JP2010180155A - Novel acetylene alcohol derivative, ngf-related active substance and process for producing the same - Google Patents
Novel acetylene alcohol derivative, ngf-related active substance and process for producing the same Download PDFInfo
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- -1 acetylene alcohol derivative Chemical class 0.000 title claims abstract description 28
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 239000013543 active substance Substances 0.000 title claims description 15
- 238000000034 method Methods 0.000 title description 9
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- 241000243142 Porifera Species 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
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- 241000972644 Petrosia Species 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 18
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- 150000002430 hydrocarbons Chemical group 0.000 abstract 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 28
- 102000015336 Nerve Growth Factor Human genes 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 210000004027 cell Anatomy 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 14
- 230000014511 neuron projection development Effects 0.000 description 10
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- XHUCVXPLRGMGKS-YQYMCEQDSA-N (z,6r,7r,8s)-24-methylpentacos-16-en-2,4-diyne-1,6,7,8-tetrol Chemical compound CC(C)CCCCCC\C=C/CCCCCCC[C@H](O)[C@@H](O)[C@H](O)C#CC#CCO XHUCVXPLRGMGKS-YQYMCEQDSA-N 0.000 description 5
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
本発明は、海綿（学名：Ｐｅｔｒｏｓｉａ ｓｔｒｏｎｇｙｌａｔａ）などから単離可能な新規アセチレンアルコール誘導体、ＮＧＦ関連活性物質及びその製造方法に関する。 The present invention relates to a novel acetylene alcohol derivative, an NGF-related active substance, and a method for producing the same, which can be isolated from sponges (scientific name: Petrosia stronglata).
琉球列島は、世界で最も生物多様性の高い熱帯海洋生物地理区であるインド−西太平洋域に属しており、サンゴ礁を形成するサンゴをはじめ多様な海洋生物が棲息している。例えば沖縄本島に投置されている構造物のポール一本から海綿だけでも４０種類以上が採取された例がある。このことは琉球列島が非常に多様性に富んだ海域であることの裏付けになるものである。こうした海の恵みを生かす研究が盛んに行われている。 The Ryukyu archipelago belongs to the Indo-West Pacific region, which is the world's most biodiversity tropical marine biogeographic area, and is home to a variety of marine life, including corals that form coral reefs. For example, there is an example in which more than 40 types of sponges are collected from a single pole of a structure placed on the main island of Okinawa. This confirms that the Ryukyu Islands is a very diverse sea area. There is a lot of research that takes advantage of the bounty of the sea.
例えば、沖縄産のオニヒトデから抽出されたＮＧＦ活性をもつステロイド配糖体が報告されている（特許文献１）。 For example, a steroidal glycoside having NGF activity extracted from Okinawan starfish has been reported (Patent Document 1).
以上のように、沖縄の海洋生物には有用な作用をもつものが多くあることが予測される。 As described above, it is predicted that many marine organisms in Okinawa have useful effects.
そこで、本発明者らは沖縄の海洋生物数百検体についてＮＧＦ活性の有無を精査した。その結果、高い活性をもつ化合物を発見したので、ここに報告する。 Therefore, the present inventors closely examined the presence or absence of NGF activity in hundreds of Okinawan marine organisms. As a result, we found a compound with high activity, and we will report it here.
すなわち、本発明は、沖縄の海洋生物についての研究を通じて明らかになった新規アセチレンアルコール誘導体及び新規ＮＧＦ関連活性物質並びにその製造方法を提供する。 That is, the present invention provides a novel acetylene alcohol derivative, a novel NGF-related active substance, and a method for producing the same, which have been clarified through research on Okinawan marine organisms.
