Biological activity of an antibiotic puromycin—A theoretical study.

Puromycin is known to be an anti-tumor agent. Evaluation of interaction energy of this molecule with nucleic acid bases and base pairs has been performed using quantum-mechanical perturbation technique. Both in-plane and stacking energies have been evaluated. These energy values along with their sites of association have been compared with the standard values during transcription process. The results have been examined in the light of their biological significance.

A theoretical study of acriflavin-DNA binding.

A theoretical study of binding behaviour of acriflavin, a well-known mutagen, with DNA base pairs such as AT, GC, TA and CG has been performed using CNDO/2 method to compute net atomic charges and dipoles located at various centres in acriflavine as well as base pairs. Acriflavine-DNA base pair interactions have been evaluated using second order perturbation method with multicentered multipole approximation. Only minimum energy configurations have been reported. Results have been discussed with a view to obtain a comparative behaviour of other similar dyes like proflavine and acridine orange.

Stacking interactions between demethylated ellipticines and DNA base pairs--a quantum mechanical study.

A study of the binding behaviour of ellipticine compounds, derivatives of pyrido (4-3b) carbazole, has been carried out to elucidate the relationship between the drug-activity and demethylation of ellipticine. An all valence electron method (CNDO/2) has been employed to compute molecular charge distribution corresponding to various atomic centres of ellipticines and DNA base pairs. Using these atomic charges and dipoles, intermolecular interaction energy has been calculated with the help of second order perturbation theory and multicentered-multipole expansion technique. A comparative analysis of the binding patterns for nor-5,11-dimethyl-ellipticine and nor-11-methyl-ellipticine has been presented vis-a-vis ellipticine. Attempt has been made to correlate interaction energy studies with demethylation of ellipticine and the possible binding patterns.

Amsacrine binds in a cooperative manner to deoxyribonucleic acid.

The intercalative binding of the acridine antitumour drug 4'-(9-acridinylamino) methane-sulphonate-m-anisidine, a known inhibitor of nucleic acid synthesis, to native calf thymus DNA has been studied using optical titration method. Amsacrine (AMSA) exhibits positive cooperativity in their equilibrium binding to DNA as indicated by the positive slope in the initial region of the binding isotherms (Scatchard plots) under conditions simulating physiological ionic strengths. m-AMSA binds with a higher degree of cooperativity than o-AMSA. Although this correlates with the effectiveness of the drugs as antitumour agents, the exact relationship between the observation of cooperative binding and pharmacological activity is yet to be determined.

Mode of action of intercalators: a theoretical study.

Mode of action of some intercalators has been theoretically investigated on the basis of quantum mechanical perturbation method. Energies of H-bond interaction between drug chromophore and base pairs have been calculated in all possible orientations. The stacking energy has also been calculated with the base pairs. The effect of these interactions on specific recognition has also been discussed. On the basis of these studies, a model for the interaction of these drugs has been proposed. This explains the relative activities of acridine intercalators and satisfies the experimental observations.