Antiviral activity, relationship

G. D. Kini, J. R. Beadle, K. A. Aldern, K. Y. Hostetler, Propanediol Phospholipid Prodrugs of Foscarnet (PFA) Synthesis and Structure-Antiviral Activity Relationships , in Abstracts of the 211th American Chemical Society National Meeting, Division of Medicinal Chemistry , New Orleans, LA, March 24-28, 1996, Abstract No. 172. 

Kuz min VE, Artemenko AG, Polischuk PG et al (2005) Hierarchic system of QSAR models (ID D) on the base of simplex representation of molecular structure. JMol Model 11 457-467 Kuz min VE, Artemenko AG, Lozitsky VP et al (2002) The analysis of structure-anticancer and antiviral activity relationships for macrocyclic pyridinophanes and their analogues on the basis of 4D QSAR models (simplex representation of molecular structure). Acta Biochim Pol 49 157-168... 

Substituted nitro derivatives of azoIo[5,l-c][l,2,4]triazines were examined for their antimicrobial activity. They displayed antibacterial, antifungal, and antiviral activities. Structure-reactivity relationships have been reported (90KFZ39). 

Kim CU, Lew W, Wilhams MA, Wu H, Zhang L, Chen X, Escarpe PA, Mendel DB, Laver WG, Stevens RC (1998) Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors, J Med Chem 41 2451-2460 Kim CU, Chen X, Mendel DB (1999) Neuraminidase inhibitors as anti-influenza virus agents. Antiviral Chem Chemother 10 141-154... 

Following the discovery of the antiviral activity of the azidothymidine analog, and the activity of the 3 -azido-2 -dideoxyguanosine analog [262], the synthesis of a series of 2-amino-6-substituted-(3 azido-2, 3 -dideoxy-b-D-eryfhro-pento-furanosyl)purine analogs 196 was undertaken to explore the structure-activity relationships. 

Drug binding is enhanced by hydrophobicity in that portion of the drug that binds to the pocket toe. Quantitative structure-activity relationship (QSAR) analysis of these compounds have consistently shown that the most predictive parameter of antiviral activity is a measure of hydrophobicity, the octanol water partition coefficient (logP) [80,82,85]. These studies have also consistently shown that there is no apparent correlation between electrostatic potential or dipole moment and potency. 

The cytotoxicity and antiviral activity of distamycin derivatives containing 2, 3, 4 and 5 pyrrole rings is shown in Table 1. The cytotoxicity of the derivatives with 2 and 3 pyrrole residues is the same. However, compounds containing 4 and 5 pyrrole rings (distamycin/4 and distamycin/5) are less toxic. The cytotoxicities of distamycin/4 and distamycin/5 are only 50% and 25% of the natural antibiotic (distamycin/A) respectively. It seems therefore, that the cytotoxicity decreases as the number of pyrrole rings increases. This is at least true for distamycin/A, distamycin/4 and distamycin/5. Our studies on dista-mycin/6 (distamycin with 6 pyrrole rings) have, however, shown that no such relationship strictly exists. Distamycin/6 was found to be as toxic as distamycin/4. 

The dihydro-chloride salt of 2,7-bis(2-(diethylamino)ethoxy)-fluoren-9-one, referred to as tilorone hydrochloride (non-proprietary name) or bis-DEAE-fluorenone, is a broad spectrum antiviral compound44) with antitumor activity45-47). Mayer and coworkers48 49) have identified this compound as an interferon inducer and established a relationship with the antiviral activity. However, recently a lack of correlation between interferon induction and viral protection by tilorone hydrochloride has been reported50). 

A sensitive method to measure toxic effects of drugs is to monitor cellular metabolism by incorporation of 3H-thymidine or 14C-protein hydrolysate. 14C-protein is used in preference to 3H-thymidine when it is necessary to avoid competition in uptake between the labeled thymidine and an unlabeled nucleoside reverse-transcriptase inhibitor. These methods are used mainly to monitor sublethal toxicity after initial screening or when comparing structure-activity relationships. The assays described here are carried out using 6-mL culture tubes (Note 1). These assays are carried out in parallel with the antiviral assay. 

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