海綿からはいくつかの神経栄養因子（ＮＧＦ関連活性物質）が抽出されている（非特許文献１、２）。本発明者らはそれらに報告のない新規アセチレンアルコール誘導体を見いだしたと共に、それら新規アセチレンアルコール誘導体がＮＧＦ様神経突起伸長活性を示すことを発見した。更に、ＮＧＦに対してその作用を増強する場合（以下、「ＮＧＦ増強活性」と称する）もあることを発見した（本明細書において、ＮＧＦ様神経突起伸長活性とＮＧＦ増強活性とを併せて「ＮＧＦ関連活性」と称し、ＮＧＦ関連活性をもつ化合物を併せて「ＮＧＦ関連活性物質」と称する）。そしてこれらの知見に基づき以下の発明を完成した。
Several neurotrophic factors (NGF-related active substances) have been extracted from sponges (
請求項１に係るアセチレンアルコール誘導体は、下記一般式（１）で表されるものである。
The acetylene alcohol derivative according to
（式（１）中、ＸはＯＨ、ＯＲ３、Ｈ、Ｒ３から選択される（Ｒ３は炭素数１〜５の炭化水素基から選択される）。；Ｒ１はＨ、炭素数１〜５の炭化水素基から選択される。；Ｒ２は炭素数５〜３０の炭化水素基から選択される。；ｎは自然数）
請求項２に係るアセチレンアルコール誘導体は、請求項１において、前記一般式（１）中のＸがＯＨ基であり、Ｒ１がＨ、ｎが３、Ｒ２が下記（Ａ）〜（Ｃ）の置換基のうちの何れか１つ（式中の＊の部分にて炭素原子に結合する）であるものである。
(In the formula (1), X is selected from OH, OR 3 , H, and R 3 (R 3 is selected from a hydrocarbon group having 1 to 5 carbon atoms); R 1 is H and has 1 carbon atom. Selected from hydrocarbon groups having ˜5; R 2 is selected from hydrocarbon groups having 5 to 30 carbon atoms; n is a natural number)
The acetylene alcohol derivative according to
請求項３に係るＮＧＦ関連活性物質は、請求項１又は２に記載のアセチレンアルコール誘導体を含むことを特徴とする。
An NGF-related active substance according to
請求項４に係るＮＧＦ関連活性物質は、請求項３において、尋常海綿綱に属する海洋生物からの抽出液であることを特徴とする。
The NGF-related active substance according to
請求項５に係るアセチレンアルコール誘導体の製造方法の特徴は、請求項１又は２に記載のアセチレンアルコール誘導体を海綿（学名：Ｐｅｔｒｏｓｉａ ｓｔｒｏｎｇｙｌａｔａ、以下「沖縄産海綿Ａ」と称する）から抽出分離する工程を有することにある。
A feature of the method for producing an acetylene alcohol derivative according to
本発明のＮＧＦ関連活性物質は高い活性を有する従来にない化合物である。そして、化学構造が比較的単純なため、容易な全合成が期待できる。 The NGF-related active substance of the present invention is an unprecedented compound having high activity. And since the chemical structure is relatively simple, an easy total synthesis can be expected.
（新規アセチレンアルコール誘導体）
本発明の新規アセチレンアルコール誘導体は上記一般式（１）にて表される化合物である。式（１）中におけるＸはＯＨ又はＯＭｅ、特にＯＨであることが望ましい。
(New acetylene alcohol derivative)
The novel acetylene alcohol derivative of the present invention is a compound represented by the above general formula (1). X in the formula (1) is preferably OH or OMe, particularly OH.
Ｒ１はＨ又はＭｅ、特にＨであることが望ましい。ｎは下限として１、２、３が例示でき、上限として１０、８、６、４、３が例示でき、これら下限と上限とは任意に組み合わせることができる。特に１〜４程度が望ましく、１〜３がより望ましく、２又は３が更に望ましい。 R 1 is preferably H or Me, especially H. n can be exemplified by 1, 2, and 3 as the lower limit, and can be exemplified by 10, 8, 6, 4, and 3 as the upper limit, and these lower and upper limits can be arbitrarily combined. Especially about 1-4 is desirable, 1-3 is more desirable, and 2 or 3 is still more desirable.
Ｒ２の炭素数は５〜２５であることが望ましく、１０〜２０であることが更に望ましい。Ｒ２は飽和炭化水素基であっても不飽和炭化水素基であってもよい。不飽和炭化水素基である場合には４位に二重結合をもつものが挙げられる。また、三重結合をもつこともできる。三重結合は末端にもつことができる。更に、Ｒ２は直鎖状の炭化水素基であっても分枝した炭化水素基であっても良い。Ｒ２としては上述したの置換基［（Ａ）：４−ヘプタデカニル基、（Ｂ）：１６−メチル−４−ヘプタデカニル基、（Ｃ）：４，２０−トリコサジエン−２２−イニル基］が挙げられる。特に（Ａ）又は（Ｂ）の置換基が望ましく、（Ａ）の置換が更に望ましい。 R 2 preferably has 5 to 25 carbon atoms, more preferably 10 to 20 carbon atoms. R 2 may be a saturated hydrocarbon group or an unsaturated hydrocarbon group. In the case of an unsaturated hydrocarbon group, one having a double bond at the 4-position may be mentioned. It can also have a triple bond. Triple bonds can be at the ends. Further, R 2 may be a linear hydrocarbon group or a branched hydrocarbon group. Examples of R 2 include the substituents described above [(A): 4-heptadecanyl group, (B): 16-methyl-4-heptadecanyl group, (C): 4,20-tricosadiene-22-ynyl group]. . In particular, the substituent of (A) or (B) is desirable, and the substitution of (A) is more desirable.
