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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

Background: The traditional African herbal medicinal system has many reports of anti-diabetic food plants with no known side effects. Such plants and their products have been widely prescribed for diabetic treatment with little known mechanistic basis of their functioning. Therefore, these natural products need to be evaluated scientifically in order to confirm antidiabetic property claims.Materials and Methods: In this study, leaves of Brachylaena discolor were evaluated for potential to inhibit α-amylase and α-glucosidase. The leaves were also screened for toxicity and free radical scavenging capacity.Results: Results from the study show that the methanolic extract gave a higher α-glucosidase inhibition potential and was able to effectively scavenge free radicals better than the aqueous extract. The toxicity, cytotoxicity and mutagenicity screen also showed that both plant extracts are safe for use.Conclusion: These results therefore indicate that B. discolor has the potential for use as a potential dietary adjunct or therapy for the treatment of diabetes.Key words: Brachylaena discolor, α-amylase, α-glucosidase, DPPH, toxicity

Extracts of selected flowering plants, which are considered eco-friendly, are used for the treatment of numerous ailments and vector control worldwide. This has resulted in approximately 25 per cent of currently used drugs being derived from herbal sources. The aqueous and methanolic extracts of twelve plant species, Psidium guajava (pink fruit), Psidium guajava (white fruit), Psidium cattleianum var. cattleianum, Psidium guineense and Psidium X durbanensis, Achyranthes aspera, Alternanthera sessilis, Guilleminea densa, Capparis tomentosa, Leonotis leonurus, Dichrostachys cinerea and Carpobrotus dimidiatus, were tested for insecticidal activity, including larvicidal, adulticidal and repellent activities against the adult female mosquito, Anopheles arabiensis. The extracts of P. guajava (white fruit), C. tomentosa, L. leonurus,D. cinerea, and C. dimidiatus exerted a pronounced inhibitory effect on adult insects, while those of P. guajava (pink fruit), P. X durbanensis, P. cattleianum var. cattleianum, P. guineense, A. aspera, A. sessilis, and G. densa were ineffective and failed to satisfy the criteria set by the World Health Organization. In the tests for repellency against An. arabiensis, all the tested aqueous and methanolic plant extracts except those of A. sessilis repelled 80-100% of mosquitoes. The most effective mosquito repellents were the methanol and aqueous extracts of P. guajava (pink fruit), P. X durbanensis, P. cattleianum var. cattleianum, P. guineense, G. densa,L. leonurus and D. cinerea, which are potential sources of cost effective mosquito repellents to be utilized in malarial endemic areas. Fil: Chalannavar, R.K.. Durban University of Technology; Sudáfrica Fil: Hurinanthan, V.. Durban University of Technology; Sudáfrica Fil: Singh, Ajnesh. Durban University of Technology; Sudáfrica Fil: Venugopala, K.N.. Durban University of Technology; Sudáfrica Fil: Gleiser, Raquel M.. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Baijnath, H.. Durban University of Technology; Sudáfrica Fil: Odhav, B.. Durban University of Technology; Sudáfrica

Hypoxis rigidula Baker var. rigidula and Hypoxis hemerocallidea Fisch., C.A.Mey. & Avé-Lall (Hypoxidaceae) are frequently used African medicinal plant that has been used by traditional healers for daily healthcare needs. Phytosterols isolated from Hypoxis spp, have been found to be effective in lowering plasma cholesterol concentration by inhibiting the absorption of cholesterol in the small intestine. Phytosterols serve to stabilize phospholipid bilayers in plant cell membranes just as cholesterol does in animal cell membranes. The aim of this study was to isolate phytosterols from Hypoxis rigidula and evaluate its cholesterol reduction activity. The objectives were to extract phytosterols from Hypoxis using distillation; identify phytosterols using thin layer chromatography (TLC) and quantify phytosterols present in the plant extracts using high performance liquid chromatography (HPLC-UV). TLC gave the following phytosterol standard values: β-sitosterol at Rf 0.63±0, ergosterol at Rf 0.66±0 and stigmasterol at Rf 0.68±0. The chloroform extracts of both H. hemerocallidea and H. rigidula the presence of β-sitosterol, ergosterol and stigmasterol. HPLC analysis gave the following concentrations of phytosterols; 48.4 and 35.2 µg/ml of stigmasterol were found in H. rigidula and H. hemerocallidea respectively and 86.7 and 48.4 µg/ml of ergosterol were found in H. rigidula and H. hemerocallidea respectively. These results show a significant difference in the phytosterol content between the two species of the genus Hypoxis.Read Complete Article at ijSciences: V1201212111

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.

The aerial parts of Catharanthus roseus (C. roseus) plant have been known to contain many important alkaloids such as Vincristine, Vinblastine, Vindoline and Ajmalicine which are of interest to this study. Ajmalicine has also been found in abundance in the roots of this medicinal plant. The main objective of this study was to screen a methanolic extract of C. roseus for the presence of pharmaceutically valuable alkaloids using previously optimized conditions established in our laboratory set up.This methanolic extract was further purified for specific alkaloids present using modified Shams et al. (2009) method I extraction procedure. Extracts of C. roseus have been subjected to optimum conditions before and after Thin layer Chromatography which was performed in a trough chamber of 10 cm x 10 cm area saturated with Ethyl acetate: Benzene: Methanol: 25% Ammonia solution (100:5:5:3) as a developing solvent and sprayed with Cerium Ammonium Sulphate (CAS) reagent specific for the detection of alkaloids.Results have shown that the alkaloids of interest; Vincristine, Vinblastine, Vindoline and Ajmalicine could be chromatographically identified in extracts of C. roseus intact plant after individual alkaloid purification procedure. This has confirmed the anti-neoplastic and anti-hypertensive properties these alkaloids have in making the plant effective in healing cancer and high blood pressure as it was originally used by traditional people.Read Complete Article at ijSciences: V120121187

Mycotoxin contamination of feeds results in economic loss and transmission of toxins in the food chain. Animal feeds, the raw ingredients used in their manufacture, namely, maize, wheat, sunflower seeds, cottonseeds, bagasse, wheaten bran, gluten feed and pet foods from South Africa were surveyed for contaminating mycotoxin-producing fungi and their toxins: aflatoxins, fumonisins, zearalenone andochratoxins. Toxins were extracted and analysed by high performance liquid chromatography and fluorometry. Twenty-one of the twenty-three samples were contaminated by Aspergillus flavus which cooccurredwith A. parasiticus in two samples, A. tamarii in seven and Fusarium moniliforme in one. Rhizopus stolonifer, R. oryzae and yeast were also isolated. Aflatoxins were detected in seventeen samples, fumonisin in six and zearalenone in three. Aflatoxin levels ranged between 0.8 ± 0.2 and 156 ± 8 ìg/kg (ppb), zearalenone between 100 ± 10.5 and 165 000 ± 200 ìg/kg and fumonisin B1 between 15 ± 3.0 and 5 900 ± 40ìg/kg. Ochratoxins were not detected in any of the samples. In most countries worldwide, legislated levels for aflatoxins and patulin are 20 ìg/kg and 50 ìg/kg, respectively, for human foods. Fumonisins,zearalenone and other toxins are not legislated in most of the countries. Ten of the feeds contain toxin levels above legislated limits (for Canada and the USA) and guidelines set by other countries. The results ofthis study highlight the need for mycotoxin legislation in the animal feed industry.