Life, Год журнала: 2022, Номер 12(9), С. 1341 - 1341

Опубликована: Авг. 29, 2022

SARS-CoV-2 and its variants, especially the Omicron variant, remain a great threat to human health. The need discover potent compounds that may control virus pandemic emerged mutants is rising. A set of 1,2,3-triazole and/or 1,2,4-triazole was synthesized either from benzimidazole or isatin precursors. Molecular docking studies in vitro enzyme activity revealed most investigated demonstrated promising binding scores against spike proteins, comparison reference drugs. In particular, compound 9 has highest scoring affinity proteins with IC50 reaching 75.98 nM protein 74.51 protein. possible interaction between triazoles viral by prevention entry into host cells, which led reduction reproduction infection. cytopathic inhibition assay airway epithelial cell line (Vero E6) infected effectiveness safety (compound 9) (EC50 CC50 reached 80.4 1028.28 µg/mL, respectively, selectivity index 12.78). Moreover, antiinflammatory effect tested pave way reduce reported SARS-CoV-2-induced hyperinflammation.

Язык: Английский

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Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential

Pharmaceuticals, Год журнала: 2023, Номер 16(3), С. 463 - 463

Опубликована: Март 20, 2023

COVID-19 infection is now considered one of the leading causes human death. As an attempt towards discovery novel medications for pandemic, nineteen compounds containing 1,2,3-triazole side chains linked to phenylpyrazolone scaffold and terminal lipophilic aryl parts with prominent substituent functionalities were designed synthesized via a click reaction based on our previous work. The assessed using in vitro effect growth SARS-CoV-2 virus-infested Vero cells different compound concentrations: 1 10 μM. data revealed that most these derivatives showed potent cellular anti-COVID-19 activity inhibited viral replication by more than 50% no or weak cytotoxic harboring cells. In addition, assay employing SARS-CoV-2-Main protease inhibition was done test inhibitors' ability block common primary virus as mode action. obtained results show non-linker analog 6h two amide-based linkers 6i 6q active IC50 values 5.08, 3.16, 7.55 μM, respectively, against comparison selective antiviral agent GC-376. Molecular modeling studies placement within binding pocket which reveal conserved residues hydrogen bonding non-hydrogen interactions fragments: triazole scaffold, part, linker. Moreover, stability their target also studied analyzed molecular dynamic simulations. physicochemical toxicity profiles predicted, behave low organ toxicity. All research point potential usage new chemotype promising leads be explored vivo might open door rational drug development Main medicines.

Язык: Английский

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Benchmarking the ability of novel compounds to inhibit SARS-CoV-2 main protease using steered molecular dynamics simulations

Computers in Biology and Medicine, Год журнала: 2022, Номер 146, С. 105572 - 105572

Опубликована: Апрель 29, 2022

Язык: Английский

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Antimicrobial and in-silico evaluation of novel chalcone and amide-linked 1,4-disubstituted 1,2,3 triazoles

Journal of Molecular Structure, Год журнала: 2022, Номер 1257, С. 132632 - 132632

Опубликована: Фев. 13, 2022

Язык: Английский

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Novel 1,2,3‐Triazole Derivatives as Potential Inhibitors against Covid‐19 Main Protease: Synthesis, Characterization, Molecular Docking and DFT Studies

ChemistrySelect, Год журнала: 2021, Номер 6(14), С. 3468 - 3486

Опубликована: Апрель 14, 2021

The highly contagious nature of Covid-19 attracted us to this challenging area research, mainly because the disease is spreading very fast and until now, no effective method a safe treatment or vaccine developed. A library novel 1,2,3-triazoles based 1,2,4-triazole, 1,3,4-oxadiazole and/or 1,3,4-thiadiazole scaffolds were designed successfully synthesized. Different spectroscopic tools efficiently characterized all newly synthesized hybrid molecules. An interesting finding that some compounds revealed two isomeric forms. ratio affected by size attached group as well type heteroatom forming side ring central 1,2,3-triazole ring. experimental data in agreement with DFT calculations at B3LYP 6-31G (d,p) regard geometrical conformation prepared compounds. results stability one form over other range 0.057-0.161 Kcal mol-1. docking study was performed using PyRx AutoDockVina investigate activity antiviral agents. Bond affinity scores derivatives detected -6.0 -8.8 kcal/mol showing binding active sites 6LU7 protease hence could be anticipated inhibit enzyme. Verification Mpro alignment coronaviruses substrate-binding pockets COVID-19 against ligands. As per these results, it can proposed title molecules are acceptable candidates for possible medicinal

