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 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%.
Subject(s)
Animals , Carcinogenicity Tests , Cholanes/chemistry , Crystallography, X-Ray , Embryo, Mammalian/drug effects , Hydrogen Bonding , Models, Molecular , Molecular Conformation , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Potassium Channels/metabolism , Solvents , Teratogens/chemistry , Toxicity TestsABSTRACT
A través de los siglos, las sociedades han sentido temor por los efectos adversos que puede tener el entorno en el desarrollo del feto. Se conocen como teratógenos los agentes farmacológicos, químicos, físicos o infecciosos que actúan sobre el embrión o el feto ocasionando daño estructural o funcional. En este sentido, hemos hecho una revisión sobre los daños ocasionados al embrión y al feto por las drogas ilícitas a fin de ayudar a los pediatras en el reconocimiento de las anomalías producidas por ellas, entender el curso de dichos trastornos y así poder orientar al niño, a su familia y a la comunidad. Igualmente alertar a los adolescentes sobre el riesgo a que está sometida su descendencia en caso de consumirlas durante el embarazo . El efecto teratogénico de algunas de ellas es bien conocido como el de el alcohol y la cocaina, pero en otras está en estudio, de allí nuestro interés en investigar el posible efecto teratogénico u otros efectos de la marihuana, ácido lisérico (LSD), nicotina y cafeína, anfetaminas y solventes inorgánicos. Es de hacer notar que no se conoce ninguna estadística en nuestro país sobre esta problemática