Rediscovery of natural compounds acting via multitarget recognition and noncanonical pharmacodynamical actions

Bizzarri, Mariano; Giuliani, Alessandro; Monti, Noemi; Verna, Roberto; Pensotti, Andrea; Cucina, Alessandra

doi:10.1016/j.drudis.2020.02.010

Cited by 15 publications

(16 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a consequence, natural products have become widely recognized as the future of therapeutic agent source, due to the enormous invaluable extracts, and are broadly accepted in the aid for conventional therapy [13]. Meanwhile, in comparison to synthetic source therapy, extracts from natural source are considered safe, easy to locate and access, reasonably cheap and with low incidence of adverse effects, thus, facilitating the surging diversion into phytomedicine [14,15]. Historically, traditional herbal medicine and their relative natural products have in practice been extensively tested in the treatments for Alzheimer's disease, diabetes mellitus, gynaecological and neurological illness, and several others disease, via the dietary consumption of the leaves, fruits, other body parts, and also the crude extracts from common plants in Nigeria [15,16].…”

Section: Graphical Abstract 1 Introductionmentioning

confidence: 99%

Citrullus lanatus natural product library: A hoard of viable potential inhibitor candidates for diabetes mellitus type II therapeutic target enzymes

Olowosoke¹,

Alaba²,

Adegboyega³

2022

World J. Adv. Res. Rev.

View full text Add to dashboard Cite

The ethnomedicinal function of several cucurbit species (cucumber, squash, melon, gourd, etc.) on diseases (i.e. diabetes, microbial infections, cancer, etc.), and as free radical scavengers have been reported. However, there remains infinitesimal record on citron watermelon broad use, which reflects the reason for wide oversight of underutilization, from lack of recognition for functional food crop development and commercialization. The objective of this study focus towards identifying the natural phytochemicals of C. lanatus on water melon molecules online database for insilico computational approach to screened for suitable antidiabetic lead, and construction of phylogenetic relatedness of target Type 2 Diabetes Mellitus proteins was conducted to predict reoccurrence of insilico analysis output with other homologous target proteins. The T2DM protein targets, phytochemical and standard inhibitory drugs are mined from different databases. Insilico docking analysis, and adme/toxicity profiling was virtually screened for the best fit. In additionally, phylogenetic relationship of the target proteins was aligned and construction with other homologous protein targets to predict the reoccurrence confidence of results on compounds. Seventeen phytochemicals out of the nineteen potential drug candidates substantially passed the profiling test. Also, homologous protein targets with > 90% bootstrap confidence are likely to produce a reoccurring insilico result. Thus, these phytochemicals fulfil all the enlisted criteria and it is suggestively determined to be suitable for the development of potent antidiabetic drugs. It is evident that phytochemicals from Citrullus lanatus produced satisfactory insilico output, and this reflect it to be a probable reservoir containing other potential therapeutic drug candidates for antidiabetic drug discovery and development. Additionally, derivatives can be developed for further effective screening result.

show abstract

Section: Graphical Abstract 1 Introductionmentioning

confidence: 99%

Citrullus lanatus natural product library: A hoard of viable potential inhibitor candidates for diabetes mellitus type II therapeutic target enzymes

Olowosoke¹,

Alaba²,

Adegboyega³

2022

World J. Adv. Res. Rev.

View full text Add to dashboard Cite

show abstract

“…Radicicol imitates HSP90's ADP-bound configuration and interacts similarly with Asp93 geldanamycin. Contrastingly, RD is oriented differently to GA when binding and has a higher degree of binding to the ATP pocket [ 71 , 78 ]. Although not as structurally remarkable as GA, RD also takes on a folded configuration, with an essentially perpendicular rather than parallel macrocycle and aromatic ring [ 78 ].…”

Section: Development Of Heat Shock Protein 90 Inhibitorsmentioning

confidence: 99%

“…Contrastingly, RD is oriented differently to GA when binding and has a higher degree of binding to the ATP pocket [ 71 , 78 ]. Although not as structurally remarkable as GA, RD also takes on a folded configuration, with an essentially perpendicular rather than parallel macrocycle and aromatic ring [ 78 ]. However, RD does not exhibit antitumour activity because of its rapid in vivo metabolism [ 69 ].…”

Section: Development Of Heat Shock Protein 90 Inhibitorsmentioning

confidence: 99%

Heat Shock Protein 90 (HSP90) Inhibitors as Anticancer Medicines: A Review on the Computer-Aided Drug Discovery Approaches over the Past Five Years

