• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한화장품학회지
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• 제47권2호
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• pp.107-121
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• 2021

백색증이나 백반증에서 관찰되는 피부 저색소침착은 유전적 요인, 후성유전적 요인 및 기타 요인에 의해 멜라닌 합성이 감소할 때 발생한다. 세포에서 멜라닌 합성을 촉진 할 수 있는 약물 후보를 확인하기 위해 141개의 세포 투과성 저분자 약물로 구성된 후성유전적 조절제 라이브러리를 스크리닝했다. B16/F10 쥐 흑색종 세포를 0.1 𝜇M에서 각 약물로 처리하고 멜라닌 합성 및 세포 생존력을 모니터링했다. 그 결과, (-)-네플라노신 A, 3-디아자네플라노신 A (DZNep) 및 DZNep 염산염이 세포 독성을 일으키지 않고 멜라닌 합성을 증가시키는 것으로 나타났다. 이 세 가지 구조적으로 관련된 약물은 세포 멜라닌 합성 및 세포 생존력에 유사한 용량 의존적 효과를 나타내었기 때문에 DZNep을 추가 실험을 위한 대표 약물로 선택하였다. DZNep는 세포내 멜라닌 함량과 티로시나제(TYR) 활성을 증가 시켰다. DZNep은 또한 mRNA와 단백질 수준에서 TYR, 티로시나제 관련 단백질 1 (TYRP1) 및 도파크롬 토토머라제 (DCT)의 발현을 유도했다. DZNep는 또한 멜라닌 합성의 주요 조절자인 소안구증 관련 전사 인자(MITF)의 mRNA와 단백질 발현을 유도했다. DZNep은 S-아데노실 호모시스테인 가수분해효소의 선택적 억제제이며 히스톤 메틸화효소를 저해하는 S-아데노실 호모시스테인의 세포내 축적을 유발하였다. 이 연구는 특정 세포 상황에서 S-아데노실 호모시스테인 가수분해효소를 표적함으로써 멜라닌 생성이 조절될 수 있음을 시사한다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.219.1-219.1
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• 2001

• Bulletin of the Korean Chemical Society
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• 제29권12호
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• pp.2487-2490
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• 2008

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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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)

• 대한의생명과학회지
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• 제12권2호
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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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• 제23권4호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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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)