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The search for new Natural Products is one of the oldest interests for research in chemistry. The history of this discipline is very prolific, from its initial uses as medicine to advanced omics strategies to understand the mechanics of biological controls in living cells. The discoveries of morphine, penicillin, taxol and many other natural products revolutionized human health. During the last 40 years, excellent reviews published by Dr. David Newman and Dr. Gordon Crag have revealed that the pharmaceutical industry's research into natural products has lost some of its steam. Nevertheless, new natural products for antimicrobials, antifungals, and anticancer drugs remained the main alternative. Furthermore, research institutes have seen great vigor, and several startup companies have emerged worldwide, seeking therapeutic alternatives based in natural products. Innovations on spectrometric hardware, allowing broader coverage of chemical classes and spatial mapping, and in software, enabling the interpretation of large volumes of data, afforded a renewed interest in natural products and are considered the most important enabling technology for the new companies. In this perspective article we give some historical context to exciting developments, on software and spatial resolution, that promise to pave the way for a bright future of Natural Products research. [ABSTRACT FROM AUTHOR]

The importance of Xenorhabdus and Photorhabdus symbionts to their respective Steinernema and Heterorhabditis nematode hosts is that they not only contribute to their entomopathogenicity but also to their fecundity through the production of small molecules. Thus, this mini-review gives a brief introductory overview of these nematophilic bacteria. Specifically, their type species, nematode hosts, and geographic region of isolations are tabulated. The use of nucleotide sequence-based techniques for their species delineation and how pangenomes can improve this are highlighted. Using the Steinernema-Xenorhabdus association as an example, the bacteriumnematode lifecycle is visualized with an emphasis on the role of bacterial biomolecules. Those currently in drug development are discussed, and two potential antimalarial lead compounds are highlighted. Thus, this minireview tabulates forty-eight significant nematophilic bacteria and visualizes the ecological importance of their biomolecules. It further discusses three of these biomolecules that are currently in drug development. Through it, one is introduced to Xenorhabdus and Photorhabdus bacteria, their natural production of biomolecules in the nematode-bacterium lifecycle, and how these molecules are useful in developing novel therapies. [ABSTRACT FROM AUTHOR]

Black walnut (Juglans nigra) is considered one of the most valuable plants, with a global production of 3.5 million tons of dried fruit yearly. Throughout the past two millennia, its allelopathic effects have been widely recognized. Black walnuts produce a natural naphthoquinone called juglone, which occurs naturally in all parts of the tree, particularly the green husk, and contributes significantly to the allelopathic effects of black walnut. Except for the fruit’s edible nature, the walnut green husk (Pericarpium Juglandis) has been used for centuries to make wine, natural dyes, and traditional medicines to cure certain diseases. Within the extracts of walnut green husk, 1,4-naphthoquinones, gallic acid, caffeic acid, and quercitrin were separated and characterized. Among these compounds, the major active ingredient with a good application prospect is juglone, which has proven to be a natural chemical compound with anticancer, antitumor, antibacterial, and antiviral activities, especially the strong anticancer activity. Juglone is also an environmentally friendly biological pesticide and herbicide. Certainly, the environmental impact of juglone also needs to be considered. Significant quantities of walnut green husk are currently produced as a byproduct of walnut production; however, its value has not been fully utilized and explored, which raises environmental concerns. This review attempts to: 1) summarize the origin and historical use of walnut and walnut green husk; 2) introduce the structure, biosynthesis pathway, extraction method, biological activity, and potential applications of juglone, as well as its environmental impact assessment.

The importance of Xenorhabdus and Photorhabdus symbionts to their respective Steinernema and Heterorhabditis nematode hosts is that they not only contribute to their entomopathogenicity but also to their fecundity through the production of small molecules. Thus, this mini-review gives a brief introductory overview of these nematophilic bacteria. Specifically, their type species, nematode hosts, and geographic region of isolations are tabulated. The use of nucleotide sequence-based techniques for their species delineation and how pangenomes can improve this are highlighted. Using the Steinernema–Xenorhabdus association as an example, the bacterium-nematode lifecycle is visualized with an emphasis on the role of bacterial biomolecules. Those currently in drug development are discussed, and two potential antimalarial lead compounds are highlighted. Thus, this mini-review tabulates forty-eight significant nematophilic bacteria and visualizes the ecological importance of their biomolecules. It further discusses three of these biomolecules that are currently in drug development. Through it, one is introduced to Xenorhabdus and Photorhabdus bacteria, their natural production of biomolecules in the nematode-bacterium lifecycle, and how these molecules are useful in developing novel therapies.

