scholarly journals The Search for Putative Hits in Combating Leishmaniasis: The Contributions of Natural Products Over the Last Decade

Author(s):  
Patrick O. Sakyi ◽  
Richard K. Amewu ◽  
Robert N. O. A. Devine ◽  
Emahi Ismaila ◽  
Whelton A. Miller ◽  
...  

Abstract Despite advancements in the areas of omics and chemoinformatics, potent novel biotherapeutic molecules with new modes of actions are needed for leishmaniasis. The socioeconomic burden of leishmaniasis remains alarming in endemic regions. Currently, reports from existing endemic areas such as Nepal, Iran, Brazil, India, Sudan and Afghanistan, as well as newly affected countries such as Peru, Bolivia and Somalia indicate concerns of chemoresistance to the classical antimonial treatment. As a result, effective antileishmanial agents which are safe and affordable are urgently needed. Natural products from both flora and fauna have contributed immensely to chemotherapeutics and serve as vital sources of new chemical agents. This review focuses on a systematic cross-sectional view of all characterized anti-leishmanial compounds from natural sources over the last decade. Furthermore, IC50/EC50, cytotoxicity and suggested mechanisms of action of some of these natural products are provided. The natural product classification includes alkaloids, terpenes, terpenoids, and phenolics. The plethora of reported mechanisms involve calcium channel inhibition, immunomodulation and apoptosis. Making available enriched data pertaining to bioactivity and mechanisms of natural products complement current efforts geared towards unraveling potent leishmanicides of therapeutic relevance. Graphic Abstract

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 349
Author(s):  
Asim Najmi ◽  
Sadique A. Javed ◽  
Mohammed Al Bratty ◽  
Hassan A. Alhazmi

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.


2013 ◽  
Vol 16 (2) ◽  
pp. 123
Author(s):  
Basil D Roufogalis ◽  
Arthur D Conigrave ◽  
Emanuel E Strehler

This Special Issue of the Journal of Pharmacy and Pharmaceutical Sciences arises from an inaugural conference on “Mechanism-Based Natural Product Development” held at Whistler Mountain, Canada on September 21-22, 2012. The aim of the conference was to bring together scientists from various disciplines to discuss the development of new therapeutic products from natural medicines based on mechanistic and related scientific studies. It provided an opportunity to explore new directions in natural medicine research and development, with the ultimate objective of leading to greater integration of natural and conventional synthetic pharmaceutical medicines for the health of the community worldwide. The concept for this conference and the Special Issue has come from the growing interest internationally in traditional and natural medicinal health products in recent years. It may, at first, appear surprising that developed countries are re-embracing natural product research and development. There are of course many reasons for this, including growing community interest in natural products providing improved health and wellbeing, the growing difficulty and cost of maintaining a pipeline of effective and, above all, safe new products for chronic diseases in the mainstream pharmaceutical industry, and the knowledge that many of our small drug pharmaceutical medicines have come from plants and other organisms. But as traditional natural product medicines increasingly enter the mainstream, the call for evidence to support their use also grows louder. Essential to the acceptance of natural medicines are the validation of their traditional uses and identification, isolation and structural characterization of their active components, together with the elucidation of their mechanisms of biological action, adverse effects, and identification of their molecular targets. These requirements provide the focus of this Special Issue. Scientific investigation and development of new health products requires the joining together of many disciplines, including chemistry, pharmacology, pharmacognosy and cell and molecular biology, as well as integration with clinical medicine. Natural product medicines are expected to be multi-component and multi-targeted. Are they effective, safe and properly standardized in their existing formulations? Are there opportunities to isolate single active components for standardization and conventional drug discovery and development? Answering these questions requires collaboration between scientific disciplines focused on a common goal. In line with the aims of the conference, the Special Issue has incorporated review and original research articles related to mechanisms of action in a number of therapeutic areas, mostly from invited speakers at the Whistler conference. Other articles were unsolicited submissions to the Journal that satisfy the scope of the issue. Articles range from reports on efforts to work with traditional owners in the appropriate cultural context, to develop new therapeutics based on traditional literature, to discover new medicinal products, to develop new pharmaceuticals based on the isolation of active chemical components, to develop new methods of delivery, and to identify mechanisms of action. The medical 'territory' includes cancer, heart disease, diabetes and related chronic inflammatory diseases, pain pathways, deafness and infertility. Other articles investigate the quality and safety of products by the application of current analytical methods, the potential for interactions of natural products (e.g., cranberry) with pharmaceutical medicines and the variability of a selection of similar natural product medicines with regard to their contents of therapeutically beneficial and marker compounds, as claimed on the product labels. In addition, the issue includes the abstracts of posters that formed an important part of the conference, especially from postgraduate students and postdoctoral fellows. These are included as Proceedings. We are indebted to the scientists who willingly gave their time and resources to attend the Whistler conference and, in many cases, submitted manuscripts for inclusion in this Special Issue. The delegates and contributors came from many places, near and far, to make this inaugural conference on mechanism-based natural product development a success. Such a conference and the subsequent proceedings in the Special issue are not possible without the work of many. We thank the organizing and scientific committee for their support and valuable suggestions. A conference of this scope would not be possible without sponsorship; this includes especially the National Health Products Research Society of Canada, the Canadian Society for Pharmaceutical Sciences and several Universities. Major support, without program or editorial input, was provided by SOHO Flordis International (SFI). We commend them for believing in the quest for clinically proven and research-based products based on an understanding of underlying mechanisms. The support of Purapharm International is also gratefully acknowledged. We would like to dedicate this Special Issue to Professor Allan SY Lau of the University of Hong Kong, who contributed enthusiastically to the organization of the conference and its program, but was ultimately unable to attend due to his untimely passing. Professor Lau was a pioneer in the integration of natural and orthodox medical studies and his inspiration will be greatly missed. Basil D Roufogalis, Arthur D Conigrave and Emanuel E Strehler Co-Guest Editors


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hyun Woo Kim ◽  
Seong Yeon Choi ◽  
Hyeon Seok Jang ◽  
Byeol Ryu ◽  
Sang Hyun Sung ◽  
...  

