Natural Products Journal, The - Volume 7, Issue 2, 2017

Natural drugs have become a subject of world importance with both therapeutic and economic implications. Natural products are harnessed as potential therapeutic candidates from natural resources for the discovery of lead drug candidates and new pharmaceutical products. The natural products provide most of the FDA approved formulations. Thus, they are the continuous source of inspiration in the development of new drug candidates. Naturally derived products have the significant role to treat life-threatening conditions. Information collected from various database sources such as Pubmed, Scopus, ScienceDirect, Google Scholar etc. has revealed that biologically important scaffold and molecules are abundantly naturally available. Hence, the information is compiled as a short review on some highly valuable natural resources as anti-infective agents. Moreover, a special emphasis has also been laid on the marine anti-infective agents. This compilation will pave way for scientific, academic and industrial researchers to look forward to discover high valued anti-infective agents.

Schinus areira L. (syn. Schinus molle L. var. areira (L.) DC.) belongs to the Anacardiaceae family, native to South America, now widely distributed in temperate zones of the world, known as “aguaribay”, “árbol de la pimienta”, “pepper tree”, “terebinto” or “pimentero”. It is considered a medicinal plant in the folk medicine and it is also appreciated by its culinary properties. Its fruits are used as a spice and to prepare a popular drink named “chicha”. These popular uses have stimulated a number of biological and chemical studies. This communication offers a general view of the structural characteristics of the secondary metabolites isolated from S. areira L., as well as their ethnomedicinal uses, biological activities and toxicological considerations.

Background: Medicinal phytochemicals have been used as dietary supplements in Asia and Africa for thousands of years. Biologically active antioxidants are very diverse and low in their chemical compositions thereby limiting their efficacies. The present study focuses on the enhanced accumulation of closely related dietary antioxidants: shikimate, quinate, salicylate and tocopherol in Phyla dulcis, the Central American herb known for its anti-inflammatory medicinal properties; but its polyphenolic antioxidants had not been studied. Methods: Phyla dulcis stem cuttings were planted in the greenhouse, and in field plots and treated with solutions of stoichiometric mixes of mineral salts known to double crop biomass and yield. Controls were treated with water. At maturity, P. dulcis shoots and flowers were harvested per treatment, immediately frozen in liquid nitrogen, and submitted to metabolomic analyses by gas chromatography-time-of-flight mass spectrometry. Results: Field plot P. dulcis treated with KKS-mineral salts combination induced increased shikimate accumulation of 1.59 g per 100 g from the 0.799 g per 100 g in the untreated control. Similarly salicylate, quinate, and tocopherols increased in accumulation by many orders of magnitude in the stoichiometric mixes of mineral salts-treated P. dulcis compared with the untreated controls. Conclusion: The accumulated polyphenolic antioxidants permitted the deduction of the unique biosynthetic pathway of the shikimate, with a massive inhibition at the enzyme steps of dehydroquinate dehydratase and shikimate dehydrogenase.

Background: Indole-3-Acetic Acid (IAA) is a plant hormone with various applications in the field of agriculture, medicine and research. Objective: We herein examined the production of IAA from various cyanobacterial strains. Method: During the present work, 34 cyanobacterial strains were screened to check their ability toexcrete IAA. Culture conditions of the strain producing maximum IAA content under normal conditions, were manipulated to check their effect on IAA production. Excreted IAA was characterized by Thin-Layer Chromatography (TLC), Gas Chromatography-Mass Spectroscopy (GC-MS) and Fourier Transform Infrared Spectroscopy (FTIR). Results: IAA was detected in 20 of the total strains screened. Cylindrospermum stagnale showed maximum IAA production (95.6 μg/ml) in comparison to other strains studied. During optimization experiments, highest IAA content was observed when C. stagnale was incubated with 1,500 μg/mL L-tryptophan, 0.5 μg/mL EDTA, 9 μg/mL citric acid and 1 μg/mL NaCl in BG-11 media at the pH 7.5 for 3 days. Conclusion: This work intends to 1) search an agriculturally significant cyanobacterial strain which excretes highest amount of IAA among the studied strains; 2) to understand the culture conditions favoring IAA secretion by this strain; and 3) to validate the excreted substance to be IAA through various techniques.

