N-long-chain monoacylated derivatives of 2,6-diaminopyridine with antiviral activity.

N-Monoacyl-2,6-diaminopyridines (2a-c) and N,N'-diacyl-2,6-diaminopyridines (3a-c) were synthesized from 2,6-diaminopyridine by acylation with the corresponding acyl halide or by dehydration with the corresponding carboxylic acid using 1,3-dicyclohexylcarbodiimide (DCC). The antiviral activities of N-monoacyl- and N,N'-diacyl-2,6-diaminopyridines (2a-c and 3a-c) were estimated using plaque reduction assay with HSV-1. All N-monoacyl derivatives (2a-c) showed significant anti-herpes simplex virus (HSV)-1 activity (EC(50) = 15.

Synthesis and antiviral activities of some 4,4'- and 2,2'-dihydroxytriphenylmethanes.

We synthesized some 4,4'- and 2,2'-dihydroxytriphenylmethane derivatives 3a--e and 4a--c by condensation of phenol 1 and aromatic aldehyde 2 in moderate to good yields (30--83%). Most of them showed significant antiviral activity against herpes simplex virus type 1 (anti-HSV-1 activity) in a plaque reduction assay. The most potent antiviral activity (EC(50)=0.

Anti-herpes virus type 1 activity of oleanane-type triterpenoids.

The anti-herpes simplex virus type 1 (HSV-1) activity of 15 oleanan-type triterpenoides including glycyrrhizin and its sapogenol was examined and their structure-activity relationships were discussed. Although glycyrrhizin which exhibited in vivo efficacy against HSV-1 replication showed moderate in vitro anti-HSV-1 activity, its sapogenol, glycyrrhetic acid, showed 10 times greater action than glycyrrhizin. Therefore, the in vivo anti-HSV-1 activity of glycyrrhizin administered orally could be reasonably attributed to glycyrrhetic acid generated by hydrolysis by intestinal bacteria.

A new lignan glycoside and phenylethanoid glycosides from Strobilanthes cusia BREMEK.

The root of Strobilanthes cusia BREMEK. (Acanthaceae), popularly known as Da-Ching-Yeh, has been commonly used in traditional Chinese medicine. It is used to treat influenza, epidemic cerebrospinal meningitis, encephalitis B, viral pneumonia, mumps, and severe acute respiratory syndrome (SARS).

[Metabolites produced by actinomycetes--antiviral antibiotics and enzyme inhibitors].

In 1995, we discovered new antiherpetic antibiotics, called fattiviracins. The producing organism was classified as a strain belonging to Streptomyces microflavus. The strain produced at least 13 fattiviracin derivatives (FV-1 to FV-13).

Inhibitory activities against topoisomerase I and II by polyhydroxybenzoyl amide derivatives and their structure-activity relationship.

o-, m-, p-Phenylenediamines having 2,3,4-trihydroxy, 3,4 dihydroxy, and 4-hydroxybenzoyl moieties were prepared and their inhibitory activities were measured against topoisomerase I and II. More hydroxy groups on two aromatic rings increased the activities. Bis(trihydroxybenzoyl)-o-phenylenediamide showed IC(50)=0.

2070-DTI, a topoisomerase inhibitor produced by Streptomyces sp. strain No. 2070.

A novel inhibitor of topoisomerase II designated as 2070-DTI was isolated from the culture filtrate of Streptomyces sp. strain No. 2070.

Synthesis and antiviral activities of some 4,4'-dihydroxytriphenylmethanes.

4,4'-Dihydroxytriphenylmethanes were synthesized using Brønsted acid or Lewis acid in yields of 24-86% as target compounds for developing antiviral agents. Most of the 4,4'-dihydroxytriphenylmethanes showed significant activity against herpes simplex virus type 1 (anti-HSV-1 activity) in a plaque reduction assay. Higher cytotoxicity was observed generally in halogenated 4,4'-dihydroxytriphenylmethanes (2a-d) than in non-halogenated derivatives.

Inhibition of hyaluronidases and chondroitinases by fatty acids.

The inhibitory effects of various fatty acids on three hyaluronidases (h-ST, h-SH and h-SD) and four chondroitinases (c-ABC, c-B, c-ACI and c-ACII) were examined, and their structure-activity relationships and mechanism of action were studied. The fatty acids used in this experiment showed various inhibitory activities against the enzymes. None of the fatty acids did not inhibit h-ST and h-SH.

Inhibitory properties of antitumor prostaglandins against topoisomerases.

Prostaglandins (PGs) having antitumor activity such as delta12,14-PGJ2, delta12-PGJ2, PGA2 and PGA1 strongly inhibited topoisomerase II (topo II) from human placenta, the potential order of inhibitory activity of the PGs resembling that of the antitumor activity. PGs having no antitumor activity did not inhibit topo II. Delta12,14-PGJ2 to be a potent inhibitor showed inhibitions to some extent against topo I from wheat germ, NIH3T3 and calf thymus gland, and showed no inhibition against the enzymes from Vero, A549, HeLa and COLO 201 cells.

Synthesis of 2,2'-dihydroxybisphenols and antiviral activity of some bisphenol derivatives.

New diphenylmethane-type 2,2'-dihydroxybisphenols (5a-d) were prepared regioselectively in good yields. We evaluated the antiviral activity of some bisphenol derivatives synthesized by the plaque reduction assay. Most of the compounds showed significant antiviral activity and the 4,4'-dihydroxybisphenol derivative (10) showed higher activity than 2,2'-bisphenol derivatives.