Antiviral Activity of Substituted Salicylanilides - A Review

Abstract

Chemotherapy of viral infections is still challenging. Salicylanilides demonstrated a wide range of biological activities including antiviral potency and the review summarizes this field. Niclosamide was described to be able to affect coronaviruses. Some salicylanilides and salicylamides could inhibit HIV virus by targeting of HIV-1 integrase or reverse transcriptase. Hepatitis C virus is another virus, which could be potentially afflicted by salicylanilides on the level of two enzymes--NS3 protease and NS5B RNA polymerase. Nitazoxanide is a nitrothiazole derivative of salicylamide useful for the treatment of protozoal and bacterial infections with an extended range of antiviral activity and innovative mechanism of action, especially against hepatitis and influenza viruses or rotaviruses. Nitazoxanide, its metabolite tizoxanide and their derivatives are a very promising stream in the development of new antiviral compounds. In this review, we summarize the antiviral activity of structures containing salicylanilide and partly salicylamide moiety.

Antiviral mechanisms of candidate chemical medicines and traditional Chinese medicines for SARS-CoV-2 infection

“…Another compound is niclosamide, which is an FDA-approved anthelminthic drug against tapeworm infections for several decades (Xu et al, 2020a). It is a multifunctional drug that can inhibit oxidative phosphorylation and stimulate adenosine triphosphatase activity in the mitochondria, regulate multiple signaling pathways and biological processes, including Wnt/β-catenin, mTORC1, STAT3, NF-κB, Notch, NS2B-NS3 interaction, and pH (Kratky and Vinsova, 2011;Pindiprolu and Pindiprolu, 2020;Xu et al, 2020a). These results suggest that niclosamide has broad-spectrum antiviral activities.…”

“…These results suggest that niclosamide has broad-spectrum antiviral activities. Furthermore, the derivatives of niclosamide, such as 2-chloro-4-nitroanilide, O-alkylamino-tethered, or salicylamide derivatives, also exhibit more potent and orally bioavailable for antiviral treatments (Kratky and Vinsova, 2011;Xu et al, 2020a). Moreover, niclosamide may inhibit endocytosis of SARS-CoV-2 by blocking ACE2, and prevent autophagy of SARS-CoV-2 by inhibiting of S-Phase kinase-associated protein 2 (Pindiprolu and Pindiprolu, 2020).…”

B3LYP Study of 3-hydroxynaphthalene-2-carboxanilide para-derivatives

“…2). After exclusion of the data for -NO 2 and -F substituents, we have obtained the linear function with R = 0.91 MIC / μmol L -1 = -519(120) × DFT-logP + 2135(354) (5) In general, the antimycobacterial activity of potential drugs is very often affected by the differences in the permeability of the cell walls. Although all investigated compounds have the planar 1a conformation, their penetration into bacterial cells can be supported by their higher electric dipole moments together with the size of the terminal substituent.…”

“…3,4 These N-substituted hydrox ybenzamides represent compounds with a wide range of pharmacological activities. 5,6 The exact mechanism of action is still under investigation, but these compounds are known to act as inhibitors of protein kinase epidermal growth factor receptor. 7 Moreover, the salicylanilides were also found to inhibit bacterial enzymes.…”

Antifungal Activity of Salicylanilides and Their Esters with 4-(Trifluoromethyl)benzoic Acid

“…Salicylanilides (2-hydroxy- N -phenylbenzamides) have displayed a wide range of potentially interesting biological effects including those against protozoa, fungi, bacteria and mycobacteria or viruses [ 5 , 6 ]. Their mechanism of the action towards microbes is believed to be multiple, with a lot of molecular targets and effects [ 7 ].…”