Anti-herpes Virus Type 1 Activity of Oleanane-Type Triterpenoids

Ikeda, Tsuyoshi; Yokomizo, Kazumi; Okawa, Masafumi; Tsuchihashi, Ryota; Kinjo, Junei; Nohara, Toshihiro; Uyeda, Masaru

doi:10.1248/bpb.28.1779

Cited by 87 publications

(72 citation statements)

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“…Antiviral Activity and Discussion Synthesized TAZ derivatives were evaluated for anti-HSV-1 activities by plaque reduction assays 25) and were also evaluated for their cytotoxicities against Vero cells. The results are summarized in Table 3, and aciclovir 26) is also shown as a positive control. Calculated log P values for the compounds are also shown in Table 3.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Symmetrical 2,4,6-Trisubstituted 1,3,5-Triazine Derivatives

et al. 2013

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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...

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Section: Resultsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Symmetrical 2,4,6-Trisubstituted 1,3,5-Triazine Derivatives

et al. 2013

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“…When orally administered, before absorption, human intestinal bacteria completely convert glycyrrhizin to its aglycone metabolite glycyrrhetinic acid (16), which exhibits higher bioactivity than its precursor (17). Like glycyrrhizin, glycyrrhetinic acid can exist as two stereoisomers, the trans form 18α-glycyrrhetinic acid (AGA) and the cis form 18β-glycyrrhetinic acid (BGA) (18,19).…”

Section: Introductionmentioning

confidence: 99%

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Munirathinam

2011

Int J Oncol

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Abstract. Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as α and β stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anticancer activity. However, the effects and anticancer mechanism of α glycyrrhetinic acid in prostate cancer cells has not yet been evaluated. Therefore, we investigated the growth inhibition, induction of apoptosis and the anticancer mechanisms of 18α-glycyrrhetinic acid (AGA), on the androgen-independent metastatic prostate cancer cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells by inducing apoptosis as determined by Annexin V and flow cytometry analyses. Our studies also showed that HUVEC tube formation was drastically reduced when cultured in conditioned medium of AGA-treated DU-145 cells. In addition, AGA treatment prevented the invasion of DU-145 prostate cancer cells on matrigel coated transwells via down-regulation of NF-κB (p65), VEGF and MMP-9 expression. Furthermore, AGA treatment also downregulated the expression of pro-inflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8 in DU-145 cells. Interestingly, AGA simultaneously upregulated the expression of non-steroidal anti-inflammatory gene-1 (NAG-1) in DU-145 cells suggesting its anti-inflammatory activity on prostate cancer cells. Taken together, the results of this study suggest that AGA may be a promising anticancer agent that merits further investigation for the chemoprevention and treatment of prostate cancer.

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“…The results for compounds 6a-c, 7, 9-11, 13, and 15 are summarized in Table 3, and aciclovir 21) is also listed as a positive control. All compounds evaluated in this study showed no distinct inhibitory concentration (EC 50 ) values for antiviral activity less than the dose of 100 μM.…”

Section: Resultsmentioning

confidence: 99%

Molecular Symmetry and Biological Activities of New Symmetrical Tris(2-aminoethyl)amine Derivatives

Mibu

Yokomizo

Uchida

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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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)

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Anti-herpes Virus Type 1 Activity of Oleanane-Type Triterpenoids

Cited by 87 publications

References 11 publications

Synthesis and Biological Evaluation of Symmetrical 2,4,6-Trisubstituted 1,3,5-Triazine Derivatives

Synthesis and Biological Evaluation of Symmetrical 2,4,6-Trisubstituted 1,3,5-Triazine Derivatives

18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Molecular Symmetry and Biological Activities of New Symmetrical Tris(2-aminoethyl)amine Derivatives

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