1,2,4‐Triazole hybrids with potential antibacterial activity against methicillin‐resistant Staphylococcus aureus

Abstract

Methicillin‐resistant Staphylococcus aureus (MRSA) has developed numerous mechanisms of virulence and strategies to evade the human immune system, and it can be transmitted between humans, animals, and the environment. Thus, MRSA is an important cause of morbidity and mortality in both hospitals and in the community, creating an urgent demand for the development of novel anti‐MRSA candidates. The 1,2,4‐triazole nucleus is a bioisostere of amide, ester, and carboxylic acid, and the 1,2,4‐triazole ring is found in many compounds with diverse biological effects. 1,2,4‐Triazole derivatives could exert their antibacterial activity through inhibition of efflux pumps, filamentous temperature‐sensitive protein Z, penicillin‐binding protein, DNA gyrase, and topoisomerase IV, and they play an important role in the discovery of novel antibacterial agents. Among them, 1,2,4‐triazole hybrids, which have the potential to exert dual/multiple mechanisms of action, possess a promising broad‐spectrum antibacterial activity against a panel of clinically important drug‐resistant pathogens including MRSA. This review outlines the recent developments of 1,2,4‐triazole hybrids with a potential anti‐MRSA activity, covering articles published between 2010 and 2020. The mechanisms of action, critical aspects of their design, and structure–activity relationships are also discussed.

Synthesis of Antimicrobial Benzo[1,2,4]triazoloazepinium Salts and Tetrahydronaphtho[1,2-e][1,2,4]triazines by Polar [3+ + 2] and [4 + 2]-Cycloaddition Reactions

“…Numerous heterocycles containing [1,2,4]-triazole units have previously demonstrated promising antibacterial activity through inhibition of bacterial DNA gyrase, − which is a key enzyme involved in bacterial replication. Consequently, we reasoned that our triazolobenzoazepinium salts 5 might also be exhibiting their antibacterial activity in a similar manner and so decided to carry out in silico screening studies to determine their ability to inhibit DNA gyrase.…”

Evaluation of the antifungal and antibacterial action of a new unsaturated 1,2,4-triazole derivative (Nitrotriazon)

“…Lucrarea a fost realizată în cadrul proiectelor "Cercetări complexe de elaborare a noilor produse farmaceutice antiinfecțioase autohtone pentru optimizarea farmacoterapiei afecțiunilor stomatologice, orofaringiene și auriculare" cifru 20.80009.8007. 14…”

“…Este demonstrat faptul, că derivații de 1,2,4-triazol posedă activități anti-bacteriene promițătoare atât împotriva bacteriilor sensibile la medicamente, cât și a celor rezistente la medicamente [13]. Derivații de 1,2,4-triazol au capacitatea de a exercita activitatea lor antibacteriană prin inhibarea pompelor de eflux, a AND-girazei și topoizomerazei IV și joacă un rol important în descoperirea de noi agenți antibacterieni [14].…”

Synthetic and Medicinal Perspective of 1,2,4‐Triazole as Anticancer Agents

“…Literature data concluded that, fused heteroaromatic system exhibited excellent biological activity like N-alkyl-6-nitro-3,5-dihydro [1,2,4]triazolo [1,5-a]pyrimidin-7-amine, [1,2,4]triazolo [1,5-c]pyrimidines exhibited anticonvulsant and antiparasitic activity, respectively, as shown in Figure 1. [1] Among the heterocyclic systems, 1,2,4-triazole and its derivatives attracted synthetic and medicinal chemist due to various pharmacological potential like anxiolytic, [2][3][4][5] antibacterial, [6][7][8][9] anti-parasitic, [10] antiviral, [11] anti-oxidant, [12] fungicide, [13][14][15] antituberculosis, [16] antiepileptic, [17] antitumor. [18 -20] 1,2,4triazoles are derived from pyrazole via substituting doi.org/10.1002/cbdv.202200679 carbon by nitrogen atom at position 4, it acts as isosteres of ester, amide and carboxylic acid.…”