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We report the preparation of new C- and C-symmetrical molecules constructed on a triazine (TAZ) template. Anti-herpes simplex virus type 1 (anti-HSV-1) and cytotoxic activities against Vero cells of synthesized TAZ derivatives were evaluated. The results suggested that the presence of an electron-donating group(s) on the benzene ring in benzylamine groups on the TAZ template is an important structural factor for expressing a high level of anti-HSV-1 activity and low cytotoxicity for these C types of TAZ derivatives. Among the tested TAZ derivatives, compounds 4f and 7h showed the highest anti HSV-1 activities (EC=0.98 and 1.23 µM, respectively) and low cytotoxic activities to Vero cells (50% cytotoxic concentration (CC)=292.2 and >200 µM, respectively).

Mucolipidosis IV is a debilitating developmental lysosomal storage disorder characterized by severe neuromotor retardation and progressive loss of vision, leading to blindness by the second decade of life. Mucolipidosis IV is caused by loss-of-function mutations in the MCOLN1 gene, which encodes the transient receptor potential channel protein mucolipin-1. Ophthalmic pathology in patients includes corneal haze and progressive retinal and optic nerve atrophy. Herein, we report ocular pathology in Mcoln1(-/-) mouse, a good phenotypic model of the disease. Early, but non-progressive, thinning of the photoreceptor layer, reduced levels of rhodopsin, disrupted rod outer segments, and widespread accumulation of the typical storage inclusion bodies were the major histological findings in the Mcoln1(-/-) retina. Electroretinograms showed significantly decreased functional response (scotopic a- and b-wave amplitudes) in the Mcoln1(-/-) mice. At the ultrastructural level, we observed formation of axonal spheroids and decreased density of axons in the optic nerve of the aged (6-month-old) Mcoln1(-/-) mice, which indicates progressive axonal degeneration. Our data suggest that mucolipin-1 plays a role in postnatal development of photoreceptors and provides a set of outcome measures that can be used for ocular therapy development for mucolipidosis IV.

-We report the preparation of newly designed trivalent C 3 -symmetrical cyclic phenylboronic acid derivatives constructed on a symmetrical benzene or a cyclohexane ring. The synthesis of these C 3 -symmetrical molecules 4 was accomplished by an amide bond formation reaction using amino-substituted phenylboronic acid pinacol esters 2 and C 3 -symmetrical benzene-1,3,5-tricarboxylic acid trichloride 3a or cyclohexane-1,3,5-tricarboxylic acid trichloride 3b in the presence of Et 3 N. We confirmed that this procedure is conventionally applicable to the preparation of targeted C 3 -symmetrical cyclic boronic acid derivatives 4 in good to excellent yields. We also report the results of biological evaluation of the prepared compounds.Many host receptors that consist of homo-oligometric units (homo-multiligands) often construct symmetric macromolecule architectures such as C 2 -or C 3 -symmetrical geometry receptor systems.Molecular recognition of two-fold (C 2 ) or three-fold (C 3 ) geometric symmetrical macromolecules is one of the common features in several important biological processes. 1,2 With reference to the molecular symmetry, small oligovalent molecules having C 2 -or C 3 -symmetrical geometry have frequently appeared in various biologically active substances. [2][3][4] An oligovalent molecule is generally expected to show enhanced biological potential compared to that of the corresponding monovalent molecule. 4 On the other hand, regarding lectin-like carbohydrate recognition molecules, much attention has recently been paid to the design of synthetic receptors for carbohydrates. 5 We have been interested in small molecules that Figure 1). 9,10 From this point of view, we have recently synthesized a few 11 Figure 1As an extension of this study, we carried out further investigations of these symmetrical classes of compounds. In this paper, we report the synthesis of new trivalent C 3 -symmetrical phenylboronic acid derivatives incorporating a benzene or cyclohexane ring as a symmetrical template in the molecules and we report results of biological evaluations of the obtained C 3 -symmetrical phenylboronic acid derivatives.The results for synthesis of new C 3 -symmetrical cyclic boronic acid derivatives constructed on a benzene ring or a cyclohexane ring having three amide bonds are summarized in Tables 1 and 2. The synthesis of these target trivalent C 3 -symmetrical molecules 4aa~4ca constructed on a benzene ring was accomplished by an amide bond formation reaction using amino-substituted phenylboronic acid pinacol esters 2 and benzene-1,3,5-tricarboxylic acid trichloride 3a in the presence of a base such as Et 3 N. The preparation and physical and spectroscopic data of compounds 4aa~4ca have been reported in detail as a separated paper. 13 New C 3 -symmetrical compounds 4ab and 4bb constructed on a cyclohexane ring were also prepared by a procedure similar to that for compounds 4aa~4ca with cyclohexane-1,3,5-tricarboxylic acid trichloride in good yields (see EXPERIMENTAL). The structures of targe...