Mini Reviews in Medicinal Chemistry - Volume 21, Issue 18, 2021

Aging is an unavoidable process, leading to cell senescence due to physiochemical changes in an organism. Anti-aging remedies have always been of great interest since ancient times. The purpose of anti-aging activities is to increase the life span and the quality of life. Anti-aging activities are primarily involved in the therapies of age-related disorders such as Parkinson's Disease (PD), Alzheimer's Disease (AD), cardiovascular diseases, cancer, and chronic obstructive pulmonary diseases. These diseases are triggered by multiple factors that are involved in numerous molecular pathways including telomere shortening, NF-ΚB pathway, adiponectin receptor pathway, insulin, and IGF signaling pathway, AMPK, mTOR, and mitochondria dysfunction. Natural products are known as effective molecules to delay the aging process through influencing metabolic pathways and thus ensure an extended lifespan. These natural compounds are being utilized in drug design and development through computational and high throughput techniques for effective pro-longevity drugs. A comprehensive study on natural compounds demonstrating their anti-aging activities along with databases of natural products for drug designing was executed and summarized in this review article.

Constant research on natural products has generated, over time, a large number of compounds with the potential to be evaluated in several biological tests and subsequently have been cataloged in databases that allow other researchers to perform virtual screenings of activity in various biological systems. This considerably reduces the time for the development of new drugs. This review describes the main databases of natural products available for searching bioactive compounds. It also describes the main features of virtual screening strategies for the identification of molecules with the potential to be used as new drugs. In addition, a search was made in the Web of Science database, using the search term "Virtual screening of natural products databases" from 2003 to 2018. The search criterion resulted in 230 articles, which had their abstracts evaluated with pertinence to the criteria required for this work, which are: a) be a research article; b) performing a virtual screening on databases of natural products or containing natural products; and c) works that identified drug candidate molecules. Based on these criteria, the bibliographic review on the topic was excluded. After this analysis, 104 works were selected for this review. We selected relevant papers describing the potential drug candidates that were distributed in 15 classes, of which the anticancer, antibacterial and anti-inflammatory hits were the most abundant. The works showing efforts to search for new molecules against various other diseases in distinct biological systems were also described. In this way, this work shows an overview of several methodologies and we hope they can help and inspire the development of new research to improve people's quality of life.

Phytocompounds isolated from plants are well appraised for their broad pharmacological propensities in several pathologies. One key benefit of phytoconstituents is their relatively low toxicity and adverse effects. Nonetheless, poor solubility, permeation, and poor specificity at the target site tend to hinder its therapeutic efficacy. Hence, novel technologies for drug delivery systems are being developed via the use of various nanoformulation strategies to overcome these challenges and give uniform medication focusing at the dynamic site in desired concentration and improved therapeutic efficacy. Such approaches comprise of novel drug delivery systems (NDDS). The utilisation of herbal formulations for NDDS is more beneficial and advantageous as opposed to others. The utilisation of ethosome, liposome, emulsion, phytosomes, microsphere, and strong lipid nanoparticles of herbal formulation has improved the remedial impacts of plant extricates. With the utilisation of all these, directed delivery of the formulation is accomplished, because of which the formulation exhibits impact on the site, and its’ bioavailability is, likewise, expanded. With these novel medication conveyance frameworks, the actives and concentrates, which are utilised as part of natural formulations, exhibit a sustained release, enhancement in stability, improved therapeutic efficacy, and protection from toxicity. The primary motivation behind creating alternative drug delivery technologies is to expand the effectiveness of drug conveyance and safety in the process and give more comfort to the patient. In this review, the importance of various phytocompounds in the delivery of drugs is highlighted as well as their importance in reducing the risk or diseases.

Nature has always proved to be a significant reservoir of bioactive scaffolds that have been used for the discovery of drugs since times. Medicinal plants continue to be a solid niche for biologically active and therapeutically effective chemical entities, opening up new avenues for the successful treatment of several human diseases. The contribution of plant-derived compounds to drug discovery, either in their original or in the semi-synthetic derivative form, extends far back in time. This review aims to focus on the sources, biological, and pharmacological profile of a pharmacologically active plant-derived coumarin, osthole, which is an important component of numerous remedial plants such as Cnidium monnieri. Several studies have revealed that osthole possess pharmacological properties such as anticancer, antioxidant, anti-hyperglycemic, neuroprotective, and antiplatelet. Osthole has been reported to regulate various signaling pathways, which in turn modulate several apoptosis-related proteins, cell cycle regulators, protein kinases, transcriptional factors, cytokines, and growth receptors affiliated with inflammation, proliferation and several other ailments. Osthole is known to halt proliferation and metastasis of cancerous cells by arresting the cell cycle and inducing apoptosis. The data in this review paper supports the pharmacological potential of osthole but further experimentation, biosafety profiling and synergistic effects of this compound need to be focused by the researchers to understand the full spectrum of pharmacological potential of this therapeutically potent compound.

