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Katharigatta N Venugopala, 1, 2 Christophe Tratrat, 1 Melendhran Pillay, 3 Sandeep Chandrashekharappa, 4 Omar Husham Ahmed Al-Attraqchi, 5 Bandar E Aldhubiab, 1 Mahesh Attimarad, 1 Osama I Alwassil, 6 Anroop B Nair, 1 Nagaraja Sreeharsha, 1 Rashmi Venugopala, 7 Mohamed A Morsy, 1, 8 Michelyne Haroun, 1 Hezekiel M Kumalo, 9 Bharti Odhav, 2 Koleka Mlisana 3 1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Kingdom of Saudi Arabia; 2Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa; 3Department of Microbiology, National Health Laboratory Services, KZN Academic Complex, Inkosi Albert Luthuli Central Hospital, Durban 4001, South Africa; 4Institute for Stem Cell Biology and Regenerative Medicine, NCBS, TIFR, Bangalore 560 065, India; 5Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan; 6Department of Pharmaceutical Sciences, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 7Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban 4001, South Africa; 8Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia 61511, Egypt; 9Department of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Medical School, Durban 4001, South AfricaCorrespondence: Katharigatta N VenugopalaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, P.o. Box-400, Al-Ahsa 31982, Kingdom of Saudi ArabiaTel +96613 589 8842Email kvenugopala@kfu.edu.saSandeep ChandrashekharappaInstitute for Stem Cell Biology and Regenerative Medicine, National Center for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bellary Road, Bangalore 560 065, IndiaTel +9194486 39413Email sandeepc@instem.res.inBackground and Purpose: Tuberculosis has been reported to be the worldwide leading cause of death resulting from a sole infectious agent. The emergence of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis has made the battle against the infection more difficult since most currently available therapeutic options are ineffective against these resistant strains. Therefore, novel molecules need to be developed to effectively treat tuberculosis disease. Preliminary docking studies revealed that tetrahydropyrimidinone derivatives have favorable interactions with the thymidylate kinase receptor. In the present investigation, we report the synthesis and the mycobacterial activity of several pyrimidinones and pyrimidinethiones as potential thymidylate kinase inhibitors.Methods: The title compounds ( 1a–d) and ( 2a–b) were synthesized by a one-pot three-component Biginelli reaction. They were subsequently characterized and used for whole-cell anti-TB screening against H37Rv and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) by the resazurin microplate assay (REMA) plate method. Molecular modeling was conducted using the Accelry’s Discovery Studio 4.0 client program to explain the observed bioactivity of the compounds. The pharmacokinetic properties of the synthesized compounds were predicted and analyzed.Results: Of the compounds tested for anti-TB activity, pyrimidinone 1a and pyrimidinethione 2a displayed moderate activity against susceptible MTB H37Rv strains at 16 and 32 μg/mL, respectively. Only compound 2a was observed to exert modest activity at 128 μg/mL against MTB strains with cross-resistance to rifampicin and isoniazid. The presence of the trifluoromethyl group was essential to retain the inhibitory activity of compounds 1a and 2a. Molecular modeling studies of these compounds against thymidylate kinase targets demonstrated a positive correlation between the bioactivity and structure of the compounds. The in-silico ADME (absorption, distribution, metabolism, and excretion) prediction indicated favorable pharmacokinetic and drug-like properties for most compounds.Conclusion: Pyrimidinone 1a and pyrimidinethione 2a were identified as the leading compounds and can serve as a starting point to develop novel anti-TB therapeutic agents.Keywords: thymidylate kinase inhibitors, tetrahydropyrimidinones, tetrahydropyrimidinethiones, multidrug resistance, Mycobacterium tuberculosis, molecular modeling

Katharigatta N Venugopala,1,2 Reshme Govender,2 Mohammed A Khedr,1,3 Rashmi Venugopala,4 Bandar E Aldhubiab,1 Sree Harsha,1 Bharti Odhav2 1Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Kingdom of Saudi Arabia; 2Department of Biotechnology and Food Technology, Durban University of Technology, Durban, South Africa; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, Egypt; 4Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban, South Africa Abstract: Dihydropyrimidine scaffold has a wide range of potential pharmacological activities such as antiviral, antitubercular, antimalarial, anti-inflammatory, and anticancer properties. 5-Lipoxygenase enzyme is an enzyme responsible for the metabolism of arachidonic acid to leukotrienes. The elevated levels of this enzyme and its metabolites in cancer cells have a direct relation on the development of cancer when compared to normal cells. The development of novel lipoxygenase inhibitors can have a major role in cancer therapy. A series of substituted 1,4-dihydropyrimidine analogues were synthesized and characterized by 1H-NMR, 13C-NMR, and HRMS. Molecular docking against lipoxygenase enzyme (protein data bank code =3V99) was done using Molecular Operating Environment 2013.08 and Leadit 2.1.2 softwares and showed high affinities. The synthesized compounds were tested for their lipoxygenase inhibitory activity and showed inhibition ranging from 59.37%±0.66% to 81.19%±0.94%. The activity was explained by a molecular docking study. The title compounds were also tested for cytotoxic activity against two human cancer cell lines Michigan Cancer Foundation-7 and human melanoma cells and a normal peripheral blood mononuclear cell line. Keywords: 1,4-dihydropyrimidines, synthesis and characterization, molecular docking study