Cuminum cyminum L (Family: Apiaceae) is a small multipurpose herb. Seeds of cumin are widely used as a spice for its distinctive aroma, and more commonly in various indigenous traditional systems of medicine. Access through web literature provides ample evidence for biomedical activities of Cuminum cyminum seeds (CCS). CCS has been used in traditional medicine to treat variety of diseases, including hypolipidemia, cancer, and diabetes. Biomedical properties of CCS is attributed to its phytochemical class of compounds viz., terpenes, phenols and flavonoids. Health effects of CCS have been experimentally validated through phytochemical screening deciphering the fact that it contains a large number of bioactive secondary metabolites (BASMs) viz., alkaloid, coumarin, anthraquinones, flavonoid, glycoside, protein, resin, saponin, tannin and steroid. Furthermore, pharmacological studies indicate that BASMs in CCS exert antimicrobial, insecticidal, anti-inflammatory, analgesic, antioxidant, anticancer, antidiabetic, anti-platelet-aggregation, hypotensive, bronchodilatory, immunological, contraceptive, anti-amyloidogenic, anti-osteoporotic, aldose reductase, α-glucosidase and tyrosinase inhibitory effects. Cuminaldehyde is one of the major bioactive compounds in CCS that holds significant pharmacological prominence. However, in-depth studies are lacking henceforth warranted to elucidate and fill the gaps, particularly on phytocompound isolation, pre-clinical, clinical characterization, and evaluation of structure–activity relationship. The present study prospects ADMETox perspectives of cuminaldehyde (4-Isopropylbenzaldehyde). [ABSTRACT FROM AUTHOR]

Abstract Computer-aided research on the relationship between molecular structures of natural compounds (NC) and their biological activities have been carried out extensively because the molecular structures of new drug candidates are usually analogous to or derived from the molecular structures of NC. In order to express the relationship physically realistically using a computer, it is essential to have a molecular descriptor set that can adequately represent the characteristics of the molecular structures belonging to the NC’s chemical space. Although several topological descriptors have been developed to describe the physical, chemical, and biological properties of organic molecules, especially synthetic compounds, and have been widely used for drug discovery researches, these descriptors have limitations in expressing NC-specific molecular structures. To overcome this, we developed a novel molecular fingerprint, called Natural Compound Molecular Fingerprints (NC-MFP), for explaining NC structures related to biological activities and for applying the same for the natural product (NP)-based drug development. NC-MFP was developed to reflect the structural characteristics of NCs and the commonly used NP classification system. NC-MFP is a scaffold-based molecular fingerprint method comprising scaffolds, scaffold-fragment connection points (SFCP), and fragments. The scaffolds of the NC-MFP have a hierarchical structure. In this study, we introduce 16 structural classes of NPs in the Dictionary of Natural Product database (DNP), and the hierarchical scaffolds of each class were calculated using the Bemis and Murko (BM) method. The scaffold library in NC-MFP comprises 676 scaffolds. To compare how well the NC-MFP represents the structural features of NCs compared to the molecular fingerprints that have been widely used for organic molecular representation, two kinds of binary classification tasks were performed. Task I is a binary classification of the NCs in commercially available library DB into a NC or synthetic compound. Task II is classifying whether NCs with inhibitory activity in seven biological target proteins are active or inactive. Two tasks were developed with some molecular fingerprints, including NC-MFP, using the 1-nearest neighbor (1-NN) method. The performance of task I showed that NC-MFP is a practical molecular fingerprint to classify NC structures from the data set compared with other molecular fingerprints. Performance of task II with NC-MFP outperformed compared with other molecular fingerprints, suggesting that the NC-MFP is useful to explain NC structures related to biological activities. In conclusion, NC-MFP is a robust molecular fingerprint in classifying NC structures and explaining the biological activities of NC structures. Therefore, we suggest NC-MFP as a potent molecular descriptor of the virtual screening of NC for natural product-based drug development.