特に望ましいアセチレンアルコール誘導体を以下に示す（化合物（２）〜（４））。これら化合物はＸがＯＨ、Ｒ１がＨ、ｎが３である。Ｒ２については化合物（２）が置換基（Ａ）に、化合物（３）が置換基（Ｂ）に、化合物（４）が置換基（Ｃ）に対応している。 Particularly desirable acetylene alcohol derivatives are shown below (compounds (2) to (4)). In these compounds, X is OH, R 1 is H, and n is 3. For R 2 , compound (2) corresponds to substituent (A), compound (3) corresponds to substituent (B), and compound (4) corresponds to substituent (C).
本発明の新規アセチレンアルコール誘導体を得る方法としては特に限定されず、公知の方法を組み合わせて合成する方法が採用できる。また、海洋生物から抽出する方法も採用できる。海洋生物としては海綿が例示できる。海綿としては、分類学上、尋常海綿綱に含まれるものが例示できる。特に沖縄の海洋にて産する海綿（学名：Ｐｅｔｒｏｓｉａ ｓｔｒｏｎｇｙｌａｔａ）から大量に抽出することが可能である。沖縄産海綿Ａは石垣島周辺海域に非常に多く生息しており、オーバーハング裏面など少し暗い環境を好む種である。生息量も非常に多く、抽出の為に量が必要になった場合にも容易に確保できる。 The method for obtaining the novel acetylene alcohol derivative of the present invention is not particularly limited, and a method of synthesizing by combining known methods can be employed. Moreover, the method extracted from a marine organism is also employable. Examples of marine organisms include sponges. Examples of the sponge include those included in the common sponge class in terms of taxonomy. In particular, it is possible to extract a large amount from sponges (scientific name: Petrosia stronglata) produced in the Okinawa ocean. Okinawan sponge A is inhabited in the sea around Ishigaki Island, and is a species that prefers a slightly dark environment such as the back of the overhang. The abundance is very large, and it can be easily secured even if the amount is needed for extraction.
海洋生物からの抽出方法としては特に限定されない。海洋生物を粉砕したりすりつぶしたりした後、有機溶媒、水などに浸漬し、抽出を行うことができる。抽出液はろ過などを行って夾雑物を除くことが望ましい。その後、適正な担体及び溶媒を用いて分画を行うことができる。海洋生物はそのまま、凍結状態、乾燥状態などどのような状態で抽出操作に供しても良い。
（ＮＧＦ関連活性物質）
本発明のＮＧＦ関連活性物質としては前欄にて説明した一般式（１）で表される新規アセチレンアルコール誘導体から任意に選択できる。特に式（２）〜（４）の化合物の何れかであることが望ましい。特に、一般式（２）の化合物が望ましい。
The extraction method from marine organisms is not particularly limited. After pulverizing or crushing marine organisms, it can be extracted by immersion in an organic solvent, water, or the like. It is desirable to remove impurities by filtering the extract. Thereafter, fractionation can be performed using an appropriate carrier and solvent. The marine organisms may be subjected to the extraction operation in any state such as a frozen state or a dried state.
(NGF-related active substance)
The NGF-related active substance of the present invention can be arbitrarily selected from the novel acetylene alcohol derivatives represented by the general formula (1) described in the previous column. In particular, any one of the compounds of formulas (2) to (4) is desirable. In particular, the compound of the general formula (2) is desirable.