Throughout the ages, compounds collected and/or isolated from natural sources have been the basic source of medicinal agents against a variety of diseases. The data generated from the extensive experimentation conducted in research labs from all over the world has diversity and complexity, and the challenging task for database creators is to store, represent, and exchange this data. The natural product database is required to be easily accessible for supporting drug discovery efforts. A possible solution for this is provided by chemical databases based on bio- and chem-informatic approaches. Some of the anti-cancer natural product databases, along with the tools required for creating and accessing the information, are discussed here.

Introduction: Brucella melitensis is a facultative intracellular bacterial pathogen that causes abortion in goats and sheep and Malta fever in humans. In humans, chronic infection occurs through contact with infected animals or their waste products. Methods: The subtractive genomic approach is considered as a powerful and useful method for the identification of potential drug and vaccine targets. In this study, an attempt has been made through a subtractive proteomic strategy to identify novel drug targets in Brucella melitensis strains. Total 2604 core proteins of 56 strains of B. melitensis were taken, of which 545 non-human homologs were found to be essential for pathogen growth. Metabolic pathway analysis of these essential proteins revealed that 129 proteins are exclusively involved in 21 unique metabolic pathways in B. melitensis reference strain. Results: Of these, 31 proteins were found to be involved in 10 metabolic pathways that are unique to the pathogen. We selected Nitrate reductase subunit-β, Urease subunit α-2, Pantoate-β-alanine ligase, Isochorismatase, 2-dehydro-3-deoxyphosphooctonate aldolase and Serine O-acetyltransferase as drug targets in Brucella melitensis strains. Among these druggable targets, we selected only Pantoate-β- alanine ligase as high confidence target based on intensive literature curation, which is nonhomologous to the human gut metagenome involved in biosynthesis of secondary metabolites pathway. Pantothenate synthetase is the best chemotherapeutic target to combat Brucellulosis. Conclusion: Furthermore, in vitro and in vivo validation is needed for the evaluation of lead compounds against Brucella melitensis strains.

In silico ADMET models have progressed significantly over the past ~4 decades, but still, the pharmaceutical industry is vexed by the late-stage toxicity failure of lead molecules. This problem of late-stage attrition of the drug candidates because of adverse ADMET profile motivated us to analyze the current role and status of different in silico tools along with the rise of machine learning (ML) based program for ADMET prediction. In this review, we have differentiated AI from traditional in silico tools because, unlike traditional in silico tools where the final decision is made manually, AI automates the decision-making prerogative of humans. Due to the large volume of literature in this field, we have considered the publications in the last two years for our review. Overall, from the literature reviewed, deep neural networks (DNN) algorithm or deep learning seems to be the future of ML-based prediction models. DNNs have shown the ability to learn from more complex data and this gives DNN an edge over other ML algorithms to be applied for ADMET prediction. Our result also suggests that we need closer collaboration between the ADMET data generators and those who are employing ML-based tools on this generated data to build predictive models, so that more accurate models could be developed. Overall, our study concludes that ML is still a work in progress and its appetite for data has not been sated yet. It needs loads of more quality data and still some time to prove its real worth in predicting ADMET.

Background: Linum usitatissimum or flax has been broadly utilized in numerous milieus worldwide as a primeval medicinal plant because of its health benefits in diverse types of diseases. Objective: The objective of this review is to assemble the latest information on the botanical description, distribution, conventional uses, and biochemical constituents, along with the pharmacological activities and toxicity of flax. Methods: For this purpose, data on Linum was accumulated from scientific journals, books, and worldwide acknowledged scientific databases via a library and electronic search. Results: Phytochemical analysis showed that the major chemical constituents of L. usitatissimum are ω-3 fatty acid, phytoestrogenic-lignans (secoisolariciresinol diglucoside-SDG), phenols, flavonoids, sterols, proteins, antioxidants as well as various soluble and insoluble fibres. Among them, secoisolariciresinol diglucosides (SDG) are the major bioactive compounds of L. usitatissimum with prospective pharmacological accomplishments. Pure compounds and crude extracts isolated from L. usitatissimum exhibited significant anti-cancer, antioxidant, anti-microbial, anti-inflammatory, anti-obesity, antidiabetic, anti-diarrheal, anti-malarial, hepato-protective, reno-protective, immunosuppressive, antiarrhythmic, and cognitive effects. Studies indicated that the toxicological effect from the consumption of flaxseed is because of its cyanogenic glycosides, linatine, and cadmium, but the level does not seem to be adequately concentrated to contribute to any physiological impact. Conclusions: Further studies are expected to comprehend the detailed mode of action of its dynamic constituents as potent therapeutics and to completely reveal its preventive and healing potentials.

Glioma is a prevalent primary tumor of the brain and spinal cord. Several biological pathways play an important role in the pathogenesis of glioma, including apoptosis, autophagy, cell cycle arrest, migration, and invasion. The low efficacy of chemotherapy and radiation therapy has forced researchers to evaluate alternative treatments for glioma. In this regard, flavonoids have been studied. Resveratrol is a flavonoid with distinct pharmacological activities that has been used in the treatment of various diseases. Several recent studies have also focused on its therapeutic efficacy against glioma. Resveratrol exerts its pharmacological attributes by regulating various molecular and cellular pathways. Here, we review contemporary knowledge in support of the use of resveratrol in the treatment of glioma and its effects on various molecular and cellular mechanisms.