Insufficient assessment of the identity and chemical composition of complex natural products, including botanicals, herbal remedies, and dietary supplements, hinders reproducible research and limits understanding mechanism(s) of action and health outcomes, which in turn impede improvements in clinical practice and advances in public health. This review describes available analytical resources and good methodological practices that support natural product characterization and strengthen the knowledge gained for designing and interpreting safety and efficacy investigations. The practice of validating analytical methods demonstrates that measurements of constituents of interest are reproducible and appropriate for the sample (e.g., plant material, phytochemical extract, and biological specimen). In particular, the utilization of matrix-based reference materials enables researchers to assess the accuracy, precision, and sensitivity of analytical measurements of natural product constituents, including dietary ingredients and their metabolites. Select case studies are presented where the careful application of these resources and practices has enhanced experimental rigor and benefited research on dietary supplement health effects.

Computer-aided research on the relationship between molecular structures of natural compounds (NC) and their biological activities have been carried out extensively because the molecular structures of new drug candidates are usually analogous to or derived from the molecular structures of NC. In order to express the relationship physically realistically using a computer, it is essential to have a molecular descriptor set that can adequately represent the characteristics of the molecular structures belonging to the NC's chemical space. Although several topological descriptors have been developed to describe the physical, chemical, and biological properties of organic molecules, especially synthetic compounds, and have been widely used for drug discovery researches, these descriptors have limitations in expressing NC-specific molecular structures. To overcome this, we developed a novel molecular fingerprint, called Natural Compound Molecular Fingerprints (NC-MFP), for explaining NC structures related to biological activities and for applying the same for the natural product (NP)-based drug development. NC-MFP was developed to reflect the structural characteristics of NCs and the commonly used NP classification system. NC-MFP is a scaffold-based molecular fingerprint method comprising scaffolds, scaffold-fragment connection points (SFCP), and fragments. The scaffolds of the NC-MFP have a hierarchical structure. In this study, we introduce 16 structural classes of NPs in the Dictionary of Natural Product database (DNP), and the hierarchical scaffolds of each class were calculated using the Bemis and Murko (BM) method. The scaffold library in NC-MFP comprises 676 scaffolds. To compare how well the NC-MFP represents the structural features of NCs compared to the molecular fingerprints that have been widely used for organic molecular representation, two kinds of binary classification tasks were performed. Task I is a binary classification of the NCs in commercially available library DB into a NC or synthetic compound. Task II is classifying whether NCs with inhibitory activity in seven biological target proteins are active or inactive. Two tasks were developed with some molecular fingerprints, including NC-MFP, using the 1-nearest neighbor (1-NN) method. The performance of task I showed that NC-MFP is a practical molecular fingerprint to classify NC structures from the data set compared with other molecular fingerprints. Performance of task II with NC-MFP outperformed compared with other molecular fingerprints, suggesting that the NC-MFP is useful to explain NC structures related to biological activities. In conclusion, NC-MFP is a robust molecular fingerprint in classifying NC structures and explaining the biological activities of NC structures. Therefore, we suggest NC-MFP as a potent molecular descriptor of the virtual screening of NC for natural product-based drug development. [ABSTRACT FROM AUTHOR]

Highlights: [•] The PIDP was established to pursue target-based insecticide discovery. [•] Screens identified agonists and antagonists of mosquito and tick DARs. [•] “Hit-to-lead” studies identified AaDOP2 antagonists as next-gen insecticide leads. [•] TM domains of mosquito and tick DARs share 73-100% amino acid identity. [•] Invertebrate DARs have potential for target-based insecticide discovery. [ABSTRACT FROM AUTHOR]

Insufficient assessment of the identity and chemical composition of complex natural products, including botanicals, herbal remedies, and dietary supplements, hinders reproducible research and limits understanding mechanism(s) of action and health outcomes, which in turn impede improvements in clinical practice and advances in public health. This review describes available analytical resources and good methodological practices that support natural product characterization and strengthen the knowledge gained for designing and interpreting safety and efficacy investigations. The practice of validating analytical methods demonstrates that measurements of constituents of interest are reproducible and appropriate for the sample (e.g., plant material, phytochemical extract, and biological specimen). In particular, the utilization of matrix-based reference materials enables researchers to assess the accuracy, precision, and sensitivity of analytical measurements of natural product constituents, including dietary ingredients and their metabolites. Select case studies are presented where the careful application of these resources and practices has enhanced experimental rigor and benefited research on dietary supplement health effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hosbas Coskun, Wise and Kuszak.)