Coumarin (2H-1-benzopyran-2-one) is a plant-derived natural product known for its pharmacological properties such as anti-inflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihypertensive, antitubercular, anticonvulsant, antiadipogenic, antihyperglycemic, antioxidant, and neuroprotective properties. Dietary exposure to benzopyrones is significant as these compounds are found in vegetables, fruits, seeds, nuts, coffee, tea, and wine. In view of the established low toxicity, relative cheapness, presence in the diet, and occurrence in various herbal remedies of coumarins, it appears prudent to evaluate their properties and applications further. [ABSTRACT FROM AUTHOR]

Abstract: In this report, we present preliminary nutritional data for traditional leafy vegetables collected in Kwa Zulu-Natal, South Africa, including their content of mineral elements (Ca, P, Na, Zn, Mg, Mn and Fe) and antioxidant levels. Twenty vegetables were studied: Amaranthus dubius, Amaranthus hybridus, Amaranthus spinosus, Asystasia gangetica, Bidens pilosa, Centella asiatica, Ceratotheca triloba, Chenopodium album, Cleome monophylla, Cucumis metuliferus, Emex australis, Galinsoga parviflora, Justicia flava, Momordica balsamina, Oxygonum sinuatum, Physalis viscosa, Portulaca oleracea, Senna occidentalis, Solanum nodiflorum and Wahlenbergia undulata. The results of this study provide evidence that these local traditional vegetables, which do not require formal cultivation, could be important contributors to improving the nutritional content of rural and urban people. From this study, it was determined that twelve leafy vegetables, namely A. dubius, A. gangetica, A. hybridus, A. spinosus, C. metuliferus, C. monophylla, C. triloba, G. parviflora, J. flava, M. balsamina, P. viscosa and W. undulata provide mineral concentrations exceeding 1% of plant dry weight and are much higher than typical mineral concentrations in conventional edible leafy vegetables; they are thus recommended for future commercial cultivation. High levels of antioxidant activity (96%) were noticed in J. flava and P. oleraceae. [Copyright &y& Elsevier]

In this study, Fusarium species isolated from 29 patients with mycotic keratitis were identified and tested for their ability to produce mycotoxins. Members of the F. solani species complex ( Fs complex) were the predominant species isolated, followed by F. verticillioides, F. dimerum, members of the F. oxysporum species complex Fo complex), F. incarnatum, F. chlamydosporum and F. lateritium. Of these, 76% of the Fusarium isolates produced fusaric acid, moniliformin or fumonisin B1. Many of the fusaria isolated are common aetiological agents of mycotic keratitis infections. However, F. incarnatum, F. chlamydosporum and F. lateritium have previously not been found in this infection. These findings indicate that a greater variety of fusarial species are becoming associated with mycotic keratitis infections. This paper further demonstrates the mycotoxin-producing ability of these clinical isolates and assesses cellular cytotoxicity. [ABSTRACT FROM AUTHOR]

Describes how industrial effluents and leachates from hazardous landfill sites were tested for toxicity using the anaerobic toxicity assay. Use of brewery spent grain effluent and a chemical industry effluent; How the chemical industry effluent was found to be most toxic; Findings that the leachate from Holfontein hazardous landfill site was least biodegradable.

Traditionally brewed alcoholic beverages are regularly consumed by most ethnic black South Africans. Maize and barley, both of which are used for producing locally brewed alcoholic beer, are frequently contaminated by mycotoxin-producing moulds. The study was undertaken to investigate whether these toxins are present in raw grains and the traditional beers imbibed by the local black African population. It was established that the raw ingredients (sorghum, sorghum malt grains, maize grits), commercially produced traditional beers (Utshwala and Utshwala special) and home-brewed beers (Umqombotha, Isiqatha, Imfulamfula) were contaminated by bacteria and fungi (both yeasts and moulds). The contaminating moulds were isolated and identified. The contaminated samples were analysed for aflatoxins B[sub 1], B[sub 2], G[sub 1] and G[sub 2], zearalenone, citrinin, deoxynivalenol, and ochratoxin A using a multi-mycotoxin thin-layer chromatography screening method and the toxins were quantified by high-performance liquid chromatography. Grain samples were infected by Aspergillus flavus, A. alliaceus, A. clavatus, Penicillium spp., Rhizopus spp. and Mucor spp. Sorghum malt grain samples contained the toxin zearalenone. No mycotoxin-producing fungi were present in the fermented beers but two of six commercial beer samples contained aflatoxins (200 and 400 μgl[sup -1]) and 45% (13 of 29) of the home-brewed beers had zearalenone (range 2.6-426 μg l[sup -1]) and/or ochratoxin A (3-2340 μg l[sup -1]). [ABSTRACT FROM AUTHOR]

An externally unskinned polysulfone ultrafiltration capillary membrane was used as an immobilisation matrix for the white rot basidiomycete Phanerochaete chrysosporium ME446. In this study, different membrane bioreactor configurations, scanning electron microscopy, atomic force microscopy and enzyme assays were used to characterise the spatial distribution of spores after immobilisation by reverse filtration and document the subsequent growth phases. A single capillary membrane bioreactor was also used to develop and evaluate a spore immobilisation technique by modifying conventional bioreactor configurations for reverse filtration onto the external surface of the membrane. Results indicate that spore immobilisation was dependent on a differential pressure across the tube wall and the fluid flow pattern in the tube, thus influencing the spatial distribution of spores along the surface and within the microvoids in the membrane wall. The resultant radial and lateral biofilm development using this reverse filtration approach promoted uniform biomass development, which favoured manganese peroxidase production. [Copyright &y& Elsevier]