Computational studies on statins photoactivity

Abstract

Abstract Statins are popular drugs widely prescribed to control hypercholesterolaemia and to prevent cardiovascular diseases. Synthetic statins constitute a group of pharmaceuticals which are very sensitive to exposure to light in both UVA and UVB ranges. Light, by causing drugs degradation, can essentially change their pharmaceutical properties leading even to the loss of therapeutic activity and/or to the formation of deleterious photoproducts. Drugs which exhibit photochemical reactivity may elicit undesired adverse effects. A detailed understanding of mechanisms involved in molecular basis of these effects origin is very important for evaluating the photobiological risk associated with therapy in which drugs prone to exposure to light are involved. In this work we critically discussed finding regarding the mechanisms of synthetic statins phototransformation. We showed inconsistency of some previously reported facts and revised earlier presented studies. We also completed the lack of information on pitavastatin photobehaviour. This all together resulted in proposal of new schemes for the statins photodecomposition. We reviewed data derived from both experimental and computational methods. Studies of photochemical problems by the use of theoretical methods enable getting insight into areas of some fascinating events that experimental techniques can touch only indirectly. Besides effect of light, phenomenon of statins’ sensitivity to pH and resulting implications were discussed. Statins undergo pH-dependent interconversion between their pharmacologically active hydroxy acid and inactive lactone forms, and it was shown that for both forms, drugs’ interactions should be considered. Knowledge of the statins interconversion mechanisms is important for understanding how differences in the structures of their molecules can affect the drugs’ activity.