Microbial resistance to classical antibiotics and its rapid progression have raised serious concern in the treatment of infectious diseases. Recently, many studies have been directed towards finding promising solutions to overcome these problems. Phytochemicals have exerted potential antibacterial activities against sensitive and resistant pathogens via different mechanisms of action. In this review, we have summarized the main antibiotic resistance mechanisms of bacteria and also discussed how phytochemicals belonging to different chemical classes could reverse the antibiotic resistance. Next to containing direct antimicrobial activities, some of them have exerted in vitro synergistic effects when being combined with conventional antibiotics. Considering these facts, it could be stated that phytochemicals represent a valuable source of bioactive compounds with potent antimicrobial activities.

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Review on plant antimicrobials: a mechanistic viewpoint

Coumarin compounds represent an important type of naturally occurring and synthetic oxygen-containing heterocycles with typical benzopyrone framework. This type of special benzopyrone structure enables its derivatives readily interact with a diversity of enzymes and receptors in organisms through weak bond interactions, thereby exhibit wide potentiality as medicinal drugs. So far, some coumarin-based drugs such as anticoagulant and antineurodegenerative agents have been extensively used in clinic. Coumarin-containing supramolecular medicinal agents as a new increasing expansion of supramolecular chemistry in pharmaceutical science have also been actively investigated in recent years. Coumarin-derived artificial ion receptors, fluorescent probes and biological stains are growing quickly and have a variety of potential applications in monitoring timely enzyme activity, complex biological events as well as accurate pharmacological and pharmacokinetic properties. This review provides a systematic summary and insight of the whole range of medicinal chemistry in the current developments of coumarin compounds as anticoagulant, antineurodegenerative, anticancer, antioxidative, antibacterial, antifungal, antiviral, antiparasitic, antiinflammatory and analgesic, antidiabetic, antidepressive and other bioactive agents as well as supramolecular medicinal drugs, diagnostic agents and pathologic probes, and biological stains. Some rational design strategies, structure-activity relationships and action mechanisms are discussed. The perspectives of the future development of coumarinbased medicinal chemistry are also presented.

Current Developments of Coumarin Compounds in Medicinal Chemistry

Current developments of coumarin-based anti-cancer agents in medicinal chemistry

Coumarin heterocyclic derivatives: chemical synthesis and biological activity

Coumarin hybrids as novel therapeutic agents.

Coumarins are of many different structures. They constitute an important class of pharmacological agents possessing a range of different physiological activities including anti-cancer, anti-oxidant, anti- inflammation, anti-HIV, anti-coagulant, anti-bacterial, analgesic and comparative immune-modulation. Recently, coumarins have attracted intense research interest. Of great interest is the possibility that this class of molecules could be a source of drugs for the therapy of several diseases. These include recent insights into inhibiting cell proliferation by interfering with mitotic spindle microtubule function, decrease Matrix Metalloproteinase (MMP) activity, block the cell cycle in the S or G2/M phases to interfere with processes of cell division, suppress O2(-) generation in leukocytes, inhibit different protein kinases, modulate the signalings, induce carcinogen-detoxifying enzymes glutathione S-transferases (GSTs) and/or NAD(P)H quinine oxidoreductase (NQO1), suppress the phosphorylation of Akt/PKB as a mechanism inhibiting inflammation, progress in structure modification to increase in anti-fungal action, to broaden against bacteria spectrum, to enhance inhibiting activities of nitric oxide synthase (NOS) and cyclooxygenase (COX), to strengthen anti-oxidant activity and to exhibite a much higher cytotoxicity against human umbilical vein endothelial cell (HUVEC). With fewer non-hemorrhagic side effects than the indanedione derivatives, they can be applied as an oral anticoagulant commonly for preventing venous thromboembolism following orthopedic surgery, recurrent myocardial infarction and the treatment of systemic embolism in atrial fibrillation, together with the significant advances in the basis of drug action. It is therefore useful to build up some correlations with the data available in order to better explore the molecular and cellular mechanism of coumarin action in the treatment of diseases. This review will focus on recent advances in molecular and cellular mechanisms of coumarin action involved with the relationship between structure and activity.

The Structure and Pharmacological Functions of Coumarins and Their Derivatives

Alzheimer’s disease (AD) is a chronic, neurodegenerative illness characterized by forgetfulness, cognitive impairment, and the progressive loss of a variety of other brain functions as well as daily life independence. By 2050, the existing 47 million AD sufferers are predicted to grow to 152 million, with major economic, medical, and societal implications. The pathophysiology of Alzheimer’s disease is still unknown, and there is no cure or treatment that can stop the illness from progressing altogether. Alzheimer’s disease must be detected early in order to be effectively managed. An emerging detection methodology includes deep learning approaches that have demonstrated promising results; nonetheless, effective implementations in real-world settings must combine high accuracy, quick processing time, and scalability for a variety of demographics or populations. An AlexNet convolutional neural network (CNN) based classification model using magnetic resonance imaging (MRI) images available from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). This AlexNet model was then applied to the ADNI dataset to classify four different stages of AD. The model was then tested on test datasets to evaluate the accuracy of the model per stage: 95.5% for early dementia, 95.1% for moderate dementia, 89.3% for no dementia, and 92.7% for late dementia. In the visualization results, the ventricles and outer regions were identified as key regions for classification. These CNN recognition results were further accurately interpreted with the newly developed class activation mapping (CAM), allowing for the interpretability of given diagnoses.

William Xu

Papers

The Structure and Pharmacological Functions of Coumarins and Their Derivatives

Class Activation Mapping Enhanced AlexNet Convolutional Neural Networks for Early Diagnosis of Alzheimer’s Disease