Background: Forskolin, a polyhydroxylated labdone diterpene extracted from Coleus forskohlii possesses various medicinal properties and has been used in the treatment of number of chronic diseases, in humans. Objectives: The effects of forskolin and its analogues (1a-1f) on COX-2 enzyme activity were evaluated (in silico and in vitro studies). Materials and Methods: Forskolin and its analogues (1a-1f) were evaluated for their interactions with COX-2 protein by using Auto Dock Vina software and visualized using pyMOL. Forskolin and its analogues 1b and 1e were further tested in vitro against human recombinant COX-2 enzyme for their effects in various concentrations (50, 75, 100, 150, 200 nM). Celecoxib was used as a reference standard for comparison in both in silico and in vitro studies Results: The in silico studies revealed that forskolin analogue (1b) exhibited highest binding score of -9.8 K cal mol-1 and formation of hydrogen bonds with Arg120, Glu524 and Ser530 amino acid residues, similar to celecoxib. The in vitro studies revealed that the tested compounds (forskolin, 1b, 1e and celecoxib) inhibited COX-2 enzyme activity in a concentration dependent manner and the IC50 value for forskolin, 1b, 1e and celecoxib were found to be 123 nM, 75.2 nM, 84.8 nM and 90.2 nM respectively. Conclusion: This is the first report on the evaluation of effects of forskolin and its analogues (1b and 1e) on COX-2 enzyme specifically to substantiate their anti-inflammatory potentials.

Background: Plants, including herbs and spices, have many phytochemicals which are a potential source of natural antioxidants e.g., phenolic diterpenes, flavonoids, alkaloids, tannins and phenolic acids. Various researches have been done to find out the relative antioxidant activities of various herbs, fruits, vegetables and spices. Objectives: Present study was carried out to evaluate the antioxidant status of five common spices namely Brassica nigra (Rai), Foeniculum vulgare (Fennel), Carum copticum (Ajwain), Nigella sativa (Kalonji) and Sesamum indicum (Til). Methodology: In-vitro antioxidant study of these spices was examined by using the popular method of DPPH free radical scavenging activity and FRAP methods. The total phenolic compounds were measured using the Folin-Ciocalteu reagent in an effort to validate the medicinal potential of the spices. Results: The antioxidant activity of the methanolic extract of Brassica nigra (92.8%) was observed to be the highest followed by Foeniculum vulgare (91.8%), Carum copticum (89.7%), Nigella sativa (83.2%) while for Sesamum indicum, least antioxidant activity was recorded (38%). Their IC50 ranged from 4 mg/ml in Brassica nigra (Rai) to 8 mg/ml in Nigella sativa (Kalonji). Nitric oxide scavenging activity was highest in Rai (11%) and lowest in Til. The ferric reducing properties of the above spices were also found to be quite appreciable. Highest phenolic content (based on Folin's Ciocalteau method) was shown by Carum copticum (18.1) whereas highest flavonoid content was recorded in Foeniculum vulgare (20.7). Conclusion: The significant presence of phenolic and flavonoid content revealed that the spices can be used as rich sources of natural antioxidants against various oxidative stress related disorders.

Background: Visceral Leishmaniasis (VL) is a fatal disseminated protozoan infection. VL threatens 200 million people in 62 countries and responsible for 40,000 deaths each year. Chemotherapy is the only tool for the treatment of VL, but, as yet, none of the available drugs are ideal for treatment due to high toxicity, resistance issues and prohibitive prices. Hence, there is an urgent need for the development of new and safer drugs. Methods: In view of this, a series of 7-trifluoromethyl-4-aminoquinoline derivatives were synthesized and evaluated for in vitro and in vivo antileishmanial activity against promastigote as well as amastigote forms of Leishmania donovani. Results: All the analogues displayed 81-99% inhibition of promastigotes at 10 μM concentration. Most of the analogues exhibited good in vitro antiamastigote activity (IC50 = 5.3 - 9.6 μM) compared to reference compounds, chloroquine (15.3 μM) and miltefosine (8.1 μM). The compounds exhibiting antiamastigote activity in vitro were further tested for in vivo efficacy in Leishmania donovani/hamster model. Amongst all, compound 6c showed 76.02 ± 13.60% inhibition of Leishmania parasite in treated animals as compared to infected untreated hamsters on day 27 post infection. Conclusion: The present results indicate the potential of aminoquinoline scaffold for further optimization.

