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

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          Abstract

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

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          Most cited references70

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          A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes.

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            Antifungal agents: mechanisms of action

            Clinical needs for novel antifungal agents have altered steadily with the rise and fall of AIDS-related mycoses, and the change in spectrum of fatal disseminated fungal infections that has accompanied changes in therapeutic immunosuppressive therapies. The search for new molecular targets for antifungals has generated considerable research using modern genomic approaches, so far without generating new agents for clinical use. Meanwhile, six new antifungal agents have just reached, or are approaching, the clinic. Three are new triazoles, with extremely broad antifungal spectra, and three are echinocandins, which inhibit synthesis of fungal cell wall polysaccharides--a new mode of action. In addition, the sordarins represent a novel class of agents that inhibit fungal protein synthesis. This review describes the targets and mechanisms of action of all classes of antifungal agents in clinical use or with clinical potential.
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              Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides.

              The cycloaddition of azides to alkynes is one of the most important synthetic routes to 1H-[1,2,3]-triazoles. Here a novel regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes to azides on solid-phase is reported. Primary, secondary, and tertiary alkyl azides, aryl azides, and an azido sugar were used successfully in the copper(I)-catalyzed cycloaddition producing diversely 1,4-substituted [1,2,3]-triazoles in peptide backbones or side chains. The reaction conditions were fully compatible with solid-phase peptide synthesis on polar supports. The copper(I) catalysis is mild and efficient (>95% conversion and purity in most cases) and furthermore, the X-ray structure of 2-azido-2-methylpropanoic acid has been solved, to yield structural information on the 1,3-dipoles entering the reaction. Novel Fmoc-protected amino azides derived from Fmoc-amino alcohols were prepared by the Mitsunobu reaction.
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                Author and article information

                Contributors
                Journal
                Front Mol Biosci
                Front Mol Biosci
                Front. Mol. Biosci.
                Frontiers in Molecular Biosciences
                Frontiers Media S.A.
                2296-889X
                25 April 2022
                2022
                25 April 2022
                : 9
                : 864286
                Affiliations
                [1] 1 Bioorganic and Medicinal Chemistry Laboratory , Faculty of Science , Department of Chemistry , University of Chittagong , Hathajari , Chittagong, Bangladesh
                [2] 2 Department of Chemical Engineering and Energy Sustainability , Faculty of Engineering , Universiti Malaysia Sarawak , Kuching, Malaysia
                [3] 3 Department of Pharmaceutical Chemistry , Faculty of Pharmacy , Umm Al-Qura University , Makkah, Saudi Arabia
                [4] 4 Genetic Engineering and Biotechnology , University of Rajshahi , Rajshahi, Bangladesh
                [5] 5 Department of Pharmacy Practice , College of Pharmacy , AlMaarefa University , Ad Diriyah, Saudi Arabia
                [6] 6 Department of Pharmaceutics , College of Pharmacy , King Saud University , Riyadh, Saudi Arabia
                Author notes

                Edited by: Mohammad Arshad, Shaqra University, Saudi Arabia

                Reviewed by: Zhe-shan Quan, Yanbian University, China

                Afzal Basha Shaik, Jawaharlal Nehru Technological University, India

                *Correspondence: Mohammed M. Matin , mahbubchem@ 123456cu.ac.bd

                This article was submitted to Molecular Diagnostics and Therapeutics, a section of the journal Frontiers in Molecular Biosciences

                Article
                864286
                10.3389/fmolb.2022.864286
                9081720
                35547394
                9482e877-63a5-48e7-829d-f81f80bac755
                Copyright © 2022 Matin, Matin, Rahman, Ben Hadda, Almalki, Mahmud, Ghoneim, Alruwaily and Alshehri.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 January 2022
                : 08 March 2022
                Categories
                Molecular Biosciences
                Mini Review

                anticancer agents,azide–alkyne cycloaddition,cefatrizine,isomeric triazoles,microwave-assisted green synthesis,pharmacological applications,sars-cov-2,triazole–thiazole hybrids

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