Bioactive Extracts: Strategies to generate Diversified Natural Product Like Libraries

Natural products have stimulated chemists owing to their abundant structural diversity and complexity. Indeed, natural products have performed an essential role, particularly in the cure of cancerous and infectious diseases, thereby posing medicinal researchers with a scope of unexplored chemotypes for the innovation of new drugs. Fusion of chemical derivatization and combinatorial synthesis forms the basis of the concept of chemo diversification of plants. Diverse libraries of natural product analogs are constructed through existing biological and chemical approaches using unique schemes to expand natural product frameworks. This review aims to present several approaches employed to offer innovative opportunities to synthesize NP-inspired compound libraries. Reactive molecular fragments present in most natural products are chemically converted to chemically engineered extracts (CEEs) or semisynthetic compounds constituting distinct libraries. Bio-guided isolation for natural products required vital tools like reverse phase chromatography and bioautographic assays. Different established strategies from DTS, BIOS, CtD, FOS, FBDD to Late-stage diversification facilitate the expansion of molecules with physicochemical properties. In particular, fragment-like natural products with novel skeletons may be used as preliminary points for chemical biology and medicinal chemistry programs with great capacity. In this review, we sum up how NPs have proven fruitful for the novel methodologies responsible for the diversification of complex natural products; thereby, it is worthy of going over the upcoming integration of natural products with combinatorial chemistry.

Ethnomedicinal uses, phytochemistry, pharmacology, and toxicity of the genus Nymphaea L.: A review.

Background: Plants from the genus Nymphaea L. have been used for decades to treat various diseases, including dysentery, diarrhea, uterine cancer, gonorrhea, inflammation conditions, among others. The present study aims to critically analyze comprehensive literature on ethnopharmacological uses, phytochemistry, pharmacology, and toxicity of Nymphaea L. Methods: The available information on Nymphaea L. was obtained from textbooks, theses, as well as published articles through libraries, and electronic databases. Results: More than 150 compounds, including flavonoids, phenolics, alkaloids, miscellaneous compounds, etc. were identified from Nymphaea L. extracts and pure molecules from Nymphaea L. exhibited a wide range of pharmacological activities, including antimicrobial, anti-inflammatory, anticancer, immunomodulatory, hepatoprotective, antioxidant, cytotoxic, among others. Conclusion: Referring to in vitro and in vivo studies, Nymphaea sp. are very promising medicinal plants, however, more in vivo experiments, cytotoxicity tests, and detailed mechanisms of action of their extracts, and compounds are recommended to confirm their ethnomedicinal claims into scientific rationale-based information.

Chalcone-thiosemicarbazone Hybrids as Inhibitors of Human Hepatocellular Carcinoma HepG2 Cells Viability and Oxygen Consumption

Background: Chalcones are open-chain flavonoids especially attractive to medicinal chemistry due to their easy synthesis and the possibility of structural modifications. Objective: Evaluate the in vitro anticancer activity of a series of hybrids chalcones-thiosemicarbazones against the human hepatocellular carcinoma cell line, HepG2. Methods: Seven hybrid chalcones-thiosemicarbazones (CTs), 3-(4’-X-phenyl)-1-phenylprop-2-en-1-one thiosemicarbazone, where X=H (CT-H), CH3 (CT-CH3), NO2 (CT-NO2), Cl (CT-Cl), CN (CT-CN), F (CT-F) and Br (CT-Br), were synthesized and their effects on cells viability and mitochondrial oxygen consumption were accessed. Results: Incubation with CTs caused a decrease in HepG2 cells viability in a time-concentration-dependent manner. The most effective compounds in inhibiting cell viability, after 24 hours of treatment, were CT-Cl and CT-CH3 (IC50 20.9 and 23.63 μM, respectively). In addition, using 10 M and only 1 hour of pre-incubation, CT-CH3 caused a reduction in basal respiration (-37%), oxygen consumption coupled with ATP synthesis (-60%) and maximum oxygen consumption (-54%). These alterations in respiratory parameters may be involved with the inhibitory effects of CT-CH3, since significant changes in oxygen consumption rates were observed in a condition that anticipates more significant losses of cell viability. The ADME parameters and the no violation of Lipinski Rule of Five showed that all compounds are safe. Conclusion: These results may contribute to the knowledge about the effects of CTs on these cells and the development of new treatments against HCCs.

Can the incorporation of different concentrations of buriti (Mauritia flexuosa) oil change the rheological properties of filmogenic solutions? A factorial experimental design approach

Background: Buriti (Mauritia flexuosa) oil has high economic potential because it contains monounsaturated and polyunsaturated fatty acids with high antioxidant potential and high carotenoid content, making it an excellent source of pro-vitamin A. Objective: The objective of this work was to evaluate the rheological properties of filmogenic solutions incorporated with different buriti oil concentrations. Methods: Buriti oil (0.15 to 0.45 % w/v) and emulsifier (Tween®20) (0.02 to 0.04 % w/v) were combined using a factorial experimental design 22 with 3 central points for the preparation of filmogenic solutions with cassava starch (3%, w/v) and glycerol (0.06%, w/v). Rheological properties, static and centrifugation emulsion stabilities, and pH value of filmogenic solutions were evaluated. Results: Filmogenic solutions with lower emulsifier concentration showed increased flow resistance and non-Newtonian and pseudoplastic behavior (n<1). Central point formulation (E, F, and G) remained stable (no particle agglomeration) throughout the test period as well as pH value close to neutrality. In centrifugation stability index at 3500 rpm, only formulation C did not show phase separation. Conclusion: It was possible to develop a mixture of a filmogenic solution containing buriti oil that could be applied as an eco-friendly coating in food.