Background: In Kenya, several species of the genus Maytenus are used in traditional medicine to treat many diseases including malaria. In this study, phytochemical constituents and extracts of Maytenus undata, M. putterlickioides, M. senegalensis and M. heterophylla were evaluated to determine compound/s responsible for antimalarial activity. Objective: To isolate antiplasmodial compounds from these plant species which could be used marker compounds in the standardization of their extracts as a phytomedicine for malaria. Methods: Constituents were isolated through activity-guided fractionation of the MeOH/CHCl3 (1:1) extracts and in vitro inhibition of Plasmodium falciparum. Cytotoxicity was evaluated using Vero cells and the compounds were elucidated on the basis of NMR spectroscopy. Results: Fractionation of the extracts resulted in the isolation of ten known compounds. Compound 1 showed promising antiplasmodial activity with IC50, 3.63 and 3.95 ng/ml against chloroquine sensitive (D6) and resistant (W2) P. falciparum, respectively and moderate cytotoxicity (CC50, 37.5 ng/ml) against Vero E6 cells. The other compounds showed weak antiplasmodial (IC50 >1.93 μg/ml) and cytotoxic (CC50 > 39.52 μ g/ml) activities against P. falciparum and Vero E6 cells, respectively. Conclusion: (20α)-3-hydroxy-2-oxo-24-nor-friedela-1(10),3,5,7-tetraen-carboxylic acid-(29)-methylester (pristimerin) (1) was the most active marker and lead compound that warrants further investigation as a template for the development of new antimalarial drugs. Pristimerin is reported for the first time in M. putterlickioides. 3-Hydroxyolean-12-en-28-oic acid (oleanolic acid) (5), stigmast-5-en-3-ol (β-sitosterol) (6), 3-oxo-28-friedelanoic acid (7), olean-12-en-3-ol (β-amyrin) (8), lup-20(29)-en-3-ol (lupeol) (9) and lup-20(29)-en-3-one (lupenone) (10) are reported for the first time in M. undata.

Background: Spirulina spp., a promising source of phycocyanin, is commercially grown in open ponds and raceways photoautotrophically. However, the economic exploitation in an open system seems to have been limited because of lack of multiple stress-tolerant strains. Methods: In order to have an improved production of phycocyanin, a NaCl tolerant mutant of the cyanobacterium Spirulina platensis was isolated using a chemical mutagen, N-methyl-N'-nitro-Nnitrosoguanidine (NTG) and selection for NaCl tolerant strain. Results: The mutant strain exhibited improved growth and overproduced phycocyanin at 0.8 M NaCl. NaCl-tolerant mutant also exhibited higher rate of photosynthesis and reduced rate of respiration in response to 0.8 M NaCl. The mutant strain took up more nitrate and reduced it more effectively in presence of NaCl which explains its enhanced phycocyanin accumulatory behavior. The mutant strain also protected its cells from NaCl stress by ccumulating low amounts of trehalose, glucosyl-glycerol and proline, and by synthesizing anti-oxidative enzymes in comparison to wild type strain which further supports the subdued effects of NaCl and halotolerant behavior of mutant strain. Conclusion: The NaCl tolerant mutant synthesized 1.5 folds higher phycocyanin as compared to wild type in response to 0.8 M NaCl. The mutant strain clearly demonstrates unique haloprotective strategies that mitigate the deleterious effects of high NaCl concentration as reflected by its efficient photosynthesis and nitrogen metabolism. Moreover, the subdued defense response of mutant in relation to osmolytes accumulation and antioxidant enzymes confirms its adaptive and tolerant behavior against NaCl.