更に、尋常海綿綱に属する海洋生物からの抽出液を混合物である場合も含め、そのまま採用することもできる。例えば、式（２）〜（４）の化合物は海洋生物中から抽出することができる。海洋生物からの抽出方法としては新規アセチレンアルコール誘導体と同様の方法（抽出、分画などを組み合わせた分離方法）が採用できるため、更なる説明は省略する。抽出液がＮＧＦ関連活性物質であるか否かの判断は得られた分離物中のＮＧＦ関連活性の強度及び毒性の強度を判定することで行うことができる。ＮＧＦ関連活性の測定は、ＰＣ１２細胞など一般的な細胞を用いた試験系を用い、神経突起伸長を誘導するかどうかで判断する。単独で神経突起伸長を誘導する場合にはＮＧＦ様神経突起伸長活性を示す分画であり、ＮＧＦの活性を増強する場合にはＮＧＦ増強活性を示す分画である。ＰＣ１２細胞が損傷を受ける場合には毒性があるものと判断できる。 Furthermore, an extract from marine organisms belonging to the common sponge class can be used as it is, including when it is a mixture. For example, the compounds of formulas (2) to (4) can be extracted from marine organisms. As a method for extraction from marine organisms, a method similar to that for a novel acetylene alcohol derivative (a separation method combining extraction, fractionation, etc.) can be adopted, and further explanation is omitted. Whether or not the extract is an NGF-related active substance can be determined by determining the intensity of NGF-related activity and the intensity of toxicity in the obtained isolate. NGF-related activity is measured by determining whether neurite outgrowth is induced using a test system using general cells such as PC12 cells. When neurite outgrowth is induced alone, it is a fraction showing NGF-like neurite outgrowth activity, and when enhancing NGF activity, it is a fraction showing NGF enhancing activity. If PC12 cells are damaged, it can be determined that they are toxic.
〔試験１：沖縄産海綿ＡからＮＧＦ関連活性物質を分離する方法〕
（抽出）
湿質量３８０ｇの沖縄産海綿Ａ（Ｐｅｔｒｏｓｉａ ｓｔｒｏｎｇｙｌａｔａ）から抽出した酢酸エチル層エキス１．６ ｇをシリカゲルカラムクロマトグラフィー［Ｈｉ−ＦｌａｓｈＴＭ ２Ｌ （４５ｇ），クロロホルム：メタノール＝１００：０〜９０：１０（４０分間， ｌｉｎｅａｒ ｇｒａｄｉｅｎｔ）， 流速１０ｍＬ／分］によって１０画分に分離した（Ｆｒ．１〜１０）。次にＦｒ．８（６２．２ ｍｇ，３５〜４０分）を高速液体クロマトグラフィー ［Ｄｅｖｅｌｏｓｉｌ ＯＤＳ−ＵＧ−５ （１０×２５０ｍｍ），９０％メタノール， 流速５ｍＬ／分，検出ＵＶ波長２４５ｎｍ］によって７画分に分離した （Ｆｒ．８−１〜７）。Ｆｒ．８−３（５．０ ｍｇ， １１〜１２分）は純粋であったため、Ｐｅｔｒｏｓｉｏｌ Ａ（化合物（２）に相当）と名づけた。Ｆｒ．８−５（４．３ｍｇ，１３〜１３．５分）は精製不十分であったためさらに高速液体クロマトグラフィー ［Ｄｅｖｅｌｏｓｉｌ ＯＤＳ−ＵＧ−５ （１０×２５０ｍｍ），９０％メタノール，流速４ｍＬ／分，検出ＵＶ波長２４５ｎｍ］で精製し、４画分を得た（Ｆｒ．８−５−１〜４）。Ｆｒ．８−５−２（３．７ｍｇ，１６〜１８分）は純粋であったため、Ｐｅｔｒｏｓｉｏｌ Ｂ（化合物（３）に相当）と名づけた。Ｆｒ．８−５−３（０．４ｍｇ，１８〜１９分）もまた純粋であったのでＰｅｔｒｏｓｉｏｌ Ｃ（化合物（４）に相当）と名づけた。またＦｒ．８−６（１０．６ｍｇ，１３．５〜１６．５分）も精製不十分であったので高速液体クロマトグラフィー ［Ｄｅｖｅｌｏｓｉｌ ＯＤＳ−ＵＧ−５ （１０×２５０ｍｍ），９０％メタノール，流速４ｍＬ／分，検出ＵＶ波長２４５ｎｍ］によって精製し、４画分を得た（Ｆｒ．８−６−１〜４）。Ｆｒ．８−６−２（１．２ ｍｇ，１５〜１６分）は純粋なＰｅｔｒｏｓｉｏｌ Ｂ、Ｆｒ．８−６−３（９．０ ｍｇ，１６〜１９分）は純粋なＰｅｔｒｏｓｉｏｌ Ｃであった（図１）。
