Synthesis And Vasodilative Activity Of Tanshinone ⅡA Derivatives

Danshen, the root of Salvia miltiorrhiza, is one of the commonly used traditional Chinese medicines which has a definite effect on cardiovascular and cerebrovascular diseases. Tanshinone ⅡA is one of the major lipid-soluble components extracted from danshen which shows the significant effects in cardiovascular system, antiarrhythmic activity, vasodilation and cardi protection, etc. In this paper, the synthesis of tanshinone ⅡA derivatives was investigated. Vasodilation activity of them was valuated on the vascular aorta smooth muscle from Wistar rats.1. The synthesis of tanshinone ⅡA derivatives was investigated. We want to improve the polarity and activity of tanshinone ⅡA.1-Br tanshinone ⅡA was synthesized by the free radical reaction of tanshinone IIA and NBS in the presence of BPO. In this paper, a new series of tanshinone ⅡA derivatives were synthesized through the reaction of brominated tanshinone ⅡA and aromatic acids in the presence of K2CO3. Twenty-three compounds were synthesized, and all of them were novel. During the experiment, all the polarity of compounds were detected by TLC with at least two different developing systems. The results of TLC showed that all the compounds are more polar than tanshinone ⅡA.2. Vasodilation activity of tanshinone ⅡA derivatives were valuated on the vascular thoracic aorta smooth muscle from Wistar rats. We want to screen some compounds which have better vasodilator activity and discuss the structure-activityrelationships by the pharmacological activity of tanshinone ⅡA derivatives research. Vasodilative activities for synthesized compounds were valuated in vitro on the contractile response of vascular thoracic aorta smooth muscle from male Wistar rats pre-contracted with norepinephrine bitartrate (1×106M) according to the known standard procedure. The results were presented in terms of percentage of the maximal control norepinephrine-induced responses. Most of compounds showed a concentration-dependent inhibition on the contractile response of norepinephrine. Especially P9, P10, P16and P21, exhibited better activity, and compared to their raw materials, the relaxant effects of bioactive products (9,10,16and21) were improved in varying degrees. The structure-activity relationship showed that the benzoic acids substituted derivatives presented better pharmacological vasodilative properties than that of phenylacetic acids substituted derivatives. Most methoxy-substituing derivatives presented good pharmacological vasodilative properties, suggesting that, methoxy has a distinct role to improve the vasodilative activity. In addition, the electrondonatinggroup substituted derivatives presented better vasodilative activity than the electronattractinggroup substituted derivatives.The preliminary structure-activity relationship showed that it is valuable to develop potent vasodilatve activity of tanshinone ⅡA derivatives.