Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design,synthesis, molecular docking studies and ADMET prediction

Two series of chalcone/aryl carboximidamide hybrids 4a–f and 6a–f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.     

Quest for Novel Preventive and Therapeutic Options Against Multidrug-Resistant Pseudomonas aeruginosa

International Journal of Peptide Research and Therapeutics - Pseudomonas aeruginosa (P. aeruginosa) is a critical healthcare challenge due to its ability to cause persistent infections and the...     

Effect of adding plyometric training to physical education sessions on specific biomechanical parameters in primary school girls

Objectives:The study aimed to determine the effect of adding a school-based plyometric training program (PMT) to physical education (PE) sessions on the strength, balance, and flexibility in primary school girls.Methods:Students from grades 3-6 were randomized equally to a plyometric or control group. In the control group, students took their regular PE classes twice a week. In the plyometric group, students performed PMT twice a week during the initial 20 minutes of every PE session. The Lido Linea closed kinetic chain isokinetic dynamometer, Star excursion balance test (SEBT), and sit-and-reach test were used to assess muscle strength, balance, and flexibility, respectively, before and after nine weeks of training.Results:The improvement in extension peak force (p=0.04) and extension total work (p<0.001) was more prevalent in the PMT group than in the control group. SEBT scores had improved significantly (p<0.05) for all directions in the PMT group, except in the anterior direction, which was highly significant (p<0.001). Hamstring and lower back flexibility had improved more in the PMT group than in the control group (p<0.001).Conclusion:Adding PMT to regular PE classes has a positive and notable effect on muscle strength, balance, and flexibility in primary school students.     

Characterization of the native honey bee (Apis mellifera jemenitica) in the south western region of Saudi Arabia using morphometric and genetic (mtDNA COI) characteristics

Apis mellifera jemenitica incorporates a few perceived subspecies that vary in their natural properties and farming qualities. Mitochondrial COI gene sequence (mtCOI) has not been used before for bee identification in the southwestern region of Saudi Arabia. The aim of this work was to study the morphometry and analyzing the mtCOI of all collected bees. The nucleotide sequence of the mtCOI gene was analyzed. Similarity searches and distances between each obtained DNA and sequences available in GenBank were made. Morphometric analysis revealed close similarities among the studied bees, but these similarities are different from those previously indicated in earlier studies of the same region. Molecular studies revealed that the collected bees are similar to each other and some other sequences found in GenBank, but these bees are a new hybrid or subspecies that are different from those previously reported in the same region, indicating the emergence of a new hybrid.     

Diversity of trypanosomes in humans and cattle in the HAT foci Mandoul and Maro,Southern Chad—A matter of concern for zoonotic potential?

BackgroundAfrican trypanosomes are parasites mainly transmitted by tsetse flies. They cause trypanosomiasis in humans (HAT) and animals (AAT). In Chad, HAT/AAT are endemic. This study investigates the diversity and distribution of trypanosomes in Mandoul, an isolated area where a tsetse control campaign is ongoing, and Maro, an area bordering the Central African Republic (CAR) where the control had not started.Methods717 human and 540 cattle blood samples were collected, and 177 tsetse flies were caught. Trypanosomal DNA was detected using PCR targeting internal transcribed spacer 1 (ITS1) and glycosomal glyceraldehyde-3 phosphate dehydrogenase (gGAPDH), followed by amplicon sequencing.ResultsTrypanosomal DNA was identified in 14 human samples, 227 cattle samples, and in tsetse. Besides T. b. gambiense, T. congolense was detected in human in Maro. In Mandoul, DNA from an unknown Trypanosoma sp.-129-H was detected in a human with a history of a cured HAT infection and persisting symptoms. In cattle and tsetse samples from Maro, T. godfreyi and T. grayi were detected besides the known animal pathogens, in addition to T. theileri (in cattle) and T. simiae (in tsetse). Furthermore, in Maro, evidence for additional unknown trypanosomes was obtained in tsetse. In contrast, in the Mandoul area, only T. theileri, T. simiae, and T. vivax DNA was identified in cattle. Genetic diversity was most prominent in T. vivax and T. theileri.ConclusionTsetse control activities in Mandoul reduced the tsetse population and thus the pathogenic parasites. Nevertheless, T. theileri, T. vivax, and T. simiae are frequent in cattle suggesting transmission by other insect vectors. In contrast, in Maro, transhumance to/from Central African Republic and no tsetse control may have led to the high diversity and frequency of trypanosomes observed including HAT/AAT pathogenic species. Active HAT infections stress the need to enforce monitoring and control campaigns. Additionally, the diverse trypanosome species in humans and cattle indicate the necessity to investigate the infectivity of the unknown trypanosomes regarding their zoonotic potential. Finally, this study should be widened to other trypanosome hosts to capture the whole diversity of circulating trypanosomes.     