・Ｐｅｔｒｏｓｉｏｌ Ａの物理化学的諸性質
外観：淡茶色粉末、分子式：Ｃ２５Ｈ４２Ｏ４、ＭＳ（ＥＳＩ＋）：ｍ／ｚ ４２９．２９８６ ［Ｍ＋Ｎａ］＋ （＋１．０ ｍＤａ）、［α］２５ Ｄ：−２．９（ｃ０．１６）、ＵＶ（ＭｅＯＨ）：λｍａｘ ２０３（ε１７００）、２３１（ε４３０）、２４３（ε３８０）、２５７（ε２５０）ｎｍ、ＩＲ：３３６３（ｂｒ）、３００５、１１１４、１０７１、１０３１、６８０ｃｍ−１。ＮＭＲデータ（ＣＤＣｌ３：ＣＤ３ＯＤ＝４：１。以下同じ）を表１に示す。
・Ｐｅｔｒｏｓｉｏｌ Ｂの物理化学的諸性質
外観：白色粉末、分子式：Ｃ２６Ｈ４４Ｏ４、ＭＳ（ＥＳＩ＋）：ｍ／ｚ４４３．３１４２［Ｍ＋Ｎａ］＋（＋１．０ｍＤａ）、［α］２７ Ｄ−３．０（ｃ０．２５）、ＵＶ（ＭｅＯＨ）：λｍａｘ２０５（ε１３００）， ２３０（ε６２０）， ２４３（ε４８０）， ２５７（ε３００）ｎｍ、ＩＲ：３３５６（ｂｒ），３００５，１１１４，１０７１，１０３１ｃｍ−１。ＮＭＲデータを表１に示す。
・Ｐｅｔｒｏｓｉｏｌ Ｃの物理化学的諸性質
外観：白色粉末、分子式：Ｃ３１Ｈ４８Ｏ４、ＭＳ（ＥＳＩ＋）：ｍ／ｚ４８５．３６４３［Ｍ＋Ｈ］＋（＋１．７ｍＤａ），５０７．３４６１ ［Ｍ＋Ｎａ］＋（＋１．６ｍＤａ）、［α］２６ Ｄ：−３．６（ｃ０．１３）、ＵＶ（ＭｅＯＨ）：λｍａｘ２２２（ε８６００）ｎｍ、ＩＲ：３３６０（ｂｒ），３３１３，１１１４，１０７１，１０３２，６８０ｃｍ−１。ＮＭＲデータを表１に示す。
[Test 1: Method for separating NGF-related active substance from Okinawan sponge A]
(Extraction)
1.6 g of ethyl acetate layer extract extracted from Okinawa sponge A (petrosia stronglata) with a wet mass of 380 g was subjected to silica gel column chromatography [Hi-
Physicochemical properties of Petrosiol A Appearance: light brown powder, molecular formula: C 25 H 42 O 4 , MS (ESI +): m / z 429.2986 [M + Na] + (+1.0 mDa), [α] 25 D : -2.9 (c0.16), UV (MeOH): λ max 203 (ε1700), 231 (ε430), 243 (ε380), 257 (ε250) nm, IR: 3363 (br), 3005, 1114 , 1071, 1031, 680 cm −1 . NMR data (CDCl 3 : CD 3 OD = 4: 1, the same applies hereinafter) is shown in Table 1.
Physicochemical properties of Petrosiol B Appearance: white powder, molecular formula: C 26 H 44 O 4 , MS (ESI +): m / z 443.3142 [M + Na] + (+1.0 mDa), [α] 27 D −3 0.0 (c 0.25), UV (MeOH): λ max 205 (ε1300), 230 (ε620), 243 (ε480), 257 (ε300) nm, IR: 3356 (br), 3005, 1114, 1071, 1031 cm -1 . NMR data is shown in Table 1.
Physicochemical properties of Petrosiol C Appearance: white powder, molecular formula: C 31 H 48 O 4 , MS (ESI +): m / z 485.3364 [M + H] + (+1.7 mDa), 507.3461 [M + Na] + (+1.6 mDa), [α] 26 D : -3.6 (c0.13), UV (MeOH): λ max 222 (ε8600) nm, IR: 3360 (br), 3313, 1114, 1071, 1032 680 cm- 1 . NMR data is shown in Table 1.
〔試験２：ＮＧＦ関連活性物質の活性評価〕
ラット副腎髄質褐色細胞腫由来ＰＣ１２細胞は、理研セルバンクから入手した。
[Test 2: Activity evaluation of NGF-related active substances]
Rat adrenal medullary pheochromocytoma-derived PC12 cells were obtained from RIKEN Cell Bank.
