Sandeep Dhankhar

Investigations Towards New Antidiabetic Drugs from Fungal Endophytes Associated with Salvadora Oleoides Decne

The nature has provided abundant natural resources which can be explored for their medicinal uses. The present study was undertaken to investigate the antidiabetic and hypolipidemic activity of various extracts fractions obtained from mycelia of seventeen endophytic fungi in different solvents (methanol, acetone and aqueous) isolated from Salvadora oleoides Decne (Salvadoraceae) in glucose loaded fasting and alloxan induced diabetic Wistar albino rats. Only four extracts namely; unidentified fungus (aqueous), Aspergillus sp.JPY2 (methanol), Aspergillus sp.JPY1 (methanol) and Phoma sp. (acetone) significantly reduced blood glucose levels as revealed by glucose tolerance test. It has been observed that in alloxan induced diabetic rats, the maximum reduction in blood glucose level was after 5 hours in the acute treatment experiment and on14th day in sub acute treatment at a dose of 250mg/kg of body weight (P<0.05). The reduction in blood glucose in long term treatment experiment was ranged from 11.3% to 28.04%, whereas standard drug tolbutamide reduced the blood glucose level up to 40%. In long term treatment, unidentified fungus (aqueous) extract showed significant improvement in parameters like body weight and lipid profile of alloxan induced diabetic rats. The gas chromatography mass spectrometer (GCMS) analysis of bioactive fraction (aqueous) of unidentified fungus and methanolic extract fraction of Aspergillus sp.JPY1 revealed that the main constituents were 2, 6-di-tert-butyl-p-cresol and Phenol, 2, 6-bis (1, 1-dimethylethyl)-4-methyl respectively. The results have also suggested that the above four bioactive fractions have good margin of safety and did not show any lethal effects on the animals up to the doses of 1000mg/kg b.w. along with safe doses up to 500 μg/ ml to human erythrocytes.

Analysis Toward Innovative Herbal Antibacterial & Antifungal Drugs

The antimicrobial activities of four medicinal plants Argemona mexicana, Achyranthes aspera, Catharanthus roseus, and Syzygium cumini were evaluated against Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae, Proteus vulgaris, Bacillus subtilis, Salmonella typhi and three Aspergillus species. Extracts from Achyranthes aspera and Catharanthus roseus showed the highest antimicrobial potential (MIC 0.375-0.750 mg/ml) while extract from Argemona mexicana and Syzygium cumini, showed less activity. In disc diffusion assay, only eight out of twenty extracts showed antimicrobial activity at a concentration of 25.0 μg/ disc. The GCMS investigation reveals the existence of 2-bornanone; 1, 2-benzenedicarboxylic acid, bis (2-methylpropyl) ester; hexadecanoic acid, methyl ester and hexatriacontane in water extract fraction of C. roseus. The present research article provides a review of some medicinal plants incorporating antimicrobial drugs, together with recent advances in emerging therapeutics in clinical development and related patents for exploitation of herbal medicine.

Construction of 3D homochiral metal–organic frameworks (MOFs) of Cd(II): selective CO2 adsorption and catalytic properties for the Knoevenagel and Henry reaction

Two new homochiral metal–organic frameworks of Cd(II), [{Cd2(L-glu)2(bpe)3(H2O)}·2H2O] (1) and [{Cd3(L-glu)2(bpe)3(H2O)}·2NO3·H2O] (2) (where, L-glu = L-glutamate dianion, and bpe = 1,2-bis(4-pyridyl)ethylene) have been synthesized solvothermally by employing two different temperatures. Single crystal X-ray diffraction studies revealed that both 1 and 2 are homochiral and possess a 3D pillar-layered framework structure having 4,8- and 8,10-connected binodal nets with vertex symbols of {3^2.4.5^3}{3^4.4^6.5^10.6^8} and {3^11.4^28.5^5.6}2{3^8.4^18.5.6}, respectively. Interestingly, solvothermal synthesis carried out at 100 °C resulted in a 3D framework, 1 which features large rectangular 1D channels with a dimension of ∼10.38 × 4.44 A2 decorated with pendant –NH2 groups. Whereas, increasing the temperature of the reaction to 120 °C led to a non-porous highly connected 3D framework, 2 in which the –NH2 group of the L-glu ligand is coordinated to a Cd(II) node. Gas (N2, CO2, H2 and Ar) uptake studies on the dehydrated framework of 1 revealed excellent selectivity for CO2 over other gases at 273 K with a high isosteric heat of adsorption (Qst) value of 40.8 kJ mol−1. The high selectivity for CO2 gas has been attributed to the stronger interaction of CO2 with the basic –NH2 functionalized pore surface of compound 1. Furthermore, 1 acts as a very good recyclable catalyst for the carbon–carbon bond forming reactions, such as the Knoevenagel condensation and Henry reaction of benzaldehydes. Moreover, the catalyst can be easily separated from the reaction mixture and reused in four consecutive cycles without significant loss of catalytic activity and structural rigidity.

