Rossi M, Markovitz S, Callahan T
Carcinogenesis. 1987 Jul;8(7):881-7. doi: 10.1093/carcin/8.7.881.
The crystal and molecular structure of the cytochrome P-450 inhibitor, SKF-525A [2-(diethylamino)ethyl 2,2-diphenylpentenoate; proadifen hydrochloride] is described. Proadifen hydrochloride crystallized from an ethyl acetate and acetic acid mixture in the space group P2(1)/c with one molecule in the asymmetric unit. Cell constants are a = 18.716(4), b = 8.906(1), c = 14.201(3), beta = 109.41(1) degrees. The structure was solved using direct methods and was refined to an R value of 0.047; weighted R of 0.061 using 3757 reflections. From the crystal and molecular structure, it is seen that SKF-525A has two principal modes of complementary interactions with the enzyme available: polar and non-polar. Polar interactions that principally involve the chloride anion, the quaternary nitrogen atom and the carbonyl oxygen atom. In particular, there are two strong hydrogen bonds, one between Cl ... H-N, 3.090(1) A, the other between O2 ... H-C111 (one of the ethyl hydrogen atoms) at 3.411(2) A. The other is through non-polar interactions involving the phenyl and alkyl groups. Comparisons between proadifen hydrochloride and other inhibitors whose atomic coordinates are available reveal common features which correlate with their function. These include groups to provide necessary intermolecular contacts and bulk, such as a phenyl group and a hydrogen bond acceptor, as well as a tetrahedral atom, which allows for substrate flexibility.
描述了细胞色素P - 450抑制剂SKF - 525A [2 -（二乙氨基）乙基2,2 - 二苯基戊烯酸酯；盐酸普罗地芬]的晶体和分子结构。盐酸普罗地芬从乙酸乙酯和乙酸的混合物中结晶，空间群为P2(1)/c，不对称单元中有一个分子。晶胞常数为a = 18.716(4)，b = 8.906(1)，c = 14.201(3)，β = 109.41(1)°。该结构通过直接法解析，并精修至R值为0.047；使用3757个反射，加权R为0.061。从晶体和分子结构可以看出，SKF - 525A与该酶有两种主要的互补相互作用模式：极性和非极性。极性相互作用主要涉及氯离子阴离子、季氮原子和羰基氧原子。特别地，有两个强氢键，一个是Cl...H - N之间，键长为3.090(1) Å，另一个是O2...H - C111（乙基氢原子之一）之间，键长为3.411(2) Å。另一种是通过涉及苯基和烷基的非极性相互作用。盐酸普罗地芬与其他原子坐标已知的抑制剂之间的比较揭示了与其功能相关的共同特征。这些包括提供必要分子间接触和体积的基团，如苯基和氢键受体，以及一个四面体原子，它允许底物具有灵活性。
