Synthetic Compounds with 2-Amino-1,3,4-Thiadiazole Moiety Against Viral Infections

Abstract

Viral infections have resulted in millions of victims in human history. Although great efforts have been made to find effective medication, there are still no drugs that truly cure viral infections. There are currently approximately 90 drugs approved for the treatment of human viral infections. As resistance toward available antiviral drugs has become a global threat to health, there is an intrinsic need to identify new scaffolds that are useful in discovering innovative, less toxic and highly active antiviral agents. 1,3,4-Thiadiazole derivatives have been extensively studied due to their pharmacological profile, physicochemical and pharmacokinetic properties. This review provides an overview of the various synthetic compounds containing the 2-amino-1,3,4-thiadiazole moiety that has been evaluated for antiviral activity against several viral strains and could be considered possible prototypes for the development of new antiviral drugs.Molecules 2020, 25, 942 2 of 22 due to the ability of viruses to undergo rapid mutations, the mechanisms involved in developing resistance to antiviral drugs are activated in most cases [1,3]. As resistance toward antiviral drugs is becoming a global health threat, there is an intrinsic need to identify new scaffolds that are useful in discovering innovative, less toxic and highly active antiviral agents [3,6,7]. Nitrogen-Containing Heterocycles and Thiadiazole Ring in Biology and Medicinal ChemistryNitrogen-containing heterocycles are widely distributed in nature and are essential in vegetal and animal metabolism. They are found in nucleic acids, vitamins, antibiotics, alkaloids, etc. [8][9][10][11][12][13][14]. In addition, nitrogen-containing heterocycles are important targets for medicinal chemistry, as they are found in more than half of the commercially available drugs and can also act as versatile intermediates in the synthesis of complex products that exhibit outstanding biological activities [15]. Most of the nitrogen-containing heterocyclic compounds exhibit better biological activity than non-nitrogen compounds [12,16,17]. Currently, there are approximately 90 drugs approved for use in the treatment of nine human viral infections caused by human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), Influenza virus, human cytomegalovirus (HCMV), varicella-zoster virus (VZV), respiratory syncytial virus (RSV) and human papillomavirus [18]. Most of these drugs (e.g., acyclovir, cidofovir, idoxuridine, nevirapine, pleconaril, ribavirin, etc.) are nitrogen heterocycle molecules [3,19].Five-membered aromatic systems with three heteroatoms at symmetrical positions, such as the 1,3,4-thiadiazole ring, have been extensively studied due to their pharmacological profile and physicochemical and pharmacokinetic properties. 1,3,4-Thiadiazole derivatives are known as compounds having significant and diverse biological activities such as antibacterial, antifungal, antitubercular [20], analgesic and anti-inflammatory [21,22], antidepr...

2-Amino-1,3,4-Thiadiazole Derivatives as Potential Anti-Helicobacter Pylori Agents – At a Glance

“…In addition, 2-amino-1,3,4thiadiazole derivatives with antitumour and uricogenic potential have been reported [7,13,18,43]. We already presented some 2-amino-1,3,4-thiadiazoles with antimicrobial [25,29], anti-leishmanial [27], antitrypanosomal, antimalarial, antitoxoplasmosis [30] and antiviral activities [31]. This mini-review describes 2-amino-1,3,4-thiadiazole derivatives that exhibit anti-H. pylori activity.…”

1,3,4-Thiadiazole Scaffold: As Anti-Epileptic Agents

“…The molecular structure of a compound is responsible for various pharmacological activities, and mostly heterocyclic moieties have diverse activities. This scaffold (Figure 1A) derivatives possess a wide range of biological activities such as anticancer/antitumor (Janowska et al, 2020;Cevik et al, 2020;Gomha et al, 2017;Flefel et al, 2017;Ningegowda et al, 2017), anticonvulsant (Khatoon et al, 2018;Bhandari et al, 2008;Jatav et al, 2008;Foromadi et al, 2007;Almasirad et al, 2007;Dawood et al, 2006;Dogan et al, 2002;Varvaresou et al, 1998;Khazi et al, 1996;Stillings et al, 1986;Chapleo et al, 1986), antidiabetic (Vaishnav et al, 2017;Datar and Deokule, 2014;Thrilochana et al, 2014), anti-inflammatory (Cristina et al, 2018;Schenone et al, 2006), antidepressant (Can et al, 2012), antihypertensive (Samel and Pai, 2010), antiviral (Serban et al, 2020;Brai et al, 2019), antimicrobial (Gowda et al, 2020;Merugu et al, 2020;Mutchu et al, 2019;Sekhar et al, 2018;Joseph et al, 2015), antioxidant (Yakan, 2021;Gowda et al, 2020), anti-leishmanial (Tahghighi and Babalouei, 2017;Sadat-Ebrahimi et al, 2019), and neuroprotective (Skrzypeka et al, 2021). The biological activities of several synthesized derivatives of 1,3,4-thiadiazole are based on assumptions like "the N-C-Smoiety's presence and strong aromaticity of the ring, which is responsible for providing low toxicity and great in vivo st...…”

A competitive reactivity study on the oxidative cyclization of thiosemicarbazones into 1,3,4-thiadiazoles

“…The synthesis of the 1,3,4-thiadiazole ring has seen quite some interest, because this framework is present in various bioactive molecules, [1][2][3][4] useful in particular as antimicrobial [5][6][7][8][9][10][11] and antitumor [12][13][14][15] agents. A typical synthetic approach is constituted by the cyclization of ketone thiosemicarbazones, which easily affords C(2)saturated and spiro-type 1,3,4-thiadiazolidine derivatives.…”