scholarly journals Potential Pharmaceutical Application of Endemic Plants: When will Sri Lanka Understand the Economic Value Chain?

2021 ◽  
Vol 24 (02) ◽  
Author(s):  
Veranja Karunaratne
Keyword(s):  
Natural Products ◽  
Value Chain ◽  
Wide Spectrum ◽  
Economic Value ◽  
Main Concern ◽  
Natural Origin ◽  
Pharmaceutical Application ◽  
Discovery Research ◽  
Compound Libraries ◽  
Drug Discovery Research

Small molecules has been a main concern in the pharmaceutical industry for as long as they have existed. Enormous libraries of compounds have been collected and they in turn nurture drug discovery research. For example, big pharma, has in their compound libraries ranging from 500,000 to several million. Examining the drugs in the market, it is clear from where most are arriving: natural origin; out of the 1,328 new chemical entities approved as drugs between 1981 and 2016, only 359 were purely of synthetic origin. In the list of remaining ones, 326 were “biologics”, and 94 were vaccines. Importantly, 549 were from natural origin or arose motivated from natural compounds. Furthermore, anticancer compounds arising during the same period (1981–2014), only 23 were purely synthetic (Newman and Cragg, 2016). Natural origin can count for three categories: unaltered natural products; distinct mixture of natural products and natural product derivatives isolated from plants or other living organisms such as fungi, sponges, lichens, or microorganisms; and products modified through application of medicinal chemistry. There are many examples covering a wide spectrum of diseases: anticancer drugs such as docetaxel (Taxotere™), paclitaxel (Taxol™), vinblastine, podophyllotoxin (Condylin™), or etoposide; steroidal hormones such as progesterone, norgestrel, or cortisone; cardiac glycosides such as digitoxigenin; antibiotics like penicillin, streptomycin, and cephalosporins.

scholarly journals Modern Approaches in the Discovery and Development of Plant-Based Natural Products and Their Analogues as Potential Therapeutic Agents

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 349
Author(s):  
Asim Najmi ◽  
Sadique A. Javed ◽  
Mohammed Al Bratty ◽  
Hassan A. Alhazmi
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
Therapeutic Agents ◽  
Throughput Capacity ◽  
Scientific Interest ◽  
Comprehensive Overview ◽  
Natural Sources ◽  
Discovery Research ◽  
Drug Discovery Research

Natural products represents an important source of new lead compounds in drug discovery research. Several drugs currently used as therapeutic agents have been developed from natural sources; plant sources are specifically important. In the past few decades, pharmaceutical companies demonstrated insignificant attention towards natural product drug discovery, mainly due to its intrinsic complexity. Recently, technological advancements greatly helped to address the challenges and resulted in the revived scientific interest in drug discovery from natural sources. This review provides a comprehensive overview of various approaches used in the selection, authentication, extraction/isolation, biological screening, and analogue development through the application of modern drug-development principles of plant-based natural products. Main focus is given to the bioactivity-guided fractionation approach along with associated challenges and major advancements. A brief outline of historical development in natural product drug discovery and a snapshot of the prominent natural drugs developed in the last few decades are also presented. The researcher’s opinions indicated that an integrated interdisciplinary approach utilizing technological advances is necessary for the successful development of natural products. These involve the application of efficient selection method, well-designed extraction/isolation procedure, advanced structure elucidation techniques, and bioassays with a high-throughput capacity to establish druggability and patentability of phyto-compounds. A number of modern approaches including molecular modeling, virtual screening, natural product library, and database mining are being used for improving natural product drug discovery research. Renewed scientific interest and recent research trends in natural product drug discovery clearly indicated that natural products will play important role in the future development of new therapeutic drugs and it is also anticipated that efficient application of new approaches will further improve the drug discovery campaign.

scholarly journals Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform

2019 ◽  
Vol 24 (3) ◽  
pp. 346-361 ◽  
Author(s):  
Carolina B. Moraes ◽  
Gesa Witt ◽  
Maria Kuzikov ◽  
Bernhard Ellinger ◽  
Theodora Calogeropoulou ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Trypanosoma Brucei ◽  
Value Chain ◽  
Neglected Tropical Diseases ◽  
World Health ◽  
Synthetic Compound ◽  
Antiparasitic Activity ◽  
Compound Libraries ◽  
Health Organization

According to the World Health Organization, more than 1 billion people are at risk of or are affected by neglected tropical diseases. Examples of such diseases include trypanosomiasis, which causes sleeping sickness; leishmaniasis; and Chagas disease, all of which are prevalent in Africa, South America, and India. Our aim within the New Medicines for Trypanosomatidic Infections project was to use (1) synthetic and natural product libraries, (2) screening, and (3) a preclinical absorption, distribution, metabolism, and excretion–toxicity (ADME-Tox) profiling platform to identify compounds that can enter the trypanosomatidic drug discovery value chain. The synthetic compound libraries originated from multiple scaffolds with known antiparasitic activity and natural products from the Hypha Discovery MycoDiverse natural products library. Our focus was first to employ target-based screening to identify inhibitors of the protozoan Trypanosoma brucei pteridine reductase 1 ( TbPTR1) and second to use a Trypanosoma brucei phenotypic assay that made use of the T. brucei brucei parasite to identify compounds that inhibited cell growth and caused death. Some of the compounds underwent structure-activity relationship expansion and, when appropriate, were evaluated in a preclinical ADME-Tox assay panel. This preclinical platform has led to the identification of lead-like compounds as well as validated hits in the trypanosomatidic drug discovery value chain.