Magwenyane

Ugbaja

Amoako

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Cancer is a disease caused by the uncontrolled, abnormal growth of cells in different anatomic sites. In 2018, it was predicted that the worldwide cancer burden would rise to 18.1 million new cases and 9.6 million deaths. Anticancer compounds, often known as chemotherapeutic medicines, have gained much interest in recent cancer research. These medicines work through various biological processes in targeting cells at various stages of the cell’s life cycle. One of the most significant roadblocks to developing anticancer drugs is that traditional chemotherapy affects normal cells and cancer cells, resulting in substantial side effects. Recently, advancements in new drug development methodologies and the prediction of the targeted interatomic and intermolecular ligand interaction sites have been beneficial. This has prompted further research into developing and discovering novel chemical species as preferred therapeutic compounds against specific cancer types. Identifying new drug molecules with high selectivity and specificity for cancer is a prerequisite in the treatment and management of the disease. The overexpression of HSP90 occurs in patients with cancer, and the HSP90 triggers unstable harmful kinase functions, which enhance carcinogenesis. Therefore, the development of potent HSP90 inhibitors with high selectivity and specificity becomes very imperative. The activities of HSP90 as chaperones and cochaperones are complex due to the conformational dynamism, and this could be one of the reasons why no HSP90 drugs have made it beyond the clinical trials. Nevertheless, HSP90 modulations appear to be preferred due to the competitive inhibition of the targeted N-terminal adenosine triphosphate pocket. This study, therefore, presents an overview of the various computational models implored in the development of HSP90 inhibitors as anticancer medicines. We hereby suggest an extensive investigation of advanced computational modelling of the three different domains of HSP90 for potent, effective inhibitor design with minimal off-target effects.

show abstract

“…Regions of higher and lower solute concentrations also coexist in solution, and predicting biological effects based solely on their chemical composition is not straightforward (Bizzarri et al 2020). In addition to the classical pharmacodynamic mechanisms of action, plant-derived products also induce biological responses by physical and unconventional pharmacodynamics mechanisms, such as supramolecular chemistry, enhancement of absorption, changes on surface tension, and chelating effects on toxic ions, among others, and they should be integrated within network models currently in use (Bizzarri et al 2020). This finding opens new venues for investigating the biological effects of herbal medicines through the concept of antifragility.…”

Section: Exploring System Biology and Antifragilitymentioning

confidence: 99%

Paving New Roads Towards Biodiversity-Based Drug Development in Brazil: Lessons from the Past and Future Perspectives

Braga

2021

Rev. Bras. Farmacogn.

View full text Add to dashboard Cite

Although Brazil gathers two fundamental features to occupy a leading position on the development of biodiversity-based medicines, the largest flora on earth and a broad tradition on the use of medicinal plants, the number of products derived from the national genetic heritage is so far modest, either as single drugs or as herbal medicines. This article highlights some aspects that may have contributed to the low rates of success and proposes new insights for innovation. We initially approach the use of medicinal plants in Brazil, molded by its ethnic diversity, and the development of the local pharmaceutical industry. A discussion of some governmental initiatives to support plant-based drug development is then presented. Employing the economic concept of "middle-income trap," we further propose that Brazil is stuck in a "middle-level science trap," since the increase in the number of scientific publications that launched the country to an intermediate publishing position has not been translated into drug development. Two new approaches to escape from this trap are presented, which may result in innovative drug development. The first is based on the exploitation of the antifragility properties of herbal products aiming to investigate non-canonical pharmacodynamics mechanisms of action, aligned with the concepts of system biology. The second is the manufacture of herbal products based on the circular economy principles, including the use of byproducts for the development of new therapeutical agents. The adoption of these strategies may result in innovative phytomedicines, with global competitiveness.

show abstract

Rediscovery of natural compounds acting via multitarget recognition and noncanonical pharmacodynamical actions

Cited by 15 publications

References 76 publications

Citrullus lanatus natural product library: A hoard of viable potential inhibitor candidates for diabetes mellitus type II therapeutic target enzymes

Citrullus lanatus natural product library: A hoard of viable potential inhibitor candidates for diabetes mellitus type II therapeutic target enzymes

Heat Shock Protein 90 (HSP90) Inhibitors as Anticancer Medicines: A Review on the Computer-Aided Drug Discovery Approaches over the Past Five Years

Paving New Roads Towards Biodiversity-Based Drug Development in Brazil: Lessons from the Past and Future Perspectives

Contact Info

Product

Resources

About