Aldehydes antiviral activity

Virus replication comprises numerous biochemieal transformations that might provide suitable targets for antiviral therapy. The antiviral effect of thiosemicarbazones was first demonstrated by Hamre et al. [53, 54], who showed that p-aminobenzaldehyde-3-thiosemicarbazone and several of its derivatives were active against vaccinia virus in mice. These studies were extended to include thiosemicarbazones of isatin, benzene, thiophene, pyridine, and quinoline derivatives, which also showed activity against vaccinia-induced encephalitis. The nature of the aldehyde/ketone moiety was not as significant as the presence of the thiosemicarbazide side chain the latter was deemed essential for antiviral activity. 

Davoodnia and coworkers set up a simple and efficient procedure for the synthesis of 14-aryl-147f-dibenzo[fl, ]xanthenes using a one-pot condensation reaction of P-naphthol and aryl aldehydes catalyzed by silica gel-supported polyphosphoric acid (PPA/SiOj) (Khojastehnezhad et al, 2011). Xanthene derivatives occupy a prominent position in medicinal chemistry (Wang et al., 1997) and have been investigated for their agricultural bactericide activity (Handique and Baruah, 2002), antiinflammatory effect (Sirkecioglu et al, 1995), and antiviral activity. 

The polyphenolic binaphthyl gossypol 94 displays interesting pharmacological applications like male oral contraceptive, treatment of bronchitis, total inhibitor of HIV 1, and in vitro antiviral activity against herpes type 2 virus and influenza virus (Scheme 26.28). Apogossypol 95, a degradation derivative of gossypol that lacks the aldehyde functions, still has the potent pan-active inhibitor activity of antiapoptotic Bcl-2 family proteins. The naphthoic acid precursor can be obtained by... 

A Cannizzaro reaction of a protected guanosine-5 -aldehyde was the key step In a synthesis of 4 -(hydro3qrmethyl)guanosine (44). which was devoid of antiviral activity. 9 ... 

Pharmacologically Active Compounds.— Benzo[6]thiophen-2- and -3-carbox-aldehyde thiosemicarbazones have been prepared and screened for antiviral activity. 3-Benzo[fe]thiophenoxyaminopropanols and the complex benzo[6]-... 

Various phosphorus compounds can be synthesized by P-H bond addition to unsaturated organic molecules (alkynes, alkenes, dienes, aldehydes and imines). The target products are in demand as biologically active compounds [8-26], useful compounds in nucleic acid chemistry [27-31], versatile reagents in synthesis [32-36] and building blocks in polymer sciences [37-43]. In the area of biologically active compounds antifungal and antibacterial properties of vinyl phospho-nates were considered as well as their anticancer and antiviral activity was evaluated [44 7]. Practical application includes utilization of phosphorus compounds in fuel cell membranes, optical materials and flame retardants [48-55]. 

Antischistosomal activity, of 5-nitro-2-aminothiazoles, 72 Antispasmodic activity, 150, 439 Antitrichomonal activity, 138 of 5-nitro-2-aminothiazoles, 72 Antitubercular activity, 139, 140,441,442 Antitumor activity, 149, 152 Antitussive, 144, 148 Antiulcer properties, 148 Antiviral, 138, 139, 140, 144,438 Appetite depressant, 147 Aprotic solvent, see Solvent effect Aromatic aldehydes, with aminothiazoles, 40... 

