Entanglement Swapping and Swapped Entanglement.

Entanglement swapping is gaining widespread attention due to its application in entanglement distribution among different parts of quantum appliances. We investigate the entanglement swapping for pure and noisy systems, and argue different entanglement quantifiers for quantum states. We explore the relationship between the entanglement of initial states and the average entanglement of final states in terms of concurrence and negativity. We find that if initial quantum states are maximally entangled and we make measurements in the Bell basis, then average concurrence and average negativity of final states give similar results. In this case, we simply obtain the average concurrence (average negativity) of the final states by taking the product of concurrences (negativities) of the initial states. However, the measurement in non-maximally entangled basis during entanglement swapping degrades the average swapped entanglement. Further, the product of the entanglement of the initial mixed states provides an upper bound to the average swapped entanglement of final states obtained after entanglement swapping. The negativity work well for weak entangled noisy states but concurrence gives better results for relatively strong entanglement regimes. We also discuss how successfully the output state can be used as a channel for the teleportation of an unknown qubit.

Innovative Strategies to Overcome Antimicrobial Resistance and Tolerance.

Antimicrobial resistance and tolerance are natural phenomena that arose due to evolutionary adaptation of microorganisms against various xenobiotic agents. These adaptation mechanisms make the current treatment options challenging as it is increasingly difficult to treat a broad range of infections, associated biofilm formation, intracellular and host adapted microbes, as well as persister cells and microbes in protected niches. Therefore, novel strategies are needed to identify the most promising drug targets to overcome the existing hurdles in the treatment of infectious diseases. Furthermore, discovery of novel drug candidates is also much needed, as few novel antimicrobial drugs have been introduced in the last two decades. In this review, we focus on the strategies that may help in the development of innovative small molecules which can interfere with microbial resistance mechanisms. We also highlight the recent advances in optimization of growth media which mimic host conditions and genome scale molecular analyses of microbial response against antimicrobial agents. Furthermore, we discuss the identification of antibiofilm molecules and their mechanisms of action in the light of the distinct physiology and metabolism of biofilm cells. This review thus provides the most recent advances in host mimicking growth media for effective drug discovery and development of antimicrobial and antibiofilm agents.

In silico identification of potential inhibitors of key SARS-CoV-2 3CL hydrolase (Mpro) via molecular docking, MMGBSA predictive binding energy calculations, and molecular dynamics simulation.

The incidence of 2019 novel corona virus (SARS-CoV-2) has created a medical emergency throughout the world. Various efforts have been made to develop the vaccine or effective treatments against the disease. The discovery of crystal structure of SARS-CoV-2 main protease has made the in silico identification of its inhibitors possible. Based on its critical role in viral replication, the viral protease can prove to be a promising "target" for antiviral drug therapy. We have systematically screened an in-house library of 15,754 natural and synthetic compounds, established at International Center for Chemical and Biological Sciences, University of Karachi. The in silico search for potential viral protease inhibitors resulted in nine top ranked ligands (compounds 1-9) against SARS-CoV-2 main protease (PDB ID: 6LU7) based on docking scores, and predictive binding energies. The in silico studies were updated via carrying out the docking, and predictive binding energy estimation, with a recently reported crystal structure of main protease (PDB ID: 6Y2F) at a better resolution i.e., 1.95 Å. Compound 2 (molecular bank code AAA396) was found to have highest negative binding energy of -71.63 kcal/mol for 6LU7. While compound 3 (molecular bank code AAD146) exhibited highest negative binding energy of -81.92 kcal/mol for 6Y2F. The stability of the compounds- in complex with viral protease was analyzed by Molecular Dynamics simulation studies, and was found to be stable over the course of 20 ns simulation time. Compound 2, and 3 were predicted to be the significant inhibitors of SARS-CoV-2 3CL hydrolase (Mpro) among the nine short listed compounds.

Metabolite Profiling and Quantitation of Cucurbitacins in Cucurbitaceae Plants by Liquid Chromatography coupled to Tandem Mass Spectrometry.

