• Proceedings of the PSK Conference
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• 2002.10a
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• pp.186-190
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• 2002

S- Adenosylhomocysteine hydrolase $(SAH)^1$ catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L-homocysteine. Inhibition of this enzyme accumulates S-adenosylhomocysteine, which in turn inhibits S-adenosyl-L-methionine dependent transmethylation, resulting in no formation of the capped methylated structure at the 5'-terminus of viral mRNA. Thus, S-adenosylhomocysteine hydrolase has been an attractive target for the development of broad spectrum of antiviral agents. (omitted)

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.2
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• pp.107-121
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• 2021

Skin hypopigmentation, which is observed in albinism or vitiligo, occurs when melanin synthesis is decreased by genetic, epigenetic, and other factors. To identify drug candidates that can promote melanin synthesis in cells, we screened an epigenetic modulator library consisting of 141 cell-permeable, small molecule drugs. B16/F10 murine melanoma cells were treated with each drug at 0.1 𝜇M and melanin synthesis and cell viability were subsequently monitored. As a result, (-)-neplanocin A, 3-deazaneplanocin A (DZNep), and DZNep hydrochloride were found to increase cellular melanin synthesis without causing cytotoxicity. Because these three structurally related drugs exhibited similar dose-dependent effects on melanin synthesis and cell viability, DZNep was selected as a representative drug for additional experiments. DZNep increased intracellular melanin content and tyrosinase (TYR) activity. DZNep also induced the expression of TYR, tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT) at the mRNA and protein levels. DZNep also induced the mRNA and protein expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanin synthesis. DZNep is a specific inhibitor of S-adenosylhomocysteine hydrolase and it caused the accumulation of S-adenosylhomocysteine that inhibits histone methyltransferases in cells. This study suggests that melanogenesis can be modulated by targeting S-adenosylhomocysteine hydrolase in certain cellular contexts.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.365.2-365.2
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• 2002

S-Adenosylhomocysteine hydrolase (SAH) catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L -homocysteine and has been an attractive target for the development of broad spectrum antiviral agents. Neplanocin A and 9-(dihydroxycyclopent-4' -enyl)adenine (DHCeA) have been known to inhibit SAH by cofactor (NAD＋) depletion mechanism and their inhibition is reversed by the addition of NAD＋ or dialysis. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.163.1-163.1
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• 2003

The inhibitory activities of various analogues of adenosine (Group I, Group II, Group III, Group IV, Group V) were assayed by using recombinant human placental SAH hydrolase. The activity of the SAH hydrolase was determined by measuring the formation of AdoHcy from Ado and Hcy. AdoHcy was analyzed by HPLC using C18 reverse-phase column. The peak of AdoHcy was monitored at 258 nm. Among the tested compounds, fluoroneplanocin A (LJ-276) was the most potent inhibitor.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.219.1-219.1
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• 2001

• Bulletin of the Korean Chemical Society
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• v.29 no.12
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• pp.2487-2490
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• 2008

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.245.3-246
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• 2003

S-Adenosylhomocysteine hydrolase (SAH) catalyzes the hydrolysis of S-adenosylhomocysteine to adenosine and L-homocysteine and has been an attractive target for the development of broad spectrum antiviral agents. Based on the potent inhibitory activity of neplanocin A against SAH, we have reported the synthesis and novel mechanism of action of fluoro-neplanocin A. (omitted)

• Biomedical Science Letters
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• v.12 no.2
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• pp.57-63
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• 2006

Deazaadenosine analogs such as 3-deazaadenosine (DZA), 3-deazaaristeromycin (DZAri) and ara-3-deazaadenine (DZAra-A) were developed as inhibitors of S-adenosylhomocysteine (Ado-Hcy) hydrolase (EC 3.3.1.1). These analogs were reported to induce apoptosis in human and murine leukemic cells. But, the mechanism involved in this apoptosis was not clarified yet. In the present study, we analyze the apoptosis induced by deazaadenosine analogs in human cervival cancer cell line, HeLa and the effect of Bcl-2 on this apoptosis. Whereas neither DZAri nor DZAra-A showed inhibitory effect on HeLa cell growth, DZA induced apoptosis in HeLa cells accompanied by cytochrome c release and activation of various caspases such as caspase-2,-8,-9 and -3. In HeLa-bcl-2 cell line, a stable transfectant of HeLa cell to overexpress Bcl-2, cytochrome c release, activation of all these caspases and the resulted apoptosis by DZA were completely prevented. By in vitro assay of cytochrome c release, in addition, DZA induced cytochrome c release from purified mitochondria of HeLa-pcDNA3 cells, but not HeLa-bcl-2 cells, even in the absence of cytosolic fraction. Therefore, it can be suggested that DZA might damage directly mitochondria leading to activate intrinsic pathway of caspase and thus induce apoptosis. DZA-induced apoptosis in HeLa cells may be in a bcl-2-inhibitable manner and irrelative of Ado-Hcy hydrolase.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.302-309
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• 2000

Based on (-)-neplanocin A with the 5'-hydroxyl substituted with fluoro, azido, or amino group, the corresponding xylo- and arabino derivatives were synthesized from D-ribose using the Mit-sunobu reaction as a key step. None of the final nucleosides did show either significant antiviral activities or cytotoxicities.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.241.1-241.1
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• 2003

Apio nucleosides whose 4'-hydroxymethyl group moves to 3'-position exhibit interesting biological activity such as antitumor or antiviral activity. On the other hand, neplanocin A and aristeromycin are the representative of the carbocyclic nucleosides and have been recognized as potent inhibitors of S-adenosylhomocysteine hydrolase. Based on these findings. it was of great interest to design apio analogues of neplanocin A and aristeromycin. (omitted)