Genomics of Chronic Obstructive Pulmonary Disease (COPD); Exploring the SNPs of Protease-Antiprotease Pathway

The COPD has been an important respiratory condition that affects people worldwide and its incidence has been alarming. The increasing incidence of this disorder has been attributed to global industrialization and environmental pollution. Although the exposures to environmental pollutants and smoking have been important triggers, the genetic component of individuals has been shown to be important for development and progression of COPD. Recent literature reported that protease-antiprotease imbalance to be important in etiopathogenesis of COPD. The enzymes namely neutrophil elastase and matrix metalloprotienases are considered to be foremost proteolytic molecules released by neutrophils and macrophages during inflammatory events in COPD. Normally, the lungs remain protected from the destructive effect of these two antiproteases by α1-antitrypsin (α1AT) and tissue inhibitors of metalloproteinases (TIMPs) respectively. In this review, we are trying to highlight the work by various research groups in exploring the SNPs of various genes of inflammatory pathways and the protease-antiprotease pathway, which may have some degree of association with COPD.

Green synthesis, optical and magnetic properties of a MnII metal–organic framework (MOF) that exhibits high heat of H2 adsorption

Green synthesis of a 3D, Mn(II) metal–organic framework (MOF) composed of a trimeric Mn(II) cluster and NDC linker formulated as [Mn3(NDC)3(DMA)4]n (1) (where, NDC = 2,6 napthalene dicarboxylic acid, DMA = N,N-dimethylacetamide) has been achieved by employing mechanochemical and sonochemical routes. Interestingly, MOF 1 undergoes reversible structural transformation upon desolvation and solvation of DMA molecules. The desolvated framework, 1′ containing two unsaturated Mn(II) sites exhibits interesting H2 and CO2 uptake properties with isosteric heats of adsorption (Qst) for H2 and CO2 of 11.8 and 29.2 kJ mol−1, respectively. Remarkably, the Qst of H2 estimated for 1′ is found to be the highest value amongst the Mn(II) MOFs reported so far and the high value has been attributed to the stronger interaction of H2 with the unsaturated Mn(II) centers. Further, variable temperature magnetic susceptibility measurements of 1 revealed weak antiferromagnetic coupling interactions between the adjacent Mn(II) ions. The thermal stability of 1 has also been examined and was found to be highly stable. Photoluminescence investigation revealed that the emission from MOF 1 is owed to ligand based charge transfer transitions. Furthermore, compound 1 undergoes temperature induced solid-state conversion into phase pure MnO nanocrystals of about 10–18 nm in size embedded in a carbonaceous layer to form MnO–C nanocomposite (NC). The MnO–C NC has been characterized by PXRD, FE-SEM, EDAX and TEM analyses.

Investigating Antimicrobial Properties of Endophytic fungi Associated with Salvadora oleoides Decne

Virtually all fungal endophytes produce a variety of bioactive molecule, which is currently attracting worldwide scientific attention towards isolation and exploration of their biotechnological promise. In the present study, 17 endophytic fungi (identified by way of morphological and/or sequence based molecular methods) were screened for antimicrobial activity against pathogenic strains of six bacteria and three Aspergilli sp. The seventeen culturable fungi extracted with three solvents in increasing polarity; acetone, methanol and water were examined for antimicrobial activity in crude extracts using microbroth dilution assay. Tetracycline and Amphotericin B were used as positive controls against different bacterial strains and Aspergilli respectively. The crude extracts of Aspergillus sp. JPY1, Aspergillus sp. JPY2, Aspergillus niger and an unidentified sp. exhibited the maximum activity against three pathogenic Aspergilli sp. Their in vitro minimum inhibitory concentrations (MICs) against Aspergilli were found to be 0.387-12.50 mg/ml by microbroth dilution. In disc diffusion assay, only eleven out of fifty-one fungal extracts were found to be endowed with antimicrobial activity at a preset concentration of 50 μg/ disc which could be the potential source to develop new antimicrobial agents. The work on study of cytotoxicity and phytochemical screening (preliminary and GC-MS) of crude extracts endowed with antimicrobial properties is reported here. It is the first report of Salvadora oleoides associated endophytic fungi with antimicrobial activity, which could be an essential source of bioactive compounds useful for developing better antifungal or antibacterial drugs with good therapeutic index value.

