Chand Bhavnaish
Condensed Matter Physics Group, Post-Graduate Department of Physics, University of Jammu, Jammu Tawi-180006, India.
Indian J Biochem Biophys. 2007 Dec;44(6):458-69.
A total of eighteen molecules of cholane derivatives (I-XVIII) (a series of steroids) have been included to predict their pharmacological effects, specific mechanisms of action, known toxicities, drug-likeness, etc, by using the statistics of multilevel neighbourhoods of atoms (MNA) descriptors for active and inactive fragments. The biological activity spectra for substances have been correlated on SAR base (structure-activity relationships data and knowledge base), which provides the different P(a) (possibility of activity) and P(i) (possibility of inactivity). Most of the probable activities have been characterized by P(a) and P(i) values, which depict that all the molecules have high value of teratogen activity. The Lipinski's thumb rule predicts that all the cholane derivatives have stronger preponderance for "cancer-like-drug" molecules and some of their related analogous have entered in the ANCI (American National Cancer Institute) database. Some selected bond distances and bond angles of interest have been taken into account and deviation of bond distances/bond angles, vis-a-vis the substitutional group and X-H...A intra/intermolecular hydrogen bonds has been discussed in detail. X-H...A intra and intermolecular hydrogen bonds in the molecules have been described with the standard distance and angle cut-off criteria. D-theta and d-theta. scatter plots for intra- and intermolecular interactions are presented for better understanding of packing interactions existing among these derivatives. There exists only one C-H...O intramolecular bifurcated hydrogen bond. while high tendency of intermolecular bifurcated hydrogen bonds based on a defined O-H...O has been observed, in which O atom acts as a prototype donor as well as acceptor. The frequency of occurrence of C-H...O hydrogen bonds is predominant (i.e. 85.7%) in intramolecular interactions, whereas in intermolecular interactions, frequency of occurrence for O-H...O interactions is 62.9%. Solvent-solute/solute-solvent interactions have also been investigated to understand more complicated processes that occur for biomolecules in aqueous solutions. The number of hydrogen donors in each derivative is less than 5, except for molecule XVIII and which has 91.3% of drug-likeness, instead of observed range of 96.5-99.39%.
总共纳入了18种胆烷衍生物（I - XVIII）（一系列甾体），通过使用活性和非活性片段的原子多级邻域（MNA）描述符统计数据，来预测它们的药理作用、具体作用机制、已知毒性、类药性等。物质的生物活性谱已基于构效关系（SAR）库（结构 - 活性关系数据和知识库）进行关联，该库提供了不同的P(a)（活性可能性）和P(i)（非活性可能性）。大多数可能的活性已通过P(a)和P(i)值进行表征，这些值表明所有分子都具有高致畸活性值。Lipinski经验法则预测，所有胆烷衍生物对“类癌药物”分子具有更强的优势，并且它们的一些相关类似物已进入美国国立癌症研究所（ANCI）数据库。考虑了一些选定的感兴趣的键距和键角，并详细讨论了键距/键角相对于取代基和X - H...A分子内/分子间氢键的偏差。分子中的X - H...A分子内和分子间氢键已根据标准距离和角度截止标准进行描述。给出了分子内和分子间相互作用的D - theta和d - theta散点图，以便更好地理解这些衍生物之间存在的堆积相互作用。仅存在一个C - H...O分子内分叉氢键，而基于定义的O - H...O观察到分子间分叉氢键的高趋势，其中O原子既作为原型供体又作为受体。C - H...O氢键在分子内相互作用中的出现频率占主导（即85.7%），而在分子间相互作用中，O - H...O相互作用的出现频率为62.9%。还研究了溶剂 - 溶质/溶质 - 溶剂相互作用，以了解生物分子在水溶液中发生的更复杂过程。除了分子XVIII外，每种衍生物中的氢供体数量均小于5，分子XVIII具有91.3%的类药性，而观察到的范围为96.5 - 99.39%。
