Novel bivalent twin-drug type hydantoin derivatives were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the 5-substituted hydantoin ...derivatives (1a–b and 2a–d) examined in this study, bivalent symmetrical 5-substituted hydantoin derivative 1b showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of anti-proliferative activity (IC50) of this hydantoin derivative against the two cell lines (U251 and KB3-1) were 0.46 and 5.21 µM, respectively. The anti-proliferative activity of all of the compounds except for compounds 2a and 2d against U251 cells was higher than that of cisplatin. Bivalent symmetrical compound 1b had a biphenylmethane linker in the molecule. All of the tested bivalent hydantoin derivatives showed higher activity against U251 cells than against KB3-1 cells. For twin-drug type hydantoin derivatives 2a–d, which have a linear methylene linker in the molecules, it was found that methylene linker length in these molecules have an effect on the anti-proliferative activity against U251 and KB3-1 cells.
Derivatives of C2-symmetrical bivalent phenylboronic acid exhibit several remarkable biological activities such as anti-herpes simplex virus (HSV)-1 and cytotoxic activities against Vero cells and ...they can reverse the effect of anticancer drugs. Novel symmetrical bivalent molecules were synthesized and their biological activities were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the tested compounds (1a–i), bivalent C2-symmetrical phenylboronic acid derivative 1g showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of 50% anti-proliferative activity (IC50) of this compound against the two cell lines (U251 and KB3-1) were 19.0 and 3.78 µM, respectively. The anti-proliferative activity of compound 1g towards KB3-1 cells was higher than that of cisplatin. The bivalent C2-symmetrical compound 1g had a linear methylene linker in the molecule.
We report the preparation of new C3- and CS-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 C3 types of TAZ derivatives. Among the tested TAZ derivatives, compounds 4f and 7h showed the highest anti HSV-1 activities (EC50=0.98 and 1.23 µM, respectively) and low cytotoxic activities to Vero cells (50% cytotoxic concentration (CC50)=292.2 and >200 µM, respectively).
We report the preparation of new tripodal receptor-type C3- and CS-symmetrical molecules constructed on a tris(2-aminoethyl)amine (TAEA) template. Both the anti-herpes simplex virus type 1 ...(anti-HSV-1) activity and cytotoxic activity of synthesized receptor-type derivatives were evaluated in order to find a characteristic structural feature for these bioactivities of compounds. Among the compounds of synthesized symmetrical TAEA-related derivatives, compound 13k showed high anti-HSV-1 activity (50% effective concentration (EC50)=16.7 µM) and low cytotoxicity (50% cytotoxic concentration (CC50)=>200 µM). The presence of a hydrogen bond donor proton in the molecule is thought to be an important structural factor for expressing potential anti-HSV-1 activities.
In connection with our studies on hydantoin derivatives, a conventional regioselective chemical transformation of 5-methylene hydantoins 4a–c to 5-aminomethyl-substituted hydantoins 5–10 or to ...5-amino-5-methyl-disubstituted hydantoins 11–14 is described. Synthesis of bivalent twin-drug type hydantoin derivatives 19–24 and the binding property of a bivalent symmetrical hydantoin derivative 24b to sulfated glycosaminoglycans are also described.
As one of our projects, we here report some new molecular modifications of 2,4,6-trichloro-1,3,5-triazine (TCTAZ: 1) to symmetrical 2,4,6-trialkoxy- or 2,4,6-triaryloxy-substituted 1,3,5-triazine ...(TAZ) molecules, as well as the results of anti-herpes simplex virus type 1 (anti-HSV-1) activity evaluation of synthesized 2,4,6-trisubstituted TAZ derivatives. Among the tested 2,4,6-trisubstituted TAZ derivatives, we reconfirmed that a C3-symmetrical TAZ derivative, 4e, shows the highest level of anti-HSV-1 activity with a good selectivity index. In this paper, we also report the results of the preparation of newly targeted TAZ derivatives and the structure–activity relationships (SARs) of these trialkoxy-substituted TAZ derivatives and related compounds. The sugar recognition properties of C3-symmetrical TAZ derivative 4e are also described.
In connection with our studies on antibacterial compounds in the class of 5-dialkylaminomethylhydantoins against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains, ...some molecular modifications were attempted. The antibacterial activities of all of the synthesized hydantoin derivatives were evaluated. Among the hydantoin derivatives designed in this study, C2-symmetrical twin-drug type compound (7) showed the highest level of antibacterial activity against S. aureus strain.
Interactions between carbohydrate-containing glycoproteins, proteoglycans, and glycolipids on the cell surface are important biological stages for the processes of bacterial or viral infection and ...tumor metastasis. Moreover, supramolecular interaction by macromolecules with two-fold (C2) or three-fold (C3) geometry is one of the common interactions in many important biological responses. To develop new multivalent symmetrical bioactive compounds or leads, we designed and synthesized several new molecules with these geometries and evaluated their bioactivities in an attempt to find new types of bioactive leads that may interfere with the sugar recognition process. We evaluated bioactivities including antibacterial, antiviral, and anticancer activities of targeted molecules in vitro using biological assay systems. Among the synthesized target derivatives examined, some bivalent symmetrical derivatives showed high levels of bioactivities. In this review, the author describes the results of synthesis of oligovalent symmetrical target compounds and some interesting guiding results of evaluation of their biological activities and structure-activity relationships.
PDF
