Design,Synthesis,Antifungal And Cardiovascular Protective Activity Study Of Active Natural Product Flavonoids

In this research we have prepared rapidly and efficiently a series of 3,4-diarylpyrazoles and 3,5-diarylpyrazoles from flavonoids with hydrazine and its derivatives by chemical engineering method.We have synthesized 44 compounds(6-9,20-24,25-29,30a-39a,41a-46a,34b,35b,37b-40b,42b-44b,47-51)and assayed all synthesized compounds against C.albicans SC5314 and DSY654 and analysized the structure-activity relationship.Finally we screened out 13 compounds which displayed antifungal activity,of which compounds 6,20,21 and 29 are the most potent antifungal agents.Moreover,we also assyed all compounds against clinical drug-resistant C.albicans 28A and we screened out 9 compounds which displayed antifungal activity,of which compounds 6,20,25,28 and 32a displayed excellent reversal activity of FLC resistance.We found that 3,4-diaylpyrazloe moiety is necessary to keep antifungal activity.Introduction of two methoxy groups at C-4' and C-6' on arene A led to the most potent compound 20,and introduction of substituents to at N atom on arene B made antifungal activity decreasing or lost.We found that 3,5-diarylpyrazoles 20,25,28 and 32a displayed excellent reversal activity of FLC resistance.When hydroxyl groups exist at C-2',C-4' and C-6' on arene A compounds 20 showed better reversal activity against clinical isolate 28A with FICI value of 0.075.Further,when hydroxyl groups exist at C-2',C-4' and C-6'on arene A and at C-4" on arene C compounds 28 displyed the most potent antifungal activity with FICI value of 0.012.Hence,we guess that phenolic hydroxyl groups are essential to improve the reversal activity of FLC resistance.3,5-diarylpyrazoles are better than 3,5-diarylpyrazoles in aspect of antifungal activity.In addition,to improve water solubility and bioavailability of puerarin our group also modified puerarin by reduction.with Pd/C and LiBH4 and gained ten novel compounds(1-6,8-11).We found compounds 3,4 and 11 displayed better activities than puerarin in aspect of increasing coronary blood flow,relaxation of aortic rings and decreasing ischemia reperfusion injury.