Why Are the Majority of Active Compounds in the CNS Domain Natural Products? A Critical Analysis

被引：85

作者：

Bharate, Sonali S. ^{[1
]}

Mignani, Serge ^{[2
,3
,4
]}

Vishwakarma, Ram A. ^{[4
]}

机构：

[1] CSIR Indian Inst Integrat Med, PK PD Toxicol & Formulat Div, Preformulat Lab, Canal Rd, Jammu 180001, India

[2] Univ Paris 05, PRES Sorbonne Paris Cite, CNRS, Lab Chim & Biochim Pharmacol & Toxicol,UMR 860, 45 Rue St Peres, F-75006 Paris, France

[3] Univ Madeira, MMRG, CQM, Campus Penteada, P-9020105 Funchal, Portugal

[4] CSIR Indian Inst Integrat Med, Div Med Chem, Canal Rd, Jammu 180001, India

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2018年 / 61卷 / 23期

关键词：

CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; DOPAMINE-RECEPTOR AGONIST; DRUG DISCOVERY; ADENOSINE RECEPTORS; ALZHEIMERS-DISEASE; OROMUCOSAL SPRAY; MEDICINAL-PLANT; P-GLYCOPROTEIN; PHARMACOLOGY;

D O I：

10.1021/acs.jmedchem.7b01922

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Small-molecule natural products (NPs) have a long and successful track record of providing first-in-class drugs and pharmacophore (scaffolds) in all therapeutic areas, serving as a bridge between modern and traditional medicine. This trajectory has been remarkably successful in three key areas of modern therapeutics: cancers, infections, and CNS diseases. Beginning with the discovery of morphine 200 years ago, natural products have remained the primary source of new drugs/scaffolds for CNS diseases. In this perspective, we address the question: why are the majority of active compounds in the CNS domain natural products? Our analysis indicates that similar to 84% approved drugs for CNS diseases are NPs or NP-inspired, and interestingly, 20 natural products provided more than 400 clinically approved CNS drugs. We have discussed unique physicochemical properties of NPs and NP-inspired vis-a-vis synthetic drugs, isoform selectivity, and evolutionary relationship, providing a rationale for increasing focus on natural product driven discovery for next-generation drugs for neurodegenerative diseases.

引用

页码：10345 / 10374

页数：30

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