Naslov
Theoretical study of psychoactive drugs. 2. Conformational analysis of medazepam by semiempirical quantum chemical methods.

Autori
Funar-Timofei, Simona ; Ionescu, Daniela ; Pokrić, Biserka

Izvornik
Timişoara Medical Journal (1583-5251) 56 (2006), 2; 63-66

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, kongresno priopcenje, znanstveni

Ključne riječi
conformation; drug; medazepam; molecular mechanics; toxicity

Sažetak
Objectives: Medazepam is a benzodiazepine derivative used in the treatment of anxiety. It has sedative, myorelaxant, and anticonvulsant properties. It has generally been considered as being safe and of low toxicity drug. With long-term use, tolerance, dependence and withdrawal effects can become major disadvantages. Medazepam structure can be related to its toxicity. Methods: The structure of medazepam was studied by molecular mechanics using the MM2 force field and by the AM1 and PM3 quantum chemical methods. Results: According to the experimental crystallographic X-ray data the medazepam structure exists in an enantiomorphous pairs (conformational chirality). Several medazepam conformations were generated by molecular mechanics calculations to find out the minimum energy structures which were further minimized by the AM1 and PM3 semiempirical methods. One stable medazepam conformer was obtained whose geometry was then compared to the geometries of the two enantiomers mentioned in the X-ray crystallographic study, by statistical analysis. The semiempirical molecular orbital AM1 method gave better statistical results in comparison to the PM3 method. Conclusions: Medazepam structure obtained by the AM1 method is in agreement with the crystallographic data and can be further used in structure-toxicity studies.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA