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Bovine pancreatic trypsin was crystallized, in-complex with Lima bean trypsin inhibitor (LBTI) (Phaseolus lunatus L.), in the form of a ternary complex. LBTI is a Bowman-Birk-type bifunctional serine protease inhibitor, which has two independent inhibitory loops. Both of the loops can inhibit trypsin, however, only the hydrophobic loop is specific for inhibiting chymotrypsin. The structure of trypsin incomplex with the LBTI has been solved and refined at 2.25 Å resolution, in the space group P4

Natural products based novel crown ethers have been prepared by employing biologically active natural structures including tetrahydroisoquinoline, chrysin and biochanin-A as the side arms. The resulting crown scaffolds were evaluated for their anticancer potential against two cancer cell lines i.e. NCI-H460 (non-small lung carcinoma), MCF-7 (breast adenocarcinoma). The comparative study showed that the addition of crown scaffold put marked effects on antiproliferative profile of parent natural precursors and is significant for lung carcinoma in particular. Biochanin-A derived crown ether showed three (03) folds higher antiproliferative activity (IC50 = 6.08 ± 0.07 µM) against lung carcinoma as compared to standard drug cisplatin (IC50 = 19.00 ± 1.24 µM). Cytotoxic trends for NIH-3T3 cell lines were also examined and found reduced as compared to parent natural structures. Hence, these findings could open a new pathway towards developing effective carcinostatic drugs.HIGHLIGHTSFour natural products based novel crown ethers have been developed.Comparative antiproliferative screening of crown ethers and natural precursors.Addition of crown showed marked effects on anticancer profile of natural products.Crown formation is significant for lung carcinoma potential in particular.Biochanin-A derived crown ether found three folds more active than standard drug.

Bu yazıda Dr. Shoaib Ahmad Malik, ""Islam and Evolution: Al-Ghazālī and the Modern Evolutionary Paradigm" adlı eserini yazmasına neden olan amaç ve motivasyonlara ilişkin açıklamalar yapmaktadır., Dear editor of KADER. I am writing this letter both to congratulate you on your first issue to be published in English and to give you information about my new book called Islam and Evolution: Al-Ghazālī and the Modern Evolutionary Paradigm. It is the first book written from an Islamic perspective that is published with Routledge’s Science and Religion series. More specifically, it analyses the discussion of evolution through the lens of Islamic scholastic theology (kalām). I know that KADER occupies a very important space in kalām in Turkey, and it is why I hope you will find this to be a helpful addition in your first issue in English, which I hope will globally contribute to the studies in İslamic thought in general and the field of kalām in particular.

Neglected tropical diseases hinder social and economic growth in many tropical areas. We report leishmanicidal activities of isoflavanquinones and antifungal potentials of fractions from methanol root extract of Abrus precatorius. Agar dilution method was used to determine antifungal properties while 96-well dilution protocol was adopted for antileishmanial activities. Ethyl acetate fraction of A. precatorius root extract showed moderate activity against M. canis and F. solani with percentage inhibition of 42.5% and 55.0% respectively while other fractions were inactive. Crude extract, n-hexane, and ethyl acetate fractions demonstrated potent antileishmanial activities with IC50 values of 22.20 ± 0.540 μg/mL, 19.35 ± 0.670 μg/mL, and 6.32 ± 0.001 μg/mL respectively, against L. major. The ethyl acetate fraction, which was the most active fraction, was subjected to successive column chromatography followed by preparative recycling HPLC in order to isolate the active constituents. Structures were established by HR-ESIMS, 1D and 2D NMR (1H, 13C, COSY, NOESY, HMBC, HSQC) spectroscopy. Two compounds were obtained and identified as isoflavanquinones: abruquinone A (1) and abruquinone B (2). Compounds 1 and 2 demonstrated significant (p < 0.05) antileishmanial activity against L. major (IC50 6.35 ± 0.005 μg/mL and 6.32 ± 0.008 μg/mL respectively) and L. tropica (IC50 6.29 ± 0.015 μg/mL and 6.31 ± 0.005 μg/mL, respectively). This appears to be the first report of antileishmanial activity of compounds 1 and 2 from the genus Abrus against cutaneous leishmaniasis and validates the use of A. precatorius in treating dermatology diseases.

