Benzimidazole-Triazole Hybrids as Antimicrobial and Antiviral Agents: A Systematic Review

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, -CF3, -NO2, -CN, -CHO, -OH, OCH3, COOCH3), 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.

Structure-based development of 3,5-dihydroxybenzoyl-hydrazineylidene as tyrosinase inhibitor; in vitro and in silico study

“…Different studies also confirmed the high potency of triazole and its analogs as anticancer 10 – 12 , anti-microbial 13 , 14 , anti-inflammatory 15 , 16 , and anti-melanogenic agents as tyrosinase inhibitors. In this category, triazole-benzoimidazole (Compound F) with IC 50 = 9.42 μM is a good example 17 .…”

Recent Advances in the Fixation of CO2 into Quinazoline and Benzimidazole

“…Benzimidazole is widely used in antihypertensive, antituberculous, anti-inflammatory, antibacterial, antiviral, analgesic, antihypertensive, antibacterial, and rare applications in cardiovascular diseases. ,− Vitamin B12 consists of benzimidazole, and also thiabendazole, azomycin, chlotrimazole, mebendazole, Omeprazole and albendazole, rabeprazole are the important drugs composed of benzimidazole derivatives. , The synthesis of benzimidazole and quinazoline is 100% atom efficient due to 100% utilization of CO 2 and other substrates . Traditionally, benzimidazole was synthesized from DMF (dimethylformamide) derivatives, formic acid, esters, and methanol. − Benzimidazole was synthesized using a basic medium or strong medium, toxic reagents and high temperatures, but nowadays the synthesis is more environmentally friendly and sustainable by using catalysts. , Another important intermediate used in the pharmaceutical industry is quinazolines-2,4­(1 H ,3 H )-diones synthesized by harmful chemicals such as anthranilamide with phosgene, anthranilic acid with urea, and antranilic acid with chlorosulfonyl isocyanate or potassium cyanate (Figure ).…”

Synthesis, In Vitro Biological Evaluation and Molecular Modeling of Benzimidazole-Based Pyrrole/Piperidine Hybrids Derivatives as Potential Anti-Alzheimer Agents

“…Benzimidazole possesses a diverse range of biological activities, such as anti-hypertensive [ 11 , 12 ], anti-Alzheimer’s [ 13 ], anti-microbial, anti-viral [ 14 ], anti-diabetic [ 15 , 16 ] and anti-cancer activities [ 17 ]. There are some drug molecules, such as benoxaprofen, albendazole, enviradine, bendamastine, omeprazole and astemizole, which contain a benzimidazole moiety in their skeleton ( Figure 2 ) [ 18 ].…”