Pharmamedia and pectinase production by Bacillus subtilis Mz-12P.

Bacterial isolates collected from the environment were screened for pectinolytic activity, and a strain with the highest activity was selected and identified as Bacillus subtilis Mz-12. The presence of pectin hydrolase, lyase, and esterase activities was confirmed. Pectinase was purified and characterized. Enzyme production was optimized with respect to temperature, pH, and growth medium. Enzyme stability and activity were characterized under different temperatures and pH values. The results showed that this strain was capable of producing high yields of pectinase in commercial medium (Pharmamedia) 24.6 U/mL compared to other media. The purified pectinase of 22.3 kDa produced was constitutive in nature. The isolated enzyme from this strain displayed a wide range of temperature and pH stability, with the optimal activity observed at pH 9.0 and 50°C. These results indicate that the B. subtilis Mz-12 strain is a favorable candidate for industrial enzyme production. The use of Pharmamedia is reported for first time for pectinase production.

Formation of 5-Aminomethyl-2,3-dihydropyridine-4(1H)-ones from 4-Amino-tetrahydropyridinylidene Salts.

Various 4-aminotetrahydropyridinylidene salts were treated with aldehydes in an alkaline medium. Their conversion to 5-substituted ß-hydroxyketones in a one-step reaction succeeded only with an aliphatic aldehyde. Instead, aromatic aldehydes gave 5-substituted ß-aminoketones or a single δ-diketone. The new compounds were characterized using spectroscopic methods and a single crystal structure analysis. Some of them showed anticancer and antibacterial properties.

Review of Marine Cyanobacteria and the Aspects Related to Their Roles: Chemical, Biological Properties, Nitrogen Fixation and Climate Change.

Marine cyanobacteria are an ancient group of photosynthetic microbes dating back to 3.5 million years ago. They are prolific producers of bioactive secondary metabolites. Over millions of years, natural selection has optimized their metabolites to possess activities impacting various biological targets. This paper discusses the historical and existential records of cyanobacteria, and their role in understanding the evolution of marine cyanobacteria through the ages. Recent advancements have focused on isolating and screening bioactive compounds and their respective medicinal properties, and we also discuss chemical property space and clinical trials, where compounds with potential pharmacological effects, such as cytotoxicity, anticancer, and antiparasitic properties, are highlighted. The data have shown that about 43% of the compounds investigated have cytotoxic effects, and around 8% have anti-trypanosome activity. We discussed the role of different marine cyanobacteria groups in fixing nitrogen percentages on Earth and their outcomes in fish productivity by entering food webs and enhancing productivity in different agricultural and ecological fields. The role of marine cyanobacteria in the carbon cycle and their outcomes in improving the efficiency of photosynthetic CO2 fixation in the chloroplasts of crop plants, thus enhancing the crop plant's yield, was highlighted. Ultimately, climate changes have a significant impact on marine cyanobacteria where the temperature rises, and CO2 improves the cyanobacterial nitrogen fixation.

Determination of Hypoglycemic, Hypolipidemic and Nephroprotective Effects of Berberis Calliobotrys in Alloxan-Induced Diabetic Rats.

Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and Berberis calliobotrys has been found to be an inhibitor of α-glucosidase, α-amylase and tyrosinase. Thus, this study investigated the hypoglycemic effects of Berberis calliobotrys methanol extract/fractions using in vitro and In vivo methods. Bovine serum albumin (BSA), BSA-methylglyoxal and BSA-glucose methods were used to assess anti-glycation activity in vitro, while in vivo hypoglycemic effects were determined by oral glucose tolerance test (OGTT). Moreover, the hypolipidemic and nephroprotective effects were studied and phenolics were detected using high performance liquid chromatography (HPLC). In vitro anti-glycation showed a significant reduction in glycated end-products formation at 1, 0.25 and 0.5 mg/mL. In vivo hypoglycemic effects were tested at 200, 400 and 600 mg/kg by measuring blood glucose, insulin, hemoglobin (Hb) and HbA1c. The synergistic effect of extract/fractions (600 mg/kg) with insulin exhibited a pronounced glucose reduction in alloxan diabetic rats. The oral glucose tolerance test (OGTT) demonstrated a decline in glucose concentration. Moreover, extract/fractions (600 mg/kg) exhibited an improved lipid profile, increased Hb, HbA1c levels and body weight for 30 days. Furthermore, diabetic animals significantly exhibited an upsurge in total protein, albumin and globulin levels, along with a significant improvement in urea and creatinine after extract/fractions administration for 42 days. Phytochemistry revealed alkaloids, tannins, glycosides, flavonoids, phenols, terpenoids and saponins. HPLC showed the presence of phenolics in ethyl acetate fraction that could be accountable for pharmacological actions. Therefore, it can be concluded that Berberis calliobotrys possesses strong hypoglycemic, hypolipidemic and nephroprotective effects, and could be a potential therapeutic agent for diabetes treatment.

Characterization of subtilosin gene in wild type Bacillus spp. and possible physiological role.

In a designed study to screen for antimicrobial exhibiting bacteria using molecular aspects, Bacillus species were considered to investigate antibiotic biosynthesis genes. 28 bacterial strains and 3 induced mutants were screened for the presence of subtilosin gene (sbo) and subtilosin through PCR and Mass spectrometry respectively. Sbo gene was detected in 16 out of 28 Bacillus strains. The results from gene sequences deliberated by multiple sequence alignments revealed high-level homology to the sequences of the sbo-alb gene locus of B. subtilis 168 and the other limited reported strains. Hence, this report provided additional strains to support the idea of subtilosin gene predominance amongst Bacillus strains isolated from environment and to find different species containing homologous genes, furthermore the utilization of its conserved region as a means of identifying Bacillus spp. that produce subtilosin. This is the first report to confirm the detection of subtilosin production from B. amyloliquefaciens.

The Chemical Property Position of Bedaquiline Construed by a Chemical Global Positioning System-Natural Product.

Bedaquiline is a novel adenosine triphosphate synthase inhibitor anti-tuberculosis drug. Bedaquiline belongs to the class of diarylquinolines, which are antituberculosis drugs that are quite different mechanistically from quinolines and flouroquinolines. The fact that relatively similar chemical drugs produce different mechanisms of action is still not widely understood. To enhance discrimination in favor of bedaquiline, a new approach using eight-score principal component analysis (PCA), provided by a ChemGPS-NP model, is proposed. PCA scores were calculated based on 35 + 1 different physicochemical properties and demonstrated clear differences when compared with other quinolines. The ChemGPS-NP model provided an exceptional 100 compounds nearest to bedaquiline from antituberculosis screening sets (with a cumulative Euclidian distance of 196.83), compared with the different 2Dsimilarity provided by Tanimoto methods (extended connective fingerprints and the Molecular ACCess System, showing 30% and 182% increases in cumulative Euclidian distance, respectively). Potentially similar compounds from publicly available antituberculosis compounds and Maybridge sets, based on bedaquiline's eight-dimensional similarity and different filtrations, were identified too.

Preparation of new 1,3-dibenzyl tetrahydropyridinylidene ammonium salts and their antimicrobial and anticellular activities.

New 1,3 dibenzyl -tetrahydropyridinylidene ammonium salts have been prepared from unsubstituted or N-benzylated tetrahydropyridinylidene ammonium salts. The antiplasmodial and antitrypanosomal activities as well as their cytotoxic effects were determined using microplate assays. In addition, their activities against two gram positive and two gram negative bacteria strains and a yeast strain were examined. Furthermore, anticancer effects against two cell lines were investigated. Physicochemical parameters were calculated and structure-activity-relationships discussed. One compound showed antiplasmodial activity against a multiresistant strain of Plasmodium falciparum in subnanomolar concentration. Antitrypanosomal activities were detected in low nanomolar concentrations. A single compound was active against grampositive and gramnegative bacteria, as well as yeast. One compound inhibited the growth of a HCT cell line in low concentration.

