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Title: Biological activity predictions, crystallographic comparison and hydrogen bonding analysis of cholane derivatives
Authors: Rajnikant
Chand, Bhavnaish
Keywords: Cholane;X-ray diffraction;Biological activity;Intra and intermolecular hydrogen bonds;Bifurcated hydrogen bonds;Solvent/solute interaction;Lipinski’s rule
Issue Date: Dec-2007
Publisher: CSIR
Abstract: 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 Pa (possibility of activity) and Pi (possibility of inactivity). Most of the probable activities have been characterized by Pa and Pi 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–θ and d–θ 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 96.5-99.3%.
Page(s): 458-469
ISSN: 0301-1208
Appears in Collections:IJBB Vol.44(6) [December 2007]

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