Preparation and Antiviral Activity of Some New <i>C</i>₃- and <i>C_S</i>-Symmetrical Tri-Substituted Triazine Derivatives Having Benzylamine Substituents

Abstract

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).

Preparation of Some Novel Trisubstituted 1,3,5-Triazines and Hybrid Linker Mode 1,3,5-Triazine Derivatives and Their Biological Evaluation

“…As can be seen in Tables 1 and 2, the yields in the procedure (entries 1~11) with the starting TCTAZ (1) to target CS-symmetrical TAZ derivatives (4 and 7) were good, and this method for synthesis of TAZ derivatives was reproducible and was reconfirmed to be useful as a general procedure for synthesis of trivalent TAZ derivatives. 12 The presence of a phenylethylamino functionality in the CS-type TAZ molecules (7) also gave a good result. The structures of the obtained new trivalent TAZ derivatives (4 and…”

“…The reason for no activity of compound 4bc (EC50 > 100 and CC50 > 200 μM) is not clear. (8,10,12,14,16,19) and related compounds (11 and17) activity was slightly lower than that of the C3-type trivalent original molecules (A and B). The results for other hybrid-type compounds are also shown in Table 5.…”

“…On the basis of the information obtained by the evaluation of biological activities of the tri-substituted TAZ derivatives and hybrid-type multivalent mid-size series together with recent information on the C3-type TAZ series, 12,13 we are now investigating further molecular modifications of these TAZ derivatives (4ab and 10aq) with the aim of developing new synthetic compounds with anti-HSV-1 activity.…”

“…4 To develop new multivalent symmetrical bioactive compounds or leads, we have recently designed and synthesized a few new molecules with such geometry and evaluated their bioactivities in order to find new types of bioactive leads. [5][6][7][8][9][10][11][12][13][14] In connection with this project, we have recently reported the preparation of various C3-symmetrical trivalent 1,3,5-triazine (TAZ) derivatives and the results of biological evaluation of the synthesized symmetrical TAZ derivatives. 7,12 Among previously targeted C3-symmetrical TAZ derivatives, we found that C3-symmetrical tri-substituted TAZ derivatives (A and B) showed high levels of anti-HSV-1 activity (EC50 = 0.98 and 1.87 μM, respectively) and considerably low levels of cytotoxic activity (CC50 > 200 μM) against Vero cells, 7,12 and these TAZ derivatives are considered to be potential new leads in the search for antiviral active molecules (Figure 1).…”

“…[5][6][7][8][9][10][11][12][13][14] In connection with this project, we have recently reported the preparation of various C3-symmetrical trivalent 1,3,5-triazine (TAZ) derivatives and the results of biological evaluation of the synthesized symmetrical TAZ derivatives. 7,12 Among previously targeted C3-symmetrical TAZ derivatives, we found that C3-symmetrical tri-substituted TAZ derivatives (A and B) showed high levels of anti-HSV-1 activity (EC50 = 0.98 and 1.87 μM, respectively) and considerably low levels of cytotoxic activity (CC50 > 200 μM) against Vero cells, 7,12 and these TAZ derivatives are considered to be potential new leads in the search for antiviral active molecules (Figure 1). Regarding the carbohydrate recognition property of TAZ derivatives with high anti-herpes simplex virus type 1 (anti-HSV-1) activity, the results of our thermodynamic experiments indicated that the C3-type TAZ derivative (A) having a benzylamine group is a more promising antiviral lead than the C3-type trialkoxy-substituted TAZ derivative (B).…”