凍結保存細胞（２ｘ１０4細胞）を培地（ＭＥＭＥ−１０％牛胎児血清−５％馬血清）で洗浄し、培地１０ｍＬとともに９ｃｍシャーレに撒き、５％ＣＯ2雰囲気下、３７℃、１週間静置培養した。細胞を収穫し新しい培地で２ｘ１０5細胞／シャーレになるように希釈して１週間培養する継代培養操作を４回以上繰返した後、収穫した細胞を試験に用いた（継代操作は１２回まで）。以下、培養とは５％ＣＯ2雰囲気下、３７℃で行うものとする。 Cryopreserved cells (2 × 10 4 cells) were washed with a medium (MEME-10% fetal calf serum-5% horse serum), spread in a 9 cm petri dish together with 10 mL of medium, and left at 37 ° C. for 1 week in a 5% CO 2 atmosphere. Cultured. The subculture was repeated 4 times or more after the cells were harvested, diluted to 2 × 10 5 cells / dish with a new medium and cultured for 1 week, and then the harvested cells were used for the test (the subculture was performed 12 times). Until). Hereinafter, culturing is performed at 37 ° C. in a 5% CO 2 atmosphere.
２４穴マイクロプレートの各ウエルに、２ｘ１０4細胞のＰＣ１２細胞を含む培地１ｍＬを入れ、ＣＯ２インキュベータ中、３７℃で２４時間静置培養した。培地を、適当な濃度のサンプルを含む無血清ＭＥＭＥ培地１ｍＬ（１％ＤＭＳＯ含有）に交換し、２４時間ごとに１週間、細胞の様子を観察した。計約１００細胞が観察できる視野３つを無作為に選択し、突起長が細胞の長径より長い細胞数を計測して、その割合をパーセントに換算して、神経突起伸張率（％）とした。各濃度について３回ずつ測定した。結果を表２、図２（経時変化）及び図３（６日後の神経突起伸張率）に示す。何も加えない（０μＭ）場合には神経突起伸張率は０であり、ＮＧＦを４０ｎｇ／ｍＬ添加した場合には６日後に７４．３％であった。 1 mL of a medium containing 2 × 10 4 cells of PC12 cells was placed in each well of a 24-well microplate, and statically cultured at 37 ° C. for 24 hours in a CO 2 incubator. The medium was replaced with 1 mL of serum-free MEME medium (containing 1% DMSO) containing a sample with an appropriate concentration, and the state of the cells was observed every 24 hours for 1 week. Three fields of view in which about 100 cells in total can be observed were randomly selected, the number of cells whose projection length was longer than the major axis of the cell was counted, and the ratio was converted to percentage to obtain the neurite extension rate (%). . Three measurements were taken for each concentration. The results are shown in Table 2, FIG. 2 (change over time) and FIG. 3 (neurite outgrowth after 6 days). When nothing was added (0 μM), the neurite outgrowth rate was 0, and when NGF was added at 40 ng / mL, it was 74.3% after 6 days.
表２、図２及び３から明らかなように、Ｐｅｔｒｏｓｉｏｌ Ａ〜Ｃすべてにおいて神経突起伸張活性が存在することが分かった。その中でもＰｅｔｒｏｓｉｏｌ Ａ及びＰｅｔｒｏｓｉｏｌ ＢがＰｅｔｒｏｓｉｏｌ Ｃよりも神経突起伸張率が高いことが分かった。Ｐｅｔｒｏｓｉｏｌ ＡとＢとではＰｅｔｒｏｓｉｏｌ Ａの方が僅かに高い神経突起伸張率を示した。 As is clear from Table 2 and FIGS. 2 and 3, it was found that there was neurite outgrowth activity in all Petrosiols AC. Among them, it was found that Petrosiol A and Petrosiol B had a higher neurite outgrowth rate than Petrosiol C. Petrosiol A and B showed slightly higher neurite outgrowth in Petrosiol A.
本発明の新規アセチレンアルコール誘導体はＮＧＦ関連活性などの発現が期待できる。ＮＧＦ関連活性を有する物質は薬理作用として痴呆治療、学習能力向上などに有効な作用を発揮することが期待され、薬剤としての応用が期待できる。 The novel acetylene alcohol derivative of the present invention can be expected to express NGF-related activity. A substance having NGF-related activity is expected to exert an effective action as a pharmacological action for treating dementia, improving learning ability, and the like, and can be expected to be applied as a drug.
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| CN115381800A (en) * | 2022-07-05 | 2022-11-25 | 中国科学院生态环境研究中心 | Selective agonist for liver X receptor and application |
| CN115381800B (en) * | 2022-07-05 | 2023-08-25 | 中国科学院生态环境研究中心 | Selective agonist of liver X receptor and application thereof |
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