Synthetic Strategies and Biological Potential of Coumarin-Chalcone Hybrids: A New Dimension to Drug Design

2020 ◽  
Vol 24 (4) ◽  
pp. 402-438
Author(s):  
Sharda Pasricha ◽  
Pragya Gahlot
Keyword(s):  
Drug Discovery ◽  
Chemical Potential ◽  
Wide Spectrum ◽  
Biological Properties ◽  
Sar Studies ◽  
Discovery Research ◽  
Biological Potential ◽  
Drug Discovery Research ◽  
Hybrid Molecules ◽  
Agent Development

Privileged scaffolds are ubiquitous as effective templates in drug discovery regime. Natural and synthetically derived hybrid molecules are one such attractive scaffold for therapeutic agent development due to their dual or multiple modes of action, minimum or no side effects, favourable pharmacokinetics and other advantages. Coumarins and chalcone are two important classes of natural products affording diverse pharmacological activities which make them ideal templates for building coumarin-chalcone hybrids as effective biological scaffold for drug discovery research. Provoked by the promising medicinal application of hybrid molecules as well as those of coumarins and chalcones, the medicinal chemists have used molecular hybridisation strategy to report dozens of coumarin- chalcone hybrids with a wide spectrum of biological properties including anticancer, antimicrobial, antimalarial, antioxidant, anti-tubercular and so on. The present review provides a systematic summary on synthetic strategies, biological or chemical potential, SAR studies, some mechanisms of action and some plausible molecular targets of synthetic coumarin-chalcone hybrids published from 2001 till date. The review is expected to assist medicinal chemists in the effective and successful development of coumarin- chalcone hybrid based drug discovery regime.

scholarly journals Economic drug discovery and rational medicinal chemistry for tropical diseases

2005 ◽  
Vol 77 (11) ◽  
pp. 1957-1964 ◽  
Author(s):  
Kelly Chibale
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Third World ◽  
Medicinal Chemistry ◽  
Cysteine Proteases ◽  
Biological Targets ◽  
Antimalarial Agents ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Selection Of

In order to fulfill research objectives around target-based drug discovery in the field of anti-infective agents that are prevalent mainly in poor Third World countries, selection of biological and chemical targets is guided by economic drug discovery and rational medicinal chemistry. Selection of biological targets of therapeutic relevance in multiple disease-causing organisms, as well as the use of natural products and existing drugs as chemical scaffolds for the discovery and design of novel therapeutics should be viable strategies underpinning drug discovery research in poor Third World countries. In this regard, biological targets of interest to our program include disulfide reductases and cysteine proteases (CPs), while chemical scaffolds include existing antimalarial agents and natural products.

Epigenetic Target Prediction with Accurate Machine Learning Models

2021 ◽  
Author(s):  
Norberto Sánchez-Cruz ◽  
Jose L. Medina-Franco
Keyword(s):  
Machine Learning ◽  
Small Molecules ◽  
Predictive Models ◽  
Large Scale ◽  
Target Prediction ◽  
Quantitative Measure ◽  
Learning Models ◽  
Discovery Research ◽  
Drug Discovery Research ◽  
Machine Learning Models

<p>Epigenetic targets are a significant focus for drug discovery research, as demonstrated by the eight approved epigenetic drugs for treatment of cancer and the increasing availability of chemogenomic data related to epigenetics. This data represents a large amount of structure-activity relationships that has not been exploited thus far for the development of predictive models to support medicinal chemistry efforts. Herein, we report the first large-scale study of 26318 compounds with a quantitative measure of biological activity for 55 protein targets with epigenetic activity. Through a systematic comparison of machine learning models trained on molecular fingerprints of different design, we built predictive models with high accuracy for the epigenetic target profiling of small molecules. The models were thoroughly validated showing mean precisions up to 0.952 for the epigenetic target prediction task. Our results indicate that the herein reported models have considerable potential to identify small molecules with epigenetic activity. Therefore, our results were implemented as freely accessible and easy-to-use web application.</p>

Big data investments in knowledge and non-knowledge intensive firms: what the market tells us

2017 ◽  
Vol 21 (3) ◽  
pp. 623-639 ◽  
Author(s):  
Tingting Zhang ◽  
William Yu Chung Wang ◽  
David J. Pauleen
Keyword(s):  
Big Data ◽  
Knowledge Management ◽  
Stock Market ◽  
Value Chain ◽  
Stock Prices ◽  
Economic Value ◽  
Information Value ◽  
Publicly Traded ◽  
Content Type ◽  
Knowledge Intensive