Advancement in Infection Control of Opportunistic Pathogen (Aspergillus spp.): Adjunctive Agents

There is continuous emergence of resistant strains which leads to urgent need to discover new antifungal agents. The investigation of adjunctive agents for antifungal activity might help to optimize the therapy for Invasive Aspergillosis (IA). The chelating agents Ethylenediamine Tetraacetic Acid (EDTA) & Disodium salt of EDTA (DiEDTA) as adjunct to antifungal drugs have been investigated against 8 pathogenic isolates of Aspergillus spp. The MIC (Minimum Inhibitory Concentration) found by DDA (Disc Diffusion Assay) is 7.50-15.0 μg/disc; by MDA (Microbroth Dilution Assay) is 30.0-49.13 μg/ml & SGIA (Spore germination Inhibition Assay) is 30.0-49.13 μg/ml. Moreover, these agents did not show any toxicity up to a concentration of 312.5 μg/ml. The antifungal activity is also confirmed by another method i.e time kill curve analysis. While these agents were ten times less active than gold standard drug (Amphotericin B; AmpB) but eight times less toxic than AmpB. This leads to preliminary investigation of in vitro combination of chelating agents with antifungal drugs (Polyenes & Azoles) by DDA. These combinations showed a significant increase in zone of inhibition in contrast to single drug used. This preliminary work with chelating agents suggest that EDTA as an enhancing agent with antifungal properties in combination with antifungal drugs can be used in pharmaceutical preparations. Further investigation is in progress.

Safety and Efficacy of Green Foliage in the Treatment of Fungal Infections and Associated Clinical Conditions

Forty five crude extracts of nine selected medicinal plants, based on their use in respiratory and other disorders in traditional systems of medicine were analyzed for their potential activity against three pathogenic species of Aspergillus. The presence of phenols, tannins, flavanoids, terpenoid, steroids, alkaloids and saponins in the different extracts was established. The crude extracts were examined for antifungal activity in concentration ranging from 5000.0 to 19.53 µg/ml using microbroth dilution assay in which twenty two extracts exhibited the anti-Aspergilli activity. The petroleum ether extract of Justicia adhatoda and water extract of Commelina bengalensis exhibited the maximum activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. Their in vitro minimum inhibitory concentrations (MICs) were found to be 156.0-312.0 µg/ml by microbroth dilution and spore germination inhibition assays. In disc diffusion assay, at concentration of 10 µg/disc of some crude extracts showed significant activity against Aspergilli. The toxicity (in vitro and in vivo) of bio-active fractions was evaluated, in which the extracts isolated from J. adhatoda were found to be non-toxic. Gas chromatography-mass spectrometry (GCMS) studies were performed for various extracts (petroleum ether, chloroform and acetone) of J. adhatoda which resulted in the identification of several bioactive compounds. The antifungal activity along with acute toxicity, cyto-toxicity as well as genotoxicity of extract fractions from J. adhatoda justifies the use of such screening in the expedition for new drugs.

Invasive aspergillosis: adjunctive combination therapy

Invasive aspergillosis remains a serious opportunistic fungal infection particularly in patients with a reduced immune defense such as those with hematological malignancies or transplant recipients. The mortality of invasive infections due to Aspergillus spp. is still high. The main reasons for this are the difficulty in diagnosing of these infections and the limited efficacy of antifungal agents. There is no optimal therapy for invasive aspergillosis, and therefore many clinicians have attempted to utilize a combination approach to improve outcomes. The current antifungal classes of drugs targeting the cell wall and cell membrane may need adjunctive agents focused on separate cellular pathways that can be used in combination therapy to maximize the efficacy, a valuable alternative to the monotherapy. The endeavor of this article is to review the literature on combination therapy by using adjunctive agents against Aspergillus spp and assess its eventual usability in the treatment of invasive aspergillosis.

Fine tuning through valence bond tautomerization of ancillary ligands in ruthenium(II) arene complexes for better anticancer activity and enzyme inhibition properties

Four new ruthenium arene PTA type complexes have been synthesized using substituted picolinamide derivatives as ancillary ligands and characterized by spectroscopic methods. In one of the complexes, the ancillary ligand has shown an unprecedented valence-bond tautomerization in the presence of an ammonium salt to act as a polar neutral donor ligand making the ligand more prone towards substitution. The same compound has shown remarkable antiproliferative activity against three cancer cell lines with GI50 values comparable to Adriamycin, a known therapeutic drug. Along with this it also strongly inhibits the action of thioredoxin reductase, which might be a probable reason for the enhanced proliferative action of the valence-bond tautomerized compound.