AbstractMany natural product chemists are working to identify a wide variety of novel secondary metabolites from natural materials and are eager to avoid repeatedly discovering known compounds. Here, we developed liquid chromatography/mass spectrometry (LC/MS) data-processing protocols for assessing high-throughput spectral data from natural sources and scoring the novelty of unknown metabolites from natural products. This approach automatically produces representative MS spectra (RMSs) corresponding to single secondary metabolites in natural sources. In this study, we used the RMSs of Agrimonia pilosa roots and aerial parts as models to reveal the structural similarities of their secondary metabolites and identify novel compounds, as well as isolation of three types of nine new compounds including three pilosanidin- and four pilosanol-type molecules and two 3-hydroxy-3-methylglutaryl (HMG)-conjugated chromones. Furthermore, we devised a new scoring system, the Fresh Compound Index (FCI), which grades the novelty of single secondary metabolites from a natural material using an in-house database constructed from 466 representative medicinal plants from East Asian countries. We expect that the FCIs of RMSs in a sample will help natural product chemists to discover other compounds of interest with similar chemical scaffolds or novel compounds and will provide insights relevant to the structural diversity and novelty of secondary metabolites in natural products.


Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 49
Author(s):  
Alejandro M. S. Mayer ◽  
Aimee J. Guerrero ◽  
Abimael D. Rodríguez ◽  
Orazio Taglialatela-Scafati ◽  
Fumiaki Nakamura ◽  
...  

The review of the 2016–2017 marine pharmacology literature was prepared in a manner similar as the 10 prior reviews of this series. Preclinical marine pharmacology research during 2016–2017 assessed 313 marine compounds with novel pharmacology reported by a growing number of investigators from 54 countries. The peer-reviewed literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral activities for 123 marine natural products, 111 marine compounds with antidiabetic and anti-inflammatory activities as well as affecting the immune and nervous system, while in contrast 79 marine compounds displayed miscellaneous mechanisms of action which upon further investigation may contribute to several pharmacological classes. Therefore, in 2016–2017, the preclinical marine natural product pharmacology pipeline generated both novel pharmacology as well as potentially new lead compounds for the growing clinical marine pharmaceutical pipeline, and thus sustained with its contributions the global research for novel and effective therapeutic strategies for multiple disease categories.


2015 ◽  
Vol 32 (8) ◽  
pp. 1249-1266 ◽  
Author(s):  
Milla Kibble ◽  
Niina Saarinen ◽  
Jing Tang ◽  
Krister Wennerberg ◽  
Sari Mäkelä ◽  
...  

This article reviews key network pharmacology concepts and recent experimental–computational approaches that have been successfully applied to natural product research, including unbiased elucidation of mechanisms of action and systematic prediction of effective therapeutic combinations.


2018 ◽  
Author(s):  
Jonathan J. Mills ◽  
Kaylib R. Robinson ◽  
Troy E. Zehnder ◽  
Joshua G. Pierce

The lipoxazolidinone family of marine natural products, with an unusual 4-oxazolidinone heterocycle at their core, represents a new scaffold for antimicrobial discovery; however, questions regarding their mechanism of action and high lipophilicity have likely slowed follow-up studies. Herein, we report the first synthesis of lipoxazolidinone A, 15 structural analogs to explore its active pharmacophore, and initial resistance and mechanism of action studies. These results suggest that 4-oxazolidinones are valuable scaffolds for antimicrobial development and reveal simplified lead compounds for further optimization.


2018 ◽  
Author(s):  
William A. Shirley ◽  
Brian P. Kelley ◽  
Yohann Potier ◽  
John H. Koschwanez ◽  
Robert Bruccoleri ◽  
...  

This pre-print explores ensemble modeling of natural product targets to match chemical structures to precursors found in large open-source gene cluster repository antiSMASH. Commentary on method, effectiveness, and limitations are enclosed. All structures are public domain molecules and have been reviewed for release.


2020 ◽  
Vol 17 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Ghodsi Mohammadi Ziarani ◽  
Fatemeh Mohajer ◽  
Zohreh kheilkordi

Background: Natural products have been received attention due to their importance in human life as those are biologically active. In this review, there are some reports through different methods related to the synthesis of the indolizidine 195B which was extracted from poisonous frog; however, due to respect nature, the synthesis of natural compounds such as indolizidine has been attracted much attention among scientists and researchers. Objective: This review discloses the procedures and methods to provide indolizidine 195B from 1989 to 2018 due to their importance as a natural product. Conclusion: There are several methods to give rise to the indolizidine 195B as a natural product that is highly active from the biological perspective in pharmaceutical chemistry. In summary, many protocols for the preparations of indolizidine 195B from various substrates, several reagents, and conditions have been reported from different aromatic and aliphatic.


2021 ◽  
Author(s):  
Nengzhong Wang ◽  
Zugen Wu ◽  
Junjie Wang ◽  
Nisar Ullah ◽  
Yixin Lu

A comprehensive and updated summary of asymmetric organocatalytic annulation reactions is presented; in particular, the applications of these annulation strategies to natural products synthesis are highlighted.


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