Molecular modeling study of tubulosine and other related ipecac alkaloids.

A molecular modeling study of two alkaloids, tubulosine and psychotrine, isolated from the sap of Pogonopus speciosus, and other related ipecac alkaloids, showed that these flexible alkaloids favor a nonplanar structure. The biologically active compounds had conformations with a similar angle between aromatic ring A, the nitrogen in ring B, and ring D. This angle was related to the biological activity reported for these compounds. Our results support the hypothesis of two different types of receptor interactions, one for the nonplanar compounds and another for the planar compounds.

[Molecular modeling of N-isopropyl lisergamides analogous to LSD using molecular mechanics and quantum mechanical calculations]. / Modelado molecular de N-isopropil lisergamidas analogas al LSD, utilizando cálculos de mecánica molecular y mecánica cuántica.

Molecular mechanics and quantum mechanics were used to study the preferred conformations, electron densities and frontier orbitals of d-LSD and their analogs with the isopropyl amide group, compounds with reported activity over the serotonin receptor. Electron densities and frontier orbitals for isopropyl analogs were similar to d-LSD, so these properties can not be related with the changes in biological activity previously reported. It was found that isopropyl analogs have preferred conformations similar to d-LSD with small variation in the alkylamide group. The variation in the alkylamide group causes small variations in the orientation of the carbonyl amide group, our study suggests that this variation could affect the binding with the hydrophobic region of the receptor.

Compounds that inhibit chymotrypsin and cell replication.

Several compounds have been tested for their ability to inhibit bovine pancreatic alpha-chymotrypsin (Ki) and their ability to inhibit cell replication (IC50). There is good agreement over three orders of magnitude between the Ki and the IC50 values of these compounds. The data support the hypothesis that a cellular, chymotrypsin-like activity is necessary for cell replication.