Cucurbitaceae is an important plant family because many of its species are consumed as food, and used in herbal medicines, cosmetics, etc. It comprises annual vines and is rich in various bioactive principles which include the cucurbitacins. These steroidal natural products, derived from the triterpene cucurbitane, are mainly the bitter principles of the family Cucurbitaceae. Their biological activities include anti-inflammatory, hepatoprotective, and anti-cancer activities. A total of 10 species belonging to 6 genera of the Cucurbitaceae family along with Cissampelos pareira (Menispermaceae) were included in this study. A comprehensive profiling of certain natural products was developed using HPLC-QTOF-MS/MS analysis and a distribution profile of several major natural products in this family was obtained. A total of 51 natural products were detected in both positive and negative ionization modes, based on accurate masses and fragmentation patterns. Along with this, quantitation of four bioactive cucurbitacins, found in various important plants of the Cucurbitaceae family, was carried out using multiple reaction monitoring (MRM) approach on an ion trap mass spectrometer. Cucurbitacin Q was found to be the most abundant in C. pareira, while Citrullus colocynthis contained all four cucurbitacins in abundant quantities. The developed quantitation method is simple, rapid, and reproducible.

Anthranilic Acid Derivatives: Novel Inhibitors of Protein Glycation and the Associated Oxidative Stress in the Hepatocytes.

BACKGROUND: Anthranilic acid derivatives are important pharmacophores in drug discovery. Several of them are currently being used, such as mefenamic acid and meclofenamates, possess analgesic, anti-inflammatory and antipyretic activities. Some anthranilic acid-based scaffolds have also been reported for the management of metabolic disorders. OBJECTIVES: The aim of the current study was to investigate the antiglycation potential of 2-anilino benzoic acid derivatives against (N-phenylanthranilic acid) fructose- human serum albumin (HSA) glycation. The study also analyzed the effects of newly identified antiglycation inhibitors on AGEs-mediated intracellular reactive oxygen species production, and associated impaired proliferation of the hepatocytes. METHODS: The present study focuses on the antiglycation activity of 2- anilinobenzoic acid derivatives 1-18 in in-vitro human serum albumin (HSA)- fructose model. These derivatives were also identified as non-toxic to 3T3 mouse fibroblast cell-line using metabolic assay. The effect of the most promising derivative 1, 2- (2, 4- dinitroanilino)benzoic acid, was studied in a dose dependent manner, co-incubated with fructose-derived AGEs (0- 200 µg/mL), on rat hepatocytes proliferation and associated intracellular generation of ROS via MTT assay and DCFH-DA technique, respectively. RESULTS: We found that derivative 1 ameliorates the elevated intracellular oxidative stress and associated diminished proliferation of the hepatocytes in response to AGEs. CONCLUSION: In conclusion, we identify novel 2- anilino benzoic acid derivatives as antiglycation agents through in-vitro and cellular-based models.

Oxidation of lynestrenol by the fungus Cunninghamella elegans.

Transformation of lynestrenol (19-nor-17alpha-pregn-4-en-20-yn-17beta-ol) (1) was carried out by incubation with Cunninghamella elegans to obtain 19-nor-17alpha-pregn-4-en-20-yn-3-one-10beta,17beta-diol (2), 19-nor-17alpha-pregn-4-en-20-yn-3-one-6beta,17beta-diol (3), and 19-nor-17alpha-pregn-4-en-20-yn-3beta,6beta,17beta-triol (4). Metabolite 4 was identified as a new compound. These metabolites were structurally characterised on the basis of spectroscopic techniques.

Microbial transformation of oleanolic acid by Fusarium lini and alpha-glucosidase inhibitory activity of its transformed products.

The biotransformation of a pentacyclic triterpene, oleanolic acid (1), with Fusarium lini afforded two oxidative metabolites, 2alpha,3beta-dihydroxyolean-12-en-28-oic acid (2), and 2alpha,3beta,11beta-trihydroxyolean-12-en-28-oic acid (3). Metabolite 3 was found to be a new compound. The structures were characterized on the basis of spectroscopic studies. These metabolites exhibited a potent inhibition of alpha-glucosidase enzyme.

Biotransformation of (-)-ambrox by cell suspension cultures of Actinidia deliciosa.

Biotransformation of (-)-ambrox (1) with cell suspension cultures of Actinidia deliciosa (Kiwifruit) yielded the regio- and stereospecific oxygenated products 3-oxoambrox (2), 3beta-hydroxyambrox (3), 1alpha-hydroxyambrox (4), 3beta,6beta-dihydroxyambrox (5), 1alpha,6beta-dihydroxyambrox (6), and 1alpha,3beta-dihydroxyambrox (7). Metabolites 6 and 7 were found to be new compounds. These metabolites were structurally characterized on the basis of spectroscopic studies. The structure of compound 6 was unambiguously deduced by single-crystal X-ray diffraction techniques. Metabolites 2-7 were evaluated for in vitro inhibitory activity against the thymidine phosphorylase enzyme.

Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties.

The withanolides 1-3 and 4-5 isolated from Ajuga bracteosa and Withania somnifera, respectively, inhibited acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8) enzymes in a concentration-dependent fashion with IC50 values ranging between 20.5 and 49,2 microm and 29.0 and 85.2 microm for AChE and BChE, respectively. Lineweaver-Burk as well as Dixon plots and their secondary replots indicated that compounds 1, 3, and 5 are the linear mixed-type inhibitors of AChE, while 2 and 4 are non-competitive inhibitors of AChE with K(i) values ranging between 20.0 and 45.0 microm. All compounds were found to be non-competitive inhibitors of BChE with K(i) values ranging between 27.7 and 90.6 microm. Molecular docking study revealed that all the ligands are completely buried inside the aromatic gorge of AChE, while compounds 1, 3, and 5 extend up to the catalytic triad. A comparison of the docking results showed that all ligands generally adopt the same binding mode and lie parallel to the surface of the gorge. The superposition of the docked structures demonstrated that the non-flexible skeleton of the ligands always penetrates the aromatic gorge through the six-membered ring A, allowing their simultaneous interaction with more than one subsite of the active center. The affinity of ligands with AChE was found to be the cumulative effects of number of hydrophobic contacts and hydrogen bonding. Furthermore, all compounds also displayed dose-dependent (0.005-1.0 mg/mL) spasmolytic and Ca2+ antagonistic potentials in isolated rabbit jejunum preparations, compound 4 being the most active with an ED50 value of 0.09 +/- 0.001 mg/mL and 0.22 +/- 0.01 microg/mL on spontaneous and K+ -induced contractions, respectively. The cholinesterase inhibitory potential along with calcium antagonistic ability and safe profile in human neutrophil viability assay could make compounds 1-5 possible drug candidates for further study to treat Alzheimer's disease and associated problems.

Microbial transformation of mestranol by Cunninghamella elegans.

The microbial transformation of an oral contraceptive, mestranol (1) by Cunninghamella elegans yielded two hydroxylated metabolites, 6beta-hydroxymestranol (2) and 6beta,12beta-dihydroxymestranol (3). Metabolite 3 was found to be a new compound. These metabolites were structurally characterized on the basis of spectroscopic techniques.

Leucosceptrine--a novel sesterterpene with prolylendopeptidase inhibitory activity from Leucosceptrum canum.

A novel sesterterpene, leucosceptrine, was isolated from the medicinal plant Leucosceptrum canum from Nepal. The structure was determined by single-crystal X-ray diffraction and spectroscopic techniques. The biosynthesis of leucosceptrine (1) is proposed here. Leucosceptrine (1) exhibited prolylendopeptidase inhibitory activity.

Two isoflavones and bioactivity spectrum of the crude extracts of Iris germanica rhizomes.

In vitro biological activities including bactericidal, fungicidal and insecticidal activities as well as phytotoxicity and brine shrimp toxicity of the petroleum ether, chloroform and ethyl acetate extracts of Iris germanica L. were determined. The bactericidal activity of the extracts was assayed by the agar well diffusion test. In the fungicidal test, the agar tube dilution method was used. The insecticidal activity was determined by the exposure method. The toxicity of the extracts was evaluated by the phytotoxicity test as well as the brine shrimp toxicity test. The chloroform and ethyl acetate extracts of I. germanica rhizomes exhibited bactericidal activity, while the petroleum ether extract did not exhibit any bactericidal, fungicidal and insecticidal activities. It was also inactive in the brine shrimp toxicity test, whereas it showed significant phytotoxicity against the plant Lemna aequinoctialis Welv. Two known isoflavones were isolated from the chloroform extract of the plant.

Withanolides from Withania coagulans.

Two withanolides, 20beta-hydroxy-1-oxo-(22R)-witha-2,5,24-trienolide (1) and withacoagulin (2), along with a known withanolide, 17beta-hydroxy-14alpha, 20alpha-epoxy-1-oxo-(22R)-witha-3,5,24-trienolide (3) were isolated from Withania coagulans. Their structures were elucidated with the help of different spectroscopic techniques.