Withasteroid 화합물들에 있어 Ecdysone 관련작용과 화학구조특성 = Relationship between Chemicostructural Properties and Ecdysone-Related Activity in Withasteroids

국문 초록 (Abstract)

본 연구는 withasteroid 구조유사물질들의 물리화학적 특성과 엑다이손 활성과의 상관성을 규명하고자 수행되었다. 이를 위해 선정된 스테로이드 화합물들은 그들의 엑다이손 관련 활성과 스테로이드 종에 따라 4군으로 분류되었으며 각 화합물들에 대해 log P를 비롯한 주요 물리화학적 및 분자구조 변수들과 분자내 전하분포가 컴퓨터 프로그램을 사용하여 산출/도시되어 그 결과들이 엑다이손 활성과 관련하여 면밀히 비교, 분석되었다. Withasteroid 구조유사물질 중 유일하게 엑다이손 작용물질인 withaperuvin D는 엑다이손 활성을 갖는 ecdysteroid 구조유사물질들 및 hexanorcucurbitacin D와 동일하게 엑다이손 관련 작용을 갖고 있지 않은 다른 withasteroid 구조유사물질들에 비해 현저히 낮은 log p 값을 나타내었다. 또한 이들 Withaperuvin D, ecdysteroid 구조유사물질들 및 hexanorcucurbitacin D는 엑다이손 관련 작용을 갖고 있지 않은 다른 withasteroid 구조유사물질들에 비해 전체적으로 더 높은 수소 결합능을 가지고 있으며 withaperuvin D는 다른 withasteroid 구조유사물질들과 비교하여 스테로이드 기본 구조상에서 특히 첫 번째 고리부분을 중심으로 엑다이스테로이드 구조유사물질들 및 hexanorcucurbitacin D과 유사한 분자 전하분포 형태를 나타내었다. 이러한 결과들은 스테로이드 화합물들에 있어서는 log P, 수소 결합능, 분자내 전하분포와 같은 물리화학적 특성들이 생체내 수용체의 배위자와 생체 수용체 단백질사이의 결합활성도에 복합적으로 영향을 미칠 수 있음을 제시한다.

다국어 초록 (Multilingual Abstract)

The specific correlation between chemicostructural properties and ecdysone-related activity in withasteroid analogues was investigated. Examples of steroidal compounds selected to be compared were classified into 4 groups according to their ecdysone-related activity and chemical species and molecular physicochemical parameters values such as log P, hydrophilic-lipophilic balance(H.L.B.), solubility parameter(S.P.), hydrophilic surface(H.P.S.), hydrogen bond(H.B.), dipole moment(D.M.), connectivity 1 and Kappa 2 and distribution of electronic charge were calculated/drawn using computer program to be compared among groups. Withaperuvin D, a ecdysteroid agonist, markedly showed the lower Log P level than other withasteroid analogues without ecdysone-related activity, as other examined steroidal ecdysone agonists such as 20OH-ecdysone and hexanorcucurbitacin D did. Withaperuvin D and other examined ecdysteroid agonists overally showed the higher H.B. level than withasteroids without ecdysone-related activity. Also, Withaperuvin D showed the significantly different pattern of the molecular electron charge distribution, especially in the first ring of the basic steroidal structure, compared to withsteroids without ecdysone-related activity. It`s pattern of the molecular electron charge distribution in the first ring was similar to those of other examined steroidal ecdysone agonists such as 20 OH-ecdysone and hexanocucurbitacin. These results suggest that, in steroids, physicochemical properties such as log P, hydrogen bonding, and molecular electron charge distribution may combinedly affect the binding ability of ligands with receptors to result in the ecdysteroidal activity.

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