The identification of biomolecules including protein and peptides is a crucial step for moving toward data collection and structure determination. The previous identification methods include analyzing crystal through X-ray diffraction, or using sophisticated instrument having a UV-radiation source and camera. However, not all laboratories are able to afford these costly techniques. Recently, some dyes are also available in the market for the identification of protein crystals. However, they are costly, and they might have a destructive effect on protein crystals. Keeping in mind the aforementioned points, we have identified a new dye which can be used for the identification of protein crystal. Lawsone (2-hydroxy-1,4-naphthoquinone) is a natural dye isolated from Eichhornia crassipe. The dye was tested on lysozyme, proteinase K, and thaumatin. The data of only lysozyme crystals was collected and processed. The result shows that there is no binding interaction of lawsone with lysozyme.

Picrotoxinin (1), a stable natural neurotoxin containing a highly oxygenated polycyclic rigid compound, was first isolated from berries of Anamirta cocculus (L.) Wight & Arn. (formerly known as Menispermum cocculus). The present work was aimed to study the modification of the complex polycyclic structure of picrotoxinin (1) by using microbial transformation. Initially various fungi, such as Macrophomina phaseolina, Cunninghamella blakesleeana, Aspergillus flavus, Aspergillus niger, Cephalosporium aphidicola, and Fusarium lini were screened for their ability to modify the structure of 1. Only one fungus Macrophomina phaseolina was able to catalyze the structural modification of picrotoxinin (1). The subsequent whole cell catalysis produced an intramolecular trans-esterified product 2. The structure of the transformed product was deduced by spectroscopic, and single-crystal X-ray diffraction analyses. A comparative study on convulsant activity of picrotoxinin (1) and its metabolite 2 was conducted in mice. Interestingly, metabolite 2 showed a delayed convulsant activity, as compared to the compound 1.

BACKGROUND Viscum album (the European mistletoe) is a semi-parasitic plant, which is of high medical interest. It is widely found in Europe, Asia, and North America. It contains at least three distinct lectins (i.e. ML-I, II, and III), varying in molecular mass and specificity. Among them, ML-I is in focus of medical research for various activities, including anti-cancer activities. To understand the molecular basis for such medical applications, a few studies have already addressed the structural and functional analysis of ML-I in complex with ligands. In continuation of these efforts, we are reporting the crystal structure of ML from Viscum album in complex with the nucleic acid oxidation product 4-N-furfurylcytosine (FC) refined to 2.85 A resolution. FC is known to be involved in different metabolic pathways related to oxidative stress and DNA modification. METHODS X-ray suitable hexagonal crystals of the ML-I/FC complex were grown within four days at 294 K using the hanging drop vapor diffusion method. Diffraction data were collected up to a resolution of 2.85 A. The ligand affinity was verified by in-silico docking. RESULTS The high-resolution structure was refined subsequently to analyze particularly the active site conformation and a binding epitope of 4-N-furfurylcytosine. A distinct 2Fo-Fc electron density at the active site was interpreted as a single FC molecule. The specific binding of FC is achieved also through hydrophobic interactions involving Tyr76A, Tyr115A, Glu165A, and Leu157A of the ML-I A-chain. The binding energy of FC to the active site of ML-I was calculated as well to be -6.03 kcal mol-1. CONCLUSION In comparison to other reported ML-I complexes, we observed distinct differences in the vicinity of the nucleic acid base binding site upon interaction with FC. Therefore, data obtained will provide new insights in understanding the specificity, inhibition, and cytotoxicity of the ML-I A-chain, and related RIPs.

Phytochemical studies on the root of Abrus precatorius Linn. (Fabaceae), leads towards the identification of four undescribed (abruquinones M, N, O, and P), and seven known abruquinones, (abruquinones A, E, B, F, I, D, and G). Spectroscopic analyses (1D, and 2D NMR, HRESI-MS) were used in elucidating structures of the all compounds. Evaluation of anticancer activities of the isolated isoflavanquinones revealed that abruquinones M, and N showed cytotoxicity against oral CAL-27 (IC50 values 6.48 and 5.26 μM, respectively), and colon (Caco-2) cell lines (IC50 values 15.79 and 10.33 μM, respectively). Abruquinone M also inhibited the growth of lung cancer cells (NCI–H460) with IC50 of 31.33 μM. The isolated isoflavanquiones also showed potent anti-inflammatory potential through phagocyte oxidative burst and pro-inflammatory cytokine TNF-α inhibition in vitro. These findings suggest isoflavanquinones from A. precatorius roots as candidates for further research in cancer treatment.

The applications of nanotechnology in different fields of medical science have revolutionized the healthcare sector for the diagnosis and treatment of several lethal diseases including cancer. Magnetic nanoparticles (MNPs) are one of the most used nanomaterials in disease diagnosis, targeted drug delivery, and biomedical imaging, such as magnetic resonance imaging (MRI). The unparalleled magnetic properties of the MNPs assigned certain characteristic features such as they can be used at the cellular and molecular level in a biological system and are also suitable materials to be used in drug delivery and MRI. The MNPs are in the front line, providing an attractive platform as alternative agents, as carriers in drug delivery and MRI. To better address the specific biomedical needs, MNPs with higher magnetic moments, specific size and surfaces, with enhanced functionalities, have great applications in the detection, diagnosis, targeted drug delivery, and treatment of different diseases such as cardiovascular disease, different types of malignant tumors, and neurological ailments. To date, various types of MNPs have been designed and synthesized according to their applications in detection of diseases, targeted drug delivery to various disease sites and different body parts, monitoring drug delivery, and also disease treatment. This chapter will provide an insight view of the design, synthesis, and applications of MNPs in disease diagnosis, targeted drug delivery, and MRI.

The microbial transformation of anabolic androgenic steroid mestanolone (1) with Macrophomina phaseolina and Cunninghamella blakesleeana has afforded seven metabolites. The structures of these metabolites were characterized as 17β-hydroxy-17α-methyl-5α-androsta-1-ene-3,11-dione (2), 14α,17β-dihydroxy-17α-methyl-5α-androstan-3,11-dione (3), 17β-hydroxy-17α-methyl-5α-androstan-1,14-diene-3,11-dione (4), 17β-hydroxy-17α-methyl-5α-androstan-3,11-dione (5), 11β,17β-dihydroxy-17α-methyl-5α-androstan-1-ene-3-one (6), 9α,11β,17β-trihydroxy-17α-methyl-5α-androstan-3-one (7), and 1β,11α,17β-trihydroxy-17α-methyl-5α-androstan-3-one (8). All the metabolites, except 5 and 6, were identified as new compounds. Substrate 1 (IC50 = 27.6 ± 1.1 μM), and its metabolites 2 (IC50 = 19.2 ± 2.9 μM) and 6 (IC50 = 12.8 ± 0.6 μM) exhibited moderate cytotoxicity against the HeLa cancer cell line (human cervical carcinoma). All metabolites were noncytotoxic to 3T3 (mouse fibroblast) and H460 (human lung carcinoma) cell lines. The metabolites were also evaluated for immunomodulatory activity, and all were found to be inactive.