Evaluating Antimycobacterial Screening Schemes Using Chemical Global Positioning System-Natural Product Analysis.

Most of the targeted discoveries in tuberculosis research have covered previously explored chemical structures but neglected physiochemical properties. Until now, no efficient prediction tools have been developed to discriminate the novelty of screened compounds at early stages. To overcome this deficit, a drastic novel approach must include physicochemical properties filters provided by Chemical Global Positioning System-Natural Product analysis (ChemGPS-NP). Three different screening schemes GSK, GVKBio, and NIAID provided 776, 2880, and 3779 compounds respectively and were evaluated based on their physicochemical properties and thereby proposed as deduction examples. Charting the physiochemical property spaces of these sets identified the merits and demerits of each screening scheme by simply observing the distribution over the chemical property space. We found that GSK screening set was confined to a certain space, losing potentially active compounds when compared with an in-house constructed 459 highly active compounds (active set), while the GVKBio and NIAID screening schemes were evenly distributed through space. The latter two sets had the advantage, as they have covered a larger space and presented compounds with additional variety of properties and activities. The in-house active set was cross-validated with MycPermCheck and SmartsFilter to be able to identify priority compounds. The model demonstrated undiscovered spaces when matched with Maybridge drug-like space, providing further potential targets. These undiscovered spaces should be considered in any future investigations. We have included the most active compounds along with permeability and toxicity filters as supplemented material.

Marine Natural Products: A Source of Novel Anticancer Drugs.

Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.

Cardenolides: Insights from chemical structure and pharmacological utility.

Cardiac glycosides (CGs) are a class of naturally occurring steroid-like compounds, and members of this class have been in clinical use for more than 1500 years. They have been used in folk medicine as arrow poisons, abortifacients, heart tonics, emetics, and diuretics as well as in other applications. The major use of CGs today is based on their ability to inhibit the membrane-bound Na+/K+-ATPase enzyme, and they are regarded as an effective treatment for congestive heart failure (CHF), cardiac arrhythmia and atrial fibrillation. Furthermore, increasing evidence has indicated the potential cytotoxic effects of CGs against various types of cancer. In this review, we highlight some of the structural features of this class of natural products that are crucial for their efficacy, some methods of isolating these compounds from natural resources, and the structural elucidation tools that have been used. We also describe their physicochemical properties and several modern biotechnological approaches for preparing CGs that do not require plant sources.

Synthesis of new 1-benzyl tetrahydropyridinylidene ammonium salts and their antimicrobial and anticellular activities.

A series of N-benzyl tetrahydropiperidinylidene pyrrolidinium salts have been synthesized and investigated for their antiplasmodial and antitrypanosomal activities as well as for their cytotoxic effects. The antibacterial, antimycobacterial and anticancer potencies of selected compounds were examined, too. Physicochemical parameters were calculated and structure-activity-relationships are discussed.

Purification of Bioactive Lipopeptides Produced by Bacillus subtilis Strain BIA.

Bacillus subtilis strain BIA was used for the production of bioactive lipopeptides. Different extraction and purification methods were assayed as liquid-liquid extraction, and acid and ammonium sulfate precipitation followed by TLC, SPE, and gel filtration. Active fractions were further purified using RP-HPLC. The molecular mass of the purified product from HPLC was determined through Tris-Tricine SDS-PAGE and MALDI-TOF-MS. The results revealed that Bacillus subtilis strain BIA produced surfactin and iturin like compounds. Coproduction of surfactin and iturin like compounds by this strain is a remarkable trait for a potential biocontrol agent. This paper also includeds techniques that have been developed for the optimal and convenient extraction of bioactive lipopeptides from microbial origin.