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Since time immemorial human beings have constantly been fighting against viral infections. The ongoing and devastating coronavirus disease 2019 pandemic represents one of the most severe and most significant public health emergencies in human history, highlighting an urgent need to develop broad‐spectrum antiviral agents. Salicylamide (2‐hydroxybenzamide) derivatives, represented by niclosamide and nitazoxanide, inhibit the replication of a broad range of RNA and DNA viruses such as flavivirus, influenza A virus, and coronavirus. Moreover, nitazoxanide was effective in clinical trials against different viral infections including diarrhea caused by rotavirus and norovirus, uncomplicated influenza A and B, hepatitis B, and hepatitis C. In this review, we summarize the broad antiviral activities of salicylamide derivatives, the clinical progress, and the potential targets or mechanisms against different viral infections and highlight their therapeutic potential in combating the circulating and emerging viral infections in the future. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Novel salicylamide derivatives were synthesized. • Most compounds showed selective AChE inhibitory and significant antioxidant activities. • Some compounds exhibited good inhibition of self- or Cu2+-induced A β aggregation. • Some compounds exhibited moderate effect on the disaggregation of A β aggregation. • Compound 15b showed good anti-neuroinflammation activity and BBB permeability. Abstract A series of salicylamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors. They showed good inhibitory activities of self- and Cu2+-induced A β 1–42 aggregation, and significant antioxidant activities. Among them, compound 15b exhibited good inhibitory activity toward Rat AChE and Ee AChE with IC 50 value of 10.4 μM and 15.2 μM, respectively. Moreover, 15b displayed high antioxidant activity (2.46 Trolox equivalents), good self- and Cu2+-induced A β 1–42 aggregation inhibitory potency (42.5% and 31.4% at 25.0 μM, respectively) and moderate disaggregation ability to self- and Cu2+-induced A β 1–42 aggregation fibrils (23.4% and 27.0% at 25 μM, respectively). Furthermore, 15b also showed biometal chelating abilities, anti-neuroinflammatory ability and BBB permeability. These multifunctional properties indicated compound 15b was worthy of being chosen for further pharmacokinetics, toxicity and behavioral researches to test its potential for AD treatment. [ABSTRACT FROM AUTHOR]

Abstract: Three series of salicylanilides, esters of N-phenylsalicylamides and 2-hydroxy-N-[1-(2-hydroxyphenylamino)-1-oxoalkan-2-yl]benzamides, in total thirty target compounds were synthesized and characterized. The compounds were evaluated against seven bacterial and three mycobacterial strains. The antimicrobial activities of some compounds were comparable or higher than the standards ampicillin, ciprofloxacin or isoniazid. Derivatives 3f demonstrated high biological activity against Staphylococcus aureus (⩽0.03μmol/L), Mycobacterium marinum (⩽0.40μmol/L) and Mycobacterium kansasii (1.58μmol/L), 3g shows activity against Clostridium perfringens (⩽0.03μmol/L) and Bacillus cereus (0.09μmol/L), 3h against Pasteurella multocida (⩽0.03μmol/L) and M. kansasii (⩽0.43μmol/L), 3i against methicillin-resistant S. aureus and B. cereus (⩽0.03μmol/L). The structure–activity relationships are discussed for all the compounds. [Copyright &y& Elsevier]

A series of novel salicylamide derivatives containing neonicotinoid pharmacophore were designed and synthesized via multi-step reactions. These compounds were characterized by satisfied spectrum analyses mainly including H NMR and ESI-MS. The preliminary bioassays indicated that some of target compounds exhibited excellent insecticidal activities against Heliothis armigera and Plutella xylostella at the dosage of 31.25 μg/mL. [ABSTRACT FROM AUTHOR]

A new series of pyridazine, pyrazoles, pyrazolidine-3,5-dione, Semicarbazide, thiosemicarbazides, hydantoin, thiohydantoins, 1,2,4-triazoles, S-triazolo[3,4-b]-1,3,4-thiadiazoles incorporated indirectly into salicylamide moiety at position 2 were synthesized. Also the synthesis of novel series of 3-salicylamido-2-hydroxypropyl-amine derivatives were prepared. Several of these compounds were screened for antiinflammatory, analgesic, antipyretic and ulcerogenic activities. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of 5-chloro-2-hydroxybenzamides was discovered as potent RSV inhibitors. • Several molecules suppressed both RSV viral replication and associated cytokines. • Two selected compounds inhibited RSV-induced IRF3 and NF-κB activation. • These potential anti-inflammatory agents may alleviate RSV-associated symptoms. Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children, and specific treatment for RSV infections remains unavailable. We herein reported a series of substituted N -(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent RSV inhibitors. Among them, six low cytotoxic compounds (11 , 12 , 15 , 22 , 26, and 28) have been identified and selected to study associated inhibitory mechanisms. All these compounds suppressed not only the viral replication but also RSV-induced IRF3 and NF-κB activation and associated production of cytokines/chemokines. The two most potent compounds (15 and 22) were selected for further molecular mechanism studies associated with their suppression effect on RSV-activated IRF3 and NF-κB. These two compounds decreased RSV-induced IRF3 phosphorylation at serine 396 and p65 phosphorylation at serine 536 at both early and late infection phases. In addition, compound 22 also inhibited RSV-induced p65 phosphorylation at serine 276 at the late phase of RSV infection. [ABSTRACT FROM AUTHOR]

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI. [ABSTRACT FROM AUTHOR]