In terms of molecular symmetry and bioactivity, new C 3 -and C S -symmetrical derivatives based on the tris(2-aminoethyl)amine scaffold were designed and synthesized. The synthesized compounds were evaluated for antiviral activity with herpes simplex virus type 1 (HSV-1) by a plaque reduction assay and for cytotoxic activity with Vero cells. Most of the compounds showed no significant anti-HSV-1 activity, but some of the symmetrical derivatives showed high levels of cytotoxic activitiy.Key words tris(2-aminoethyl)amine; tripodal; anti-herpes simplex virus type 1; C 3 symmetry; C S symmetry; plaque reduction assay There have been many reports on the molecular recognition properties of symmetrical molecules, 1) and it is known that the symmetrical feature is frequently observed in many biological stages. Two-fold and three-fold symmetrical macromolecular structures are common features in specialized biological functions.2-4) Regarding the molecular symmetry, small symmetrical molecules with a C 2 -symmetrical or C 3 -symmetrical structure have often been found in various synthetic biologically active compounds. 5-7)In the course of our work on new antiviral compounds, we have presented a new class of antiviral candidates. For example, we have already reported that most of the triarylmethane derivatives showed a wide range of antiviral activities against herpes simplex virus type 1 (HSV-1). 8,9) In continuation with our work for finding potent antiviral derivatives, synthetic molecular modifications directed our attention to the molecular symmetry for the biological activity. Our recent studies on heteroaryl-substituted triarylmethane derivatives indicated that compounds bearing a prochiral symmetric feature (possessing C S symmetry) showed a higher level of antiviral activity than that of the corresponding C 3 -symmetrical molecules 9,10)

We investigated immunostained macrophages in the noninflamed mucosa of Crohn's disease patients. Biopsied specimens from endoscopically normal gastroduodenal mucosa of Crohn's disease, ulcerative colitis, and healthy control patients were studied. Sections were examined immunohistochemically using a monoclonal antibody specific for tissue macrophages (CD68). Immunostained mucosal macrophages in the second part of the duodenum, duodenal bulb, gastric antrum, and gastric body of the Crohn's disease group were more numerous than in the ulcerative colitis and control groups. The characteristic findings of Crohn's disease were aggregations, focal subepithelial dense accumulations, and infiltration throughout the mucosa of macrophages not accompanied by a lymphoid infiltrate. The number of macrophages in the gastroduodenal mucosa bore no relationship with the duration of symptoms, clinical activity, or affected site in the intestine. This suggests that the increased number of macrophages in noninflamed mucosa is a histological change characteristic for Crohn's disease that indicates a persistent latent abnormality involving the entire gastrointestinal tract.

We describe the synthesis and biological evaluation of newly designed 2,4,6-trisubstituted symmetrical 1,3,5-triazine (TAZ) derivatives. Among the tested trisubstituted symmetrical TAZ derivatives, various C 3 -or C S -symmetrical alkoxy-amino-substituted TAZ derivatives showed significant antiviral activity against herpes simplex virus type 1 (HSV-1) and/or cytotoxic activity against Vero cells. The structure-activity relationships for anti-HSV-1 activity of these symmetrical 2,4,6-trisubstituted TAZ derivatives are also described. Experimental results indicated that a C S -symmetrical TAZ structure with introduction of two alkoxy groups and one amine moiety seems to be the minimally required structure for anti-HSV-1 activity.Key words 1,3,5-triazine; anti-herpes simplex virus type 1; cytotoxic activity; C 3 symmetry; C S symmetry; plaque reduction assay Molecular recognition of two-fold (C 2 ) or three-fold (C 3 ) symmetrical geometry macromolecules is one of the common features in many important biological responses, 1,2) and we have therefore already designed a few symmetrical target molecules for the purpose of finding biologically active new leads or candidates.3-5) With reference to the molecular symmetry, small molecules having C 3 -, C S -, or C 2 -symmetrical geometry frequently appear in various biologically active compounds. [6][7][8] Such small symmetrical molecules are usually constructed on a corresponding symmetrical template.From this point of view, we have recently reported some molecular modifications of tris(2-aminoethyl) amine (TAEA) derivatives to C 3 -or C S -symmetrical tripodal receptor type molecules and the results of biological evaluation of these symmetrical compounds.3) We have also reported an interesting lectin-like property for sugar recognition of some of these tripodal receptor type TAEA molecules. 4)In order to achieve a suprafacial three-dimensional interaction of a bioactive symmetrical molecule for its binding site, the nature of substituents in the molecule is thought to be very important for preferential interactions. Such interactions are dictated largely by van der Waals interactions or formation of hydrogen bonds. The introduction of amine (basic nitrogen atom) and/or a bivalent oxygen group such as a hydroxy or alkoxy group into a C 3 -symmetrical 1,3,5-triazine (TAZ) template seems to be interesting, because it is well known that amine functionalities behave as both hydrogen acceptors and hydrogen donors in appropriate circumstances. These facts may indicate that molecules with some amine and/or bivalent oxygen functionalities on a heterocyclic C 3 -symmetrical TAZ template can produce a property for suprafacial hydrogenbonding interaction.For an extension of our studies, we planned to investigate the synthesis of 2,4,6-trisubstituted symmetrical TAZ derivatives [9][10][11][12][13][14][15][16] as well as to evaluate their biological properties. In this paper, we report the results of new synthetic routes for C 3 -or C S -symmetrical 2,4,6-trisubstituted TAZ derivativ...

The ability to diagnose obscure fistulas using the indocyanine green test was 92 percent. This indocyanine green test was highly diagnostic, whereas conventional examinations are often complicated and much less diagnostic.