Purpose This paper aims to investigate the value of big data investments by examining the market reaction to company announcements of big data investments and tests the effect for firms that are either knowledge intensive or not. Design/methodology/approach This study is based on an event study using data from two stock markets in China. Findings The stock market sees an overall index increase in stock prices when announcements of big data investments are revealed by grouping all the listed firms included in the sample. Increased stock prices are also the case for non-knowledge intensive firms. However, the stock market does not seem to react to big data investment announcements by testing the knowledge intensive firms along. Research limitations/implications This study contributes to the literature on assessing the economic value of big data investments from the perspective of big data information value chain by taking an unexpected change in stock price as the measure of the financial performance of the investment and by comparing market reactions between knowledge intensive firms and non-knowledge intensive firms. Findings of this study can be used to refine practitioners’ understanding of the economic value of big data investments to different firms and provide guidance to their future investments in knowledge management to maximize the benefits along the big data information value chain. However, findings of study should be interpreted carefully when applying them to companies that are not publicly traded on the stock market or listed on other financial markets. Originality/value Based on the concept of big data information value chain, this study advances research on the economic value of big data investments. Taking the perspective of stock market investors, this study investigates how the stock market reacts to big data investments by comparing the reactions to knowledge-intensive firms and non-knowledge-intensive firms. The results may be particularly interesting to those publicly traded companies that have not previously invested in knowledge management systems. The findings imply that stock investors tend to believe that big data investment could possibly increase the future returns for non-knowledge-intensive firms.

scholarly journals iPSC technology-based regenerative medicine for kidney diseases

2021 ◽  
Author(s):  
Kenji Osafune
Keyword(s):  
Regenerative Medicine ◽  
Cell Therapy ◽  
Kidney Development ◽  
Disease Modeling ◽  
Kidney Diseases ◽  
Collecting Duct ◽  
Current Status ◽  
Renal Tubules ◽  
Discovery Research ◽  
Drug Discovery Research

AbstractWith few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct organoids. Furthermore, human kidney tissues can be generated from these hiPSC-derived progenitors, in which NPC-derived glomeruli and renal tubules and UB-derived collecting ducts are interconnected. The induced kidney tissues are further vascularized when transplanted into immunodeficient mice. In addition to the kidney reconstruction for use in transplantation, it has been demonstrated that cell therapy using hiPSC-derived NPCs ameliorates acute kidney injury (AKI) in mice. Disease modeling and drug discovery research using disease-specific hiPSCs has also been vigorously conducted for intractable kidney disorders, such as autosomal dominant polycystic kidney disease (ADPKD). In an attempt to address the complications associated with kidney diseases, hiPSC-derived erythropoietin (EPO)-producing cells were successfully generated to discover drugs and develop cell therapy for renal anemia. This review summarizes the current status and future perspectives of developmental biology of kidney and iPSC technology-based regenerative medicine for kidney diseases.

Synthetic Strategies to Access Heteroatomic Spirocentres Embedded in Natural Products

Synthesis ◽  
2021 ◽  
Author(s):  
Michael P. Badart ◽  
Bill C. Hawkins
Keyword(s):  
Natural Products ◽  
Heterocyclic Compound ◽  
Chemical Space ◽  
Three Dimensional ◽  
Coupling Reactions ◽  
Conjugate Additions ◽  
Biological Targets ◽  
Compound Libraries ◽  
The Common ◽  
Significant Attention

AbstractThe spirocyclic motif is abundant in natural products and provides an ideal three-dimensional template to interact with biological targets. With significant attention historically expended on the synthesis of flat-heterocyclic compound libraries, methods to access the less-explored three-dimensional medicinal-chemical space will continue to increase in demand. Herein, we highlight by reaction class the common strategies used to construct the spirocyclic centres embedded in a series of well-studied natural products.1 Introduction2 Cycloadditions3 Palladium-Catalysed Coupling Reactions4 Conjugate Additions5 Imines, Aminals, and Hemiaminal Ethers6 Mannich-Type Reactions7 Oxidative Dearomatisation8 Alkylation9 Organometallic Additions10 Conclusions

scholarly journals Recent Advances in Discovery of Lead Structures from Microbial Natural Products: Genomics- and Metabolomics-Guided Acceleration

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2542
Author(s):  
Linda Sukmarini
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Screening Methods ◽  
Technological Advancement ◽  
Natural Origin ◽  
Drug Discovery And Development ◽  
New Methodologies ◽  
Analytical Instrumentation ◽  
Microbial Natural Products ◽  
Drug Leads

Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. They offer major opportunities for finding novel lead structures that are active against a broad spectrum of assay targets, particularly those from secondary metabolites of microbial origin. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques. Aided by the more in-depth understanding of different biosynthetic pathways and the technological advancement in analytical instrumentation, the development of new methodologies provides an alternative that can accelerate discoveries of new lead-structures of natural origin. This present mini-review briefly discusses selected examples regarding advancements in bioinformatics and genomics (focusing on genome mining and metagenomics approaches), as well as bioanalytics (mass-spectrometry) towards the microbial NPs-based drug discovery and development. The selected recent discoveries from 2015 to 2020 are featured herein.

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