Synthesis, Biological Screening and Docking Study of Some Novel Pyrazolopyrano[2,3-B]quinolin Derivatives as Potent Antibacterial Agents

Background: Pyranopyrazoles have a variety of biological activities and can be obtained by various starting materials and synthetic methods. Also, pyrazolopyrano[2,3-b]quinolins that contain pyranopyrazole moiety, have some biological activities such as anti acetylcholinesterase, anti butyrylcholinesterase activity. In this research, our objective is to prepare pyranopyrazole compounds and pyrazolopyrano[2,3-b]quinolins in a simple way and then evaluate their antibacterial effect. Methods: In this study, pyrano[2,3-c]pyrazole derivatives have been synthesized by condensing malononitrile, aromatic aldehydes, and 3-methyl-1-phenyl-2-pyrazolin-5-one in the presence of magnesium perchlorate as a catalyst. Then we prepared pyrazolopyrano[2,3-b]quinolins via subsequent Friedlander reaction between cyclohexanone and the obtained pyrano[2,3-c]pyrazoles. Also, the antimicrobial activity of the synthesized pyrazolopyrano[2,3-b]quinolins against Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli were measured. Then we studied molecular docking of them to find the predicted compounds' interactions and binding energy with DNA-gyrase with the AutoDock 4.2 software. Results: Pyrazolopyrano[2,3-b]quinolins were synthesized in optimized conditions. Evaluation of their antibacterial activities showed that these compounds have moderate to good antibacterial activities against four bacteria species. Also molecular docking tests of docked compounds showed a strong bonding interaction with DNA-Gyrase and had been docked into the intercalation place of DNA of DNA-gyrase complex. The molecule bounded to the DNA stabilized by the H bonds, hydrophobic interactions, and π-π interaction. Conclusion: We have developed an efficient and one-pot ecofriendly protocol for the synthesis of some novel pyrano[2,3-c]pyrazol derivatives and pyrazolopyrano[2,3-b]quinolins under simple conditions and then tested them for their antibacterial activities. Also, we studied molecular docking of them. These compounds showed moderate to good inhibitory action.

Kolaviron, a Biflavonoid Compound: Pharmacological activity and Therapeutic Efficacy

The use of herbal remedies for medicinal purposes is becoming more popular around the world. As a result, plants have become viable treatment options for a variety of diseases. Garcinia kola (bitter kola) is a perennially grown plant in the Guttiferae family that has been evaluated and reported to have numerous health-promoting properties. Kolaviron is a biflavanoid and major phytochemical found in Garcinia kola that includes Garcinia Biflavanoid-1 (GB-1), kolaflavanone, and Garcinia Biflavanoid-2 (GB-2). It is obtained as a fraction extracted from Garcinia kola. Kolaviron's pharmacological properties include anti-inflammatory, anti-spasmodic, ameliorative, anti-asthmatic, anti-cancer, anti-malarial, hepatoprotective, antioxidant, anti-atherogenic, neuroprotective, anti-diabetic, and anti-amnesic properties. Kolaviron is recommended for use in clinical settings because it has been shown to have a high therapeutic efficacy in clinical trials. The purpose of this review is to assess the therapeutic efficacy of kolaviron.

Phytoconstituents of Lantana camara L.: Rekindling Hope in the Cancer Treatment

Background: Lantana camara L. belongs to the family Verbenaceae. It originated in Tropical America in Southern Georgia and to the North of Texas and was introduced in Calcutta, India in the year 1809 as an ornamental hedge. The plant L. Camara is also distributed in Southeast Asia, China, Australia, Brazil, West Indies, Kenya, Mexico, East Africa, Tanzania. Many of its phytoconstituents possess medicinal properties which are used traditionally to treat fever, uterine hemorrhage, and excess menstrual discharge, chronic ulcers, rheumatism, gonorrhea, toothache, gastrointestinal pain, etc, and has been used in Brazil for curing malaria, mange, headaches, colds, and fevers. Objectives: The review elaborates traditional practices, phytochemistry of Lantana camara L. along with the role of Lantana camara in various types of cancers. Method: The data on L. camara was collected through different online databases like Web of Science, PubMed, Science Direct, Springer, and Google Scholar. Results: Major phytoconstituents isolated from the plant shows anticancer activity specially lantadene A-D, icterogenin, oleanolic acid, lantacamaric acid A, B, oleanonic acid, etc. In vitro and in vivo studies demonstrate its potential for various cancers. Certain extracts, isolated compounds, and their semi-synthetic derivatives have depicted a significant cytotoxic and anti-proliferative effect. Conclusion: Clinical studies are not yet established, therefore, making it crucial to direct future researches in that area.

A review on bioactive constituents of essential oils as mosquito repellent

Currently, the research focus has been on finding new alternatives to synthetic mosquito repellents due to their toxicity. Natural products act as a suitable alternative since plant-based mosquito repellents have been used traditionally due to their low toxicity. Essential oils as mosquito repellent have gained importance due to various functional bioactive constituents. Different formulations of essential oils have been studied from time to time to enhance the stability and protection time. However, the underlying mechanism of repellent activity of the bioactive constituents against specific mosquito species remains unexplored. This review focuses on the various sources of essential oil with their bioactive components and their receptor-based mechanism of action for inducing mosquito repellency against different mosquito species. Furthermore, a comparison of the various formulations of essential oil-based mosquito repellents with synthetic repellents has been discussed.