The silver nanoparticles were synthesized, functionalized with afzelechin and characterized using UV-Visible spectroscopy. A difference of 20 nm was observed in surface plasmon resonance of bare and functionalized silver nanoparticles which indicates afzelechin conjugation with silver nanoparticles. The atomic force microscopy (AFM) technique was used for the determination of the size and morphology of synthesized silver nanoparticles. The afzelechin conjugated silver nanoparticles were spherical and their sizes ranged from 3 to 10 nm with an average size of 8 nm while the bare silver nanoparticles were also spherical and their sizes ranged from 3 to 10 nm with an average size of 6 nm. The average sizes were also calculated by fitting their UV-Visible absorption spectra. Fitting is based on the Mie and Mie Gans models, which deduced that afzelechin conjugated silver nanoparticles were 96.5% spherical and 3.5% spheroidal with an average size of 5 nm while bare silver nanoparticles were 100% spherical with an average size of 4 nm. Both the fitting model as well as the AFM results showed a difference of 3 nm between the sizes of afzelechin conjugated silver nanoparticles while 2 nm differences was observed for bare silver nanoparticles. The band gap energy of afzelechin conjugated silver nanoparticles and bare silver nanoparticles were calculated via Tauc’s equation and were found to be 5.1 eV and 5.4 eV, respectively. A difference of 0.3 eV was observed in band gap energies of afzelechin conjugated silver nanoparticles and bare silver nanoparticles.

Oilseeds of the plant family Brassicaceae are important for providing both lipid and protein contents to human nutrition. Cruciferins (12S globulins) are seed storage proteins, which are getting attention due to their allergenic and pathogenicity related nature. This study describes the purification and characterization of a trimeric (∼190 kDa) cruciferin protein from the seeds of Brassica nigra (L.). Cruciferin was first partially purified by ammonium sulfate precipitation (30% saturation constant) and further purified by size exclusion chromatography. The N-terminal amino-acid sequence analysis showed 82% sequence homology with cruciferin from Arabidopsis thaliana. The 50–55 kDa monomeric cruciferin produced multiple bands of two major molecular weight ranges (α-polypeptides of 28–32 kDa and β-polypeptides of 17–20 kDa) under reduced conditions of SDS-PAGE. The 2D gel electrophoretic analysis showed the further separation of the bands into their isoforms with major pI ranges between 5.7 and 8.0 (α-polypeptides) and 5.5–8.5 (β-polypeptides). The Dynamic Light Scattering (DLS) showed the monodisperse nature of the cruciferin with hydrodynamic radius of 5.8 ± 0.1 nm confirming the trimeric nature of the protein. The Circular Dichroism (CD) spectra showed both α-helices and β-sheets in the native conformation of the trimeric protein. The pure cruciferin protein (40 mg/ml) was successfully crystallized; however, the crystals diffracted only to low resolution data (8 A). Small-angle x-ray scattering (SAXS) was applied to gain insights into the three-dimensional structure in solution. SAXS showed that the radius of gyration is 4.24 ± 0.25 nm and confirmed the nearly globular shape. The SAXS based ab initio dummy model of B. nigra cruciferin was compared with 11S globulins (PDB ID: 3KGL ) of B. napus which further confirmed a highly similar molecular weight and globular shape indicating a conserved trimerization of B. nigra cruciferin. The comparison of the scattering patterns of both proteins showed a minimized χ2-value of 1.337 confirming a similar molecular structure. This is the first report describing the purification and characterization of a cruciferin protein from seeds of B. nigra.

Three new metabolites were obtained on incubation of androgenic steroid mesterolone ( 1 ) with Cunninghamella blakesleeana . These metabolites were identified as 1α-methyl-11 β ,14α,17β-trihydroxy-5α-androstan-3-one ( 2 ), 1α-methyl-7 β ,17 β -dihydroxy-5α-androstan-3-one ( 3 ), and 1α-methyl,17 β -hydroxy-5α-androstan-3,7-dione ( 4 ). During this study, hydroxylation at C-11, C-14, and C-15, and oxidation at C-7 of substrate 1 were observed. β -Hydroxylation at C-11 is a rather unique transformation by C. blakesleeana , as α-hydroxylation is reported to be catalyzed by most of the other microorganisms.

Two new prenylated flavonoids, thunbergiols A (1) and B (2), along with three known compounds, chrysin (3), quercetin (4) and berberine (5) were obtained from the methanolic extract of roots of Berberis thunbergii DC. MS, NMR and other spectroscopic techniques were employed for their structural characterisation.