In silico molecular docking analysis for repurposing approved antiviral drugs against SARS-CoV-2 main protease

Developing a safe and effective antiviral treatment takes a decade, however, when it comes to the coronavirus disease (COVID-19), time is a sensitive matter to slow the spread of the pandemic. Screening approved antiviral drugs against COVID-19 would speed the process of finding therapeutic treatment. The current study examines commercially approved drugs to repurpose them against COVID-19 virus main protease using structure-based in-silico screening. The main protease of the coronavirus is essential in the viral replication and is involved in polyprotein cleavage and immune regulation, making it an effective target when developing the treatment. A Number of approved antiviral drugs were tested against COVID-19 virus using molecular docking analysis by calculating the free natural affinity of the binding ligand to the active site pocket and the catalytic residues without forcing the docking of the ligand to active site. COVID-19 virus protease solved structure (PDB ID: 6LU7) is targeted by repurposed drugs. The molecular docking analysis results have shown that the binding of Remdesivir and Mycophenolic acid acyl glucuronide with the protein drug target has optimal binding features supporting that Remdesivir and Mycophenolic acid acyl glucuronide can be used as potential anti-viral treatment against COVID-19 disease.     

Introduction of histidine units using benzotriazolide activation

N^α‐Boc‐N^im‐(4‐toluenesulfonyl‐l ‐histidylbenzotriazole) enables convenient acylation of N‐, O‐, S‐, and C‐nucleophiles with no detectable racemization. We report efficient syntheses of novel histidine‐containing di‐, tri‐, and tetra‐peptides and models for the preparation of potentially biologically active histidine N‐, O‐, S‐, and C‐conjugates. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Purification of carbonic anhydrase from dog erythrocytes and investigation of in vitro inhibition by various compounds

The enzyme carbonic anhydrase (E.C. 4.2.1.1) has a stimulatory effect on glaucoma, an eye disease that has a risk to dogs, which are models for the human eye disease, that is similar to that in humans.

In this study, some sulfonamide derivatives, 2-(3-cyclohexene-1-carbamido)-1,3,4-thiadiazole-5-sulfonamide (CCTS), 4-(3-cyclohexene-1-carbamido) methyl-benzenesulfonamide (CCBS), 2-(9-octadecenoylamido)-1,3,4-thiadiazole-5-sulfonamide (ODTS), 2-(4,7,10-trioxa-tetradecanoylamido)-1,3,4-thiadiazole-5-sulfonamide (TDTS), and 2-(8-methoxycoumarine-3-carbamido)-1,3,4-thiadiazole-5-sulfonamide (MCTS), as well as some anionic compounds (perchlorate and chloride) and existing medicines (dorzolamide-HCl, gentamicine sulphate, tropicamide, and procaine-HCl) were assayed for their inhibition of dog carbonic anhydrase (dCA), which was purified from erythrocytes on an affinity gel of L-tyrosine-sulfonamide-Sepharose 4B. ODTS showed the highest potency amongst the synthetic compounds with IC₅₀ value 1.18 × 10^{? 5} M. Amongst the medicines tested, only dorzolamide showed inhibition with IC₅₀ value 5.05 × 10^{? 4} M. Procaine and tropicamide actually showed an activatory effect, whereas gentamicine sulfate had no significant effect. The inhibitory effects of anionic compounds such as perchlorate and chloride were also investigated; whereas perchlorate showed inhibition, chloride did not.