Target-based Exploration Of Anti-AD Traditional Chinese Medicinal Compounds

Alzheimer' disease(AD)is an ultimately fatal degenerative brain disorder with high morbidity and mortality which has profound social and economic consequences.There are only five drugs for AD on the market and haven't been any novel effective medicines for quite a few years.Therefore,it is of great signiflcance for prevention,treatment and recovery of AD to explore effective anti-AD drugs.Chinese medicinal plants were used for various diseases treatment and screening herbal remedies are a way to develop new drugs.The traditional Chinese medicine has been used to treat diseases for nearly a thousand years.More than 2000 medicinal plants are recorded.As a result,traditional Chinese herbs are a valuable resource for the treatment of AD.However,it takes a long time and a lot of manpower and financial resources to explore the effective small molecule compounds in traditional Chinese herbal plants relying on experiment.So,we try to use computational analysis to seek potentially promising drug candidates for the treatment of Alzheimer's disease.Totally 30438 compounds have plant information in TCM Database@Taiwan(8529 Chinese plant ID and more than 60000 active compound ID contained from Chinese plants)and 30 known anti-AD targets from Thomson Reuters Integrity database undergo molecular docking so as to obtain 1476 candidate anti-AD compounds which have good docking values.We made a further analysis of 1476 molecular compounds as drug candidates for treatment of AD.The structural similarity between 1476 compounds and existing drugs in Drugbank database was measured(Tc=1).17 candidate anti-AD compounds are structurally identical with 14 existing drugs in which part of them have been reported in anti-AD research.So,they could be considered anti-AD drugs.According to the characteristics of molecular fingerprint for candidate anti-AD compounds,the candidate compounds were clustered.And every cluster compounds have similar properties.All the compounds in cluster center contain the carbocyclic structure.Five approved drugs used for AD also contain the carbocyclic structure.Different clusters have different numiber of compounds and different targets.Alzheimer's disease is known as senile dementia in China.And just 101 clinical related articles were collected from more than l0000 senile dementia related articles.We collected 141 anti-AD traditional Chinese plants from 101 clinical prescriptions.Every target has its best associated plant which has the most compounds docking with the target.There are total 16 plants best associated with 30 targets.The 5 most frequent plants of them associated with 16 targets are anti-AD traditional Chinese plants.After ADMET fiher,there are 11 anti-AD compounds with favorable properties remained.The 11 compounds have good pharmacokinetic molecular properties offering an opportunity to develop new drug candidates.Five properties,including aqueous solubility,blood brain barrier penetration(BBB),human intestinal absorption(HIA),plasma protein binding(PPB)and hepatotoxicity were used to filter the compounds.The corresponding plants of 7 compounds from the 11 compounds with favorable properties were anti-AD plants.Through the research of this paper,we aimed to find potentially promising drug candidates from Chinese medicinal plants for AD,which has important guiding significance for the development and design of anti-AD drag.