Prevalence of Clostridium difficile in raw cow,sheep, and goat meat in Jazan,Saudi Arabia

Background:Clostridium difficile has been shown to be a nosocomial infection associated with diarrhoea and pseudomembranous colitis in hospitalized patients especially old patients. In my previous studies, it was shown the occurrence of C. difficile in animals feces and vegetables which may act as a source of infection to humans.The aim of the study was to determine the prevalence of C. difficile in retail raw cow, sheep, and goat, meat in Jazan, Saudi Arabia.Method: A total of 600 raw meat samples from cow, sheep, and goat were collected during June–December 2015, and tested for the presence of C. difficile. The method used to check for the presence of C. difficile was by choosing selective enrichment media in C. difficile broth, followed by alcohol shock-treatment and plating onto C. difficile selective medium. C. difficile isolates were typed using PCR ribotyping and also analyzed for antibiotic susceptibility.Results: It was shown that, 9 of 600 meat samples (1.5%) were contaminated with C. difficile. The prevalence of C. difficile was as follow: 7 out of 600 (1.17%) were found in cow, 2 out of 600 (0.3%) were found in sheep, while was no C. difficile was isolated from goat. Eleven out of 18 C. difficile isolates were positive for tcdA, tcdB and cdtB toxin genes and were classified as ribotype 078. Three strains were positive tcdA, and tcdB, and two strains possessed only tcdB. C. difficile strains showed high resistance to ampicillin, gentamycin, erythromycin and nalidixic acid.Conclusions: The present work shows the potential risk of raw meet in transmitting C. difficile to humans.     

Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis,biological activity,and molecular modelling studies

An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1–3 Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.     

A newly synthesized 6-methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8-one for potential inhibitor of adenosine A1 receptor: a combined experimental and computational studies

Abstract

6-Methyl-7H,8H,9H-[1,2,4]triazolo[4,3-b][1,2,4]triazepin-8-onehas been synthesized, characterized by spectroscopic techniques (FT-IR, ¹H and ¹³C NMR) and finally the structure was confirmed by single crystal X-ray diffraction studies. In the title molecule, C₆H₇N₅O, the 7-membered ring adopts a bowl-like conformation. In the crystal, the molecules form stacks along the c-axis direction through offset π-stacking interactions between the 5-membered rings and C–H···N hydrogen bonds. The stacks are associated via a combination of N–H···N, C–H···O and C–H···N hydrogen bonds. Further, the Hirshfeld surface analysis reveals the nature of molecular interactions and the fingerprint plot provides information about the percentage contribution from each individual molecular contact to the surface. In addition, due to its biological interest the target molecule adenosine A1 receptor was found based on Structural Activity Relationship (SAR) analysis and, further, subjected into molecular docking and molecular dynamics analysis to understand the binding interaction and stability of the molecule in adenosine A1 receptor system. Furthermore, the Density Functional Theory (DFT) calculations were carried for free compound and the compound in active site (single point DFT), to know the internal stability.

Communicated by Ramaswamy H. Sarma