Язык: Английский

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A Comprehensive Update of Anti-COVID-19 Activity of Heterocyclic Compounds

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 1547 - 1571

Опубликована: Май 1, 2024

Abstract: The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) major causative agent COVID-19. severe symptoms this deadly include shortness breath, fever, cough, loss smell, and a broad spectrum other issues such as diarrhea, pneumonia, bronchitis, septic shock, multiple organ failure. Currently, there are no medications available for patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires development effective drugs specific treatments. Heterocycles important constituents more than 85% physiologically active pharmaceutical on market now. Several FDA-approved have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, hydroxychloroquine cure In study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that synthesized over past few years. These included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, benzodioxole. Both in vitro silico studies were performed to determine potential these fight against various proteins. Keywords: COVID-19, SARS-CoV-2, nucleus, vitro, silico, molecular docking

Язык: Английский

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Discovery of new benzothiazole-1,2,3-triazole hybrid-based hydrazone/thiosemicarbazone derivatives as potent EGFR inhibitors with cytotoxicity against cancer

RSC Advances, Год журнала: 2025, Номер 15(5), С. 3570 - 3591

Опубликована: Янв. 1, 2025

New benzothiazole-1,2,3-triazole hybrids-based hydrazone/thiosemicarbazone derivatives exhibited potent EGFR inhibitors with cytotoxicity against breast cancer.

Язык: Английский

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Halting Tumor Progression via Novel Non-Hydroxamate Triazole-Based Mannich Bases MMP-2/9 Inhibitors; Design, Microwave-Assisted Synthesis, and Biological Evaluation

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(19), С. 10324 - 10324

Опубликована: Сен. 25, 2021

Matrix metalloproteinases (MMPs) are key signaling modulators in the tumor microenvironment. Among MMPs, MMP-2 and MMP-9 receiving renewed interest as validated druggable targets for halting different progression events. Over last decades, a diverse range of MMP-2/9 inhibitors has been identified starting from early hydroxamic acid-based peptidomimetics to next generation non-hydroxamates. Herein, focused 1,2,4-triazole-1,2,3-triazole molecular hybrids with varying lengths decorations, mimicking thematic features non-hydroxamate inhibitors, were designed synthesized using efficient protocols alkylated pharmacophoric amines develop new Mannich bases. After full spectroscopic characterization newly triazoles tethering bases subjected safety assessment via MTT assay against normal human fibroblasts, then evaluated their potential anticancer activities colon (Caco-2) breast (MDA-MB 231) cancers. The relatively lengthy bis-Mannich 15 16 safer more potent than 5-fluorouracil sub-micromolar IC50 promising selectivity screened cancer cell lines rather cells. Both compounds upregulated p53 (2-5.6-fold) suppressed cyclin D expression (0.8-0.2-fold) studied cancers, thus, induced apoptosis. was superior terms cytotoxic activities, induction, suppression. Mechanistically, both comparable potencies reference prototype hydroxamate-based MMP inhibitor NNGH at concentrations. (IC50 = 0.143 µM) 4-fold (3.27-fold) over MMP-2, whereas NNGH. Concerning 0.376 1.2-fold active 15. Docking simulations predicted possible binding modes highlighted structural determinants inhibitory activities. Computational prediction physicochemical properties, ADMET, drug-likeness metrics revealed acceptable drug-like criteria.

Язык: Английский

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Synthesis, Characterization and Nanoformulation of Novel Sulfonamide-1,2,3-triazole Molecular Conjugates as Potent Antiparasitic Agents

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(8), С. 4241 - 4241

Опубликована: Апрель 11, 2022

Toxoplasma gondii (T. gondii) is a highly prevalent parasite that has no gold standard treatment due to the poor action or numerous side effects. Focused sulfonamide-1,2,3-triazole hybrids 3a-c were wisely designed and synthesized via copper catalyzed 1,3-dipolar cycloaddition approach between prop-2-yn-1-alcohol 1 sulfa drug azides 2a-c. The newly click products fully characterized using different spectroscopic experiments loaded onto chitosan nanoparticles form novel nanoformulations for further anti-Toxoplasma investigation. current study proved effectiveness of all examined compounds in experimentally infected mice. Relative sulfadiazine, (3c) nanoformulae demonstrated most promising result toxoplasmosis as it resulted 100% survival, reduction along with remarkable histopathological improvement studied organs.

Язык: Английский

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