Further evidence for the importance of imine formation for T cell function was derived from the discovery that tucaresol and other small molecules with an aromatic aldehyde moiety capable of forming Schiff bases, produces a signal to CD4+ T helper (Th) cells [62]. Tucaresol reacts in vitro with free CD4+ T cell surface amines from receptors like CD2 within seconds to cause a co-stimulatory signal to produce a Thl response with the release of interferon y (IFN-y) and a 5- to 10-fold increase of interleukin 2 (IL-2). Such a Thl response is believed to be important for intracellular pathogens such as viruses, mycobacteria, protozoa and tumors. Studies in vivo show that low concentrations of tucaresol enhance not only CD4+ Th cells in response to antigens but also CD 8+ CTL and that this response has a beneficial effect in antiviral and antitumor therapy in animal models. Mechanistically, formation of Schiff bases with tucaresol has been shown to greatly affect intracellular potassium and sodium ion concentrations by the co-stimulation of mitogen-activated protein kinase (MAP kinase) and thus activation of ion channels in T cells [62,102]. Some of these mechanistic features are depicted in Fig. 19. 

These include the SSA-catalyzed synthesis of heterocyclic compounds such as xanthenes, coumarins, oxazoles, and so on. Xanthenes are of great therapeutic and biological interest on account of their many biological activities such as anti-inflanunatory, antiviral, antibacterial properties, and so on. Seyyed Hamzeh et al. (2008) carried out the SSA-catalyzed synthesis of aryl-14 f-dibenzo[fl,y]xanthenes from aldehydes and P-naphthol and 1,8-dioxo-octahydro-xanthenes from aldehydes and 1,3-dicarbonyl componnd such as dimedone under solvent-free conditions (Schemes 5.25, 5.26). Reactions were carried out at 80°C. Nazeruddin et al. (2011) documented an effective method for 9,10-dihydro-12-aryl-8 f-benzo[a]xanthenes-ll(12 f)-one derivatives in excellent yield and short reaction time using SSA under solvent-free conditions (Scheme 5.27). 

Various biological activities such as antimicrobial [111-113], antiviral [114], antidepressant [115], analgesic, and anti-inflammatory [116] have been recently reported for thienopyrimidine compounds. Mehdi et al. [117] developed a new iodine-catalyzed route for the synthesis of thieno[2,3-( pyrimidine derivatives 75 via heterocyclization of 2-amino-4,5-dimethylthiophene-3-carboxamide 74 with aromatic aldehydes (Scheme 10.55). 

Oxazoles are a common structural motif foxmd in numerous molecules that display antiviral, antifungal, antibacterial, and antiproliferative activities [150,151]. Classical methods for oxazole synthesis include Robinson-Gabriel synthesis by dehydration of 2-acylaminokefones, Fischer oxazole synthesis from cyanohydrins and aldehydes, Bre-dereck reaction with a-haloketones and formamide. Van Leusen reaction with aldehydes and TosMIC, Hantzsch reaction, and aza-Wittig reaction [152]. 

The macrolactins are a structurally diverse class of secondary metabolites isolated from a deep-sea bacterium. Macrolactin A exhibits a broad spectrum of activity with significant antiviral and cancer cell cytotoxic properties including inhibition of B16-F10 murine melanoma cell replication with in vitro IC50 values of 3.5 pg/mL. It also has implications for controlling human HIV replication and is a potent inhibitor of Herpes simplex types I and II. Marino and co-workers reported a stereocontrolled total synthesis of (-)-macrolactin A 107. Julia-Lythgoe olefmation was employed in the formation of C18-C19 double bond. ° The intermediate 105 was obtained in 78% yield by addition of sulfone 103 to aldehyde 102, benzolation of the adduct intermediate, and treatment with KOt-Bu. The alkene 106 was obtained in 56% yield with E/Z ratio of 8 2 by reduction of 105 using Sml2 in the presence of DMPU. 

Anticancer examples, Thiosemicarbazones have been mentioned above in connexion with their antiviral and antitubercular properties. They also have anticancer activity, as already mentioned for 5-hydroxypicolinic aldehyde thiosemicarbazone (4.18) in Section 4.0. Such substances powerfully inhibit ribonucleoside diphosphate reductase, the enzyme which converts ribo- to deoxyribo- nucleotides, leading to inhibition of DNA synthesis. Interaction with the enzymatically-required iron by these drugs in thought to lie at the root of their action (Agrawal, et al,y 1972). 

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