Citation: Marinescu, M. Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review. Antibiotics 2023, 12, 1220. https://doi.org/ 10.3390/antibiotics12071220 Academic Editor: Helena Felgueiras Received: 30 June 2023 Revised: 14 July 2023 Accepted: 19 July 2023 Published: 22 July 2023 Copyright: © 2023 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). antibiotics Review Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review Maria Marinescu Department of Organic Chemistry, Biochemistry and Catalysis, Faculty of Chemistry, University of Bucharest, 030018 Bucharest, Romania; maria.marinescu@chimie.unibuc.ro Abstract: Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles, and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole- triazole hybrids with improved biological properties compared to the properties of simple mono- heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure–activity relationship reported in the literature. It was found that the presence of certain groups grafted onto the benzimidazole and/or triazole nuclei (-F, -Cl, -Br, -CF 3 , -NO 2 , -CN, -CHO, -OH, OCH 3 , COOCH 3 ), as well as the presence of some heterocycles (pyridine, pyrimidine, thiazole, indole, isoxazole, thiadiazole, coumarin) increases the antimicrobial activity of benzimidazole-triazole hybrids. Also, the presence of the oxygen or sulfur atom in the bridge connecting the benzimidazole and triazole rings generally increases the antimicrobial activity of the hybrids. The literature mentions only benzimidazole-1,2,3-triazole hybrids with antiviral properties. Both for antimicrobial and antiviral hybrids, the presence of an additional triazole ring increases their biological activity, which is in agreement with the three-dimensional binding mode of compounds. This review summarizes the advances of benzimidazole triazole derivatives as potential antimicrobial and antiviral agents covering articles published from 2000 to 2023. Keywords: benzimidazole; triazole; hybrids; antimicrobial; antiviral; pharmaceutical properties 1. Introduction Heterocyclic compounds have a central place in medicinal chemistry, being used as therapeutic agents to treat most diseases [1–3]. Among these heterocycles, benzimidazole stands out, as a purine-analog pharmacophore, with a very diverse therapeutic activity. The very broad spectrum of biological activities it treats include antimicrobial [4–8], antivi- ral [9,10], antihistamine [11,12], anticonvulsant [3,13], antitumor [14–16], proton pump in- hibitors [17], antiparasitic [16,18,19], anti-inflammatory [20–22], or antihypertensive [23,24] activities. Some benzimidazoles are efficient agents in Diabetes mellitus [25–27], while astemizole compounds possess anti-prion activity to treat Creutzfeldt-Jakob disease [5,28]. The literature also reports anti-Alzheimer [29,30], psychoactive, anxiolytic, analgesic [31,32], and anticoagulant properties [33,34] of benzimidazole derivatives. Additionally, triazole compounds possess a diversity of biological activities as an- timicrobial [35–38], antitubercular [39,40], potential inhibitors of SARS-CoV-2 [41–43], antiviral [43,44], anti-inflammatory [45,46],antitumor [47–50], antihypertensive [50], an- tioxidant [47,51,52], and antiepileptic [53,54]. Pharmacological applications of triazoles Antibiotics 2023, 12, 1220. https://doi.org/10.3390/antibiotics12071220 https://